EMBO goes East

Transcription

EMBO goes East

5/2015
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Editorial
5-2015
Lab Times
page 3
When Scanning Through…
Photo: www.publicdomainpictures.net/Kevin Casper
…the latest articles of the German newspaper Süddeutsche
Zeitung (SZ) and the French francetvinfo.fr, which denunciate the
disgusting and nasty habits of some producers and sellers of Fetal Calf Serum (FCS), the Lab Times editor experienced a peculiar
sense of déjà vu. The story sounded strangely familiar – and then
it hit him. Wasn’t there an almost identical story that appeared in
the German weekly news magazine, Spiegel, more than 20 years
ago? That’s right!
Searching the Spiegel archive, he had quickly dug up the old
article, dated January 25th, 1993. Under the heading “Science”,
the magazine, based in Hamburg, circumstantially reported on
the dubious practices in the FCS business (Spiegel 4/1993, pg.
190-3). In the introductory part of the article, it says:
“Every year, two million cattle fetuses are tapped for their
blood, to produce culture medium for GM technology and pharma industry. Serum procurement
is often controlled by traffickers and a slaughterhouse mafia.
‘Blood brokers’ sell unpurified,
possibly contaminated, products
from South America on the black
market.”
The Spiegel article from 1993
already mentions a certain Henner B. or Henner Brettschneider, who, as (former) owner of
the French serum producer, Biowest, headquartered close to the
north-west French town of Cholet, did his business with the help
of slaughterhouses in the Brittany and the Normandy, supported by German middlemen. And already back in 1993, the Spiegel
editors noticed there was something fishy about the Austrian serum seller, PAA, which was bought by GE Healthcare in 2011 and,
shortly after, turned out to be a serum adulterer. In Lab Times
6-2013, we reported on page 39 (“Undeclared Extras”) about the
company’s rise to stardom in the FCS scene and its recent crash.
Twenty years earlier, the Spiegel editors also had their doubts
about PAA’s integrity:
“The Austrian company, PAA, in Linz, is a typical example for
the inconsistencies in the serum business. In a newsletter, it offers serum batches of two tonnes each, originating from Hungary, ‘sterile-filtered, in plastic bottles’. It is, however, impossible for
Hungary (monthly yield: about 90 litres) to produce such enormous batches.”
The “current” revelations from the Süddeutsche Zeitung and
francetvinfo are nothing new – and that’s the real scandal. Thanks
to the Spiegel and Lab Times reports, everyone involved with Fetal
Calf Serum, including the scientists as serum ‘consumers’, must
have known for at least two decades, what goes on behind the
scenes of FCS production. Despite that knowledge, FCS usage increases year by year. Even the increasingly exorbitant prices over
recent years, do not appear to deter scientists from adding FCS to
their cell culture medium.
LT_515_03_03.indd 3
But likewise, for decades, suitable alternatives to FCS have
been in existance. The pioneers in the serum-free cell culture of
mammalian cells, David Barnes, Gordon Sato and Leonard Keay,
developed defined cell culture media back in the 1970s, already.
Almost ten years ago, the US-American stem cell expert, James
Thomson, and his group introduced a defined medium for culturing stem cells that contains merely eight essential ingredients and
that is now also commercially available. And Gerhard Gstraunthaler’s group in Innsbruck, Austria, has been experimenting
with human platelet lysate prepared from common platelet units
as a substitute for FCS for some time.
There are so many more examples for serum-free cell culture
media, if you only look for it. Perhaps you don’t even have to look
further than our latest product survey, which lists cell culture media from several producers (pg. 48). The portfolio of almost any
producer of cell culture media includes serum-free and/or chemically-defined media. Why then is
it so hard to forgo the beloved calf
serum and switch to serum-free
media?
The US-American science portal, Science Advisory Board, asked
377 bioscientists whether they
currently use serum-free cell culture media. Not less than 56 per
cent of the survey participants responded, Yes. As a reason, a quarter of the scientists said they do
not want components of animal
origin in their experimental set up. Another quarter said they use
serum-free media because they get more consistent results. Why
did the other 44% still rely on FCS-containing media? The three
most common reasons were: “difficulties adapting their cells to
the new medium” (40%), “high costs” (28%) and “lack of commercially available alternatives” (28%).
And how about you? Do you still use Fetal Calf Serum? Can
you do without FCS, or won‘t your cells grow without it? At least
since the latest revelations, it’s hard to keep on ignoring the facts.
The scientific community has to stand up to this topic and seriously look for ways out of the dependencies on shady profiteers.
This editorial also appeared in our German-language sister journal, Laborjournal.
04/09/2015 09:29
page 4
Lab Times
Contents
5-2015
News
Photo: www.mascarille.com
Picture of the issue / The future of genetics and genomics research / Mass retractions at Springer
and the Serbian Archives of Biological Sciences / Recently awarded / Digital technology
controversy / Singapore is first non-European EMBC Associate Member / Special arrangements
for refugees at German universities / Why rabbits are relatively immune to prion diseases_____ 6-13
Opinion
Observations of The Owl (56): Take Time to Think____________________________________ 14
Research letter from... Russia: When is Right to be Left?_______________________________ 16
Over the Line? (23): Swallowing the Ball__________________________________________ 17
Adding a few data points here, modifying
graphs there, Charles-Henri Lecellier prefers convenience. Even worse, his employers
seem to prefer convenience, too (p. 24).
Analysis
Cover Story
Ironically, even an accredited WADA antidoping laboratory seems to have major problems
in performing correct and reproducible doping analyses _______________________________ 18
Scientific Misconduct
Two friends don’t take Good Scientific Practice very seriously ___________________________ 24
Excellent research
Funders and politicians want more “excellent research”. But what does ‘excellence’ mean? _____ 28
Photo: Gergely Balázs
Journal Club
Helsinki/Finland Which factors drive brain evolution in threespine sticklebacks?___________ 32
Brno/Czech Republic Chromosome painting reveals the origin of Boechera species’ genomes__ 34
They look like jelly babies but these are formalin-fixed fish brains. Studying evolution,
Juha Merilä revealed that neural tissue does
not have severe genetic constraints (p. 32).
Publication Statistics
Cell biology research in Europe_________________________________________________ 36
What’s behind paper retractions? (30): Want to End Fake Peer Reviews? ___________________ 39
Biobusiness
Photo: Inge Matthies
News
Funding: CRISPR-Cas9 on the advance / FDA releases biosimilar naming guide______________ 40
Mitochondrial replacement therapy (MRT) under fire
The clinical introduction of MRT in the United Kingdom raises the question of whether we know
as much as necessary about MRT. Our Lab Times author argues that we don’t_______________ 42
Company portrait
The five-member start-up, Zetadec, located in the Dutch centre of life science and research, is
pursuing exceptional approaches for the food industry________________________________ 45
Service
Foto: American Chemical Society
Photo: Tobias Frygar
The Dutch company Zetadec assists their industrial clients in developing new foodstuffs,
as well as testing ingredients and propagating surprising new paths in nutrition (p. 45).
Product survey: Cell culture media_____________________________________________ 48
Methods
Tips and tricks of the trade: Quick, easy and cheap protein visualisation___________________ 55
Bench philosophy: Isothermal DNA amplification____________________________________ 56
New products _____________________________________________________________ 58
Book reviews
Grandmother Fish. A child’s first book of evolution. By Jonathan Tweet & Karen Lewis__________ 59
The Story of Everything. A pop-up book with pops, flaps and tabs. By Neal Layton____________ 59
Careers
Career strategies for young European scientists (LVI)
Quirky career paths (1): From cell biologist, via Nature editor to social studies of science _______ 60
Jobs____________________________________________________________________ 62
Calendar________________________________________________________________ 63
Researchers have developed various isothermal DNA amplification techniques, which
function significantly faster than PCR and
without expensive thermocyclers (p. 56).
LT_515_04_05.indd 4
Humour
Paul the Postdoc___________________________________________________________ 06
Contact__________________________________________________________________ 64
Laboratory Tales____________________________________________________________ 67
03.09.15 14:38
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03.09.15 14:38
Lab Times
News
5-2015
Picture of the issue
Through Ecologists’s Eyes
W
Photo: Mark Auliya/CC-BY 4.0
ho’s in danger? Counter-intuitively, it’s not the farmer
in the back but the Oriental Rat Snake (Ptyas mucosa)
in front. “Since the early 20th century, the species is involved in the international skin industry. In 1990 the species was
listed on Appendix II of CITES (Convention on International Trade
in Endangered Species of Fauna and Flora) that regulates trade by
an export permit, which is granted through the relevant management authorities. Particularly populations on Java (Indonesia) are
intensively harvested for their skins,” says Mark Auliya from the
Helmholtz Centre for Environmental Research in Leipzig, Germany. With this photo, he recently participated in an image competition, hosted by BMC Ecology. Even though he didn’t win, his photo
earned a “highly commended” seal of approval in the Need for Protection section. “The proximity of the snake to the person is nicely
demonstrated in this image, silently emphasizing even more the
vulnerability of this highly sought-after animal,” the judges ruled.
Held for the third time, the BMC Ecology Image Competition
was originally launched to showcase ecologists’ view of nature,
or in more flowery words: “Across the four oceans and seven continents, ecologists study the wondrous organisms, interactions
and locations that, combined, make up our own house, the planet Earth […] They are the connoisseurs of the beauty and mystery
of our natural surroundings, so who better to act as field guides
to show us our collective home.” This year, the judging panel had
to wade through over 200 image submissions. In the end, they
picked an image of “quiet beauty”, depicting a Palestinian sunbird
seeking nectar in a prickly thistle (Echinops sp.), to be the overall
winner. The image was taken by Mohamed Shebl from Suez Canal University Ismailia, Egypt.
-KG-
Paul the Postdoc
Even during The holidays...
LT_515_06_13.indd 6
Photo: Mohamed Shebl/CC-BY 4.0
page 6
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03/09/2015 13:09
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Lab Times
News
5-2015
Future of genetics and genomics
Predictive Power
Recently Awarded
It can be said with some certainty that more
than a few would give their right arm for a
glance into the future. Sadly, not even science can make this wish come true but it
at least allows some educated guesses. Recently, PLoS Biology invited eight experts in
genetics and genomics research to predict
where their discipline is going within the
next ten years (PLoS Biol, 13(7):e1002216).
Among the fortune-telling Eight are Ian
Dunham from the European Bioinformatics
Institute (EMBL-EBI), at Hinxton, UK; Peter Donnelly and Gil McVean, both at The
Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
Dunham, who, according to his website, has been “involved in genomics since
around the time the term was coined” muses about the challenges that must be overcome within the next decade. Methods
must be developed, he says, that “seamlessly connect” genome-wide data obtained
Honouring the “most creative and
productive stars in their field”, the
Boston-based Bert L and N Kuggie
Vallee Foundation picked three young
scientists from Europe to receive the
foundation’s 2015 Vallee Young Investigator Award. The lucky trio is: Martin
Jinek (University of Zürich, Switzerland),
Fabiana Perocchi (Ludwig Maximilian
University, Munich, Germany) and Rickhard Sandberg (Karolinska Institutet,
Stockholm, Sweden). Jinek studies the
CRISPR-Cas9 system, focussing on the
Cas9 part. With his research, he wants to
overcome current limitations of the system, when used as a genetic engineering
tool. Perocchi’s work revolves around
mitochondrial signal transduction cascades in health and disease. Amongst
others, she is interested in mitochondrial
calcium uptake. In Stockholm, Rickhard
Sandberg employs single-cell genomics
and bioinformatics to work out how gene
expression is regulated during early embryonic mouse development. The award
comes with a prize money of $250,000
(approx. €235,000), which is to be used
for basic research.
-KG-
LT_515_06_13.indd 8
Photo: www.publicdomainpictures.net/Junior Libby
His entire life, Enrico Coen from the
John Innes Centre, Norwich, UK, has
been “obsessed” with shapes and colours, of leaves and flowers that is. For
his work, he has now been awarded the
Croonian Medal from the UK’s Royal
Society that entails a lecture and a
gift of £10,000 (ca. €14,000). Coen’s
research involves a range of methods,
including microscopy, computational as
well as molecular biological approaches,
and model organisms (Arabidopsis,
Antirrhinum, Utricularia). With Arabidopsis, he, for instance, wants to decipher
the role of microtubules and nuclear
movements in the control of leaf cell
division and growth, to understand leaf
development better. Antirrhinum species
or dragon flowers are perfectly suited
to study the evolution of flower colour.
Therefore, Coen uses them to “identify
key genes controlling flower colour that
are under selection”.
tronic health data,” he predicts. This data
can then be used to answer complex genetic questions, like the consequences of a certain mutation on the carrier’s health or the
safety of a specific drug, in silico.
Last but not least, Gil McVean, who
specialises in statistical genetics and contributed to, for instance, the International
HapMap Project, shares his futuristic view
on big data. “The coming years will only
see the data rush grow: bigger samples,
new species, extinct species, data linked to
phenotype, temporal data, and so on.” We
shouldn’t, however, be afraid of the data
deluge coming upon us but take advantage
of it, to finally find answers for the big questions in evolution. Because these questions
can be best answered with a comparative
approach, he says. “What I’m looking forward to is, of course, more data. But this
time I don’t just want it from one (albeit
mildly interesting) species. I want it from
all of them,” McVean proclaims.
So, what can we expect from genetics
and genomics research in the next decade?
A lot more data, that’s for sure, but also answers to until now open scientific questions, which may even lead to medical advances. Or could it be, as corresponding author Chris Tyler-Smith from The Wellcome
Trust Sanger Institute, at Hinxton, points
out, that “the future will almost certainly
be stranger and, consequently, even more
exciting”?
Retractions at Springer and ABS
Summer Sort-Out
One doesn’t need to be a psychic to predict
the future of genetics and genomics research:
more data
from the likes of genome-wide association
studies (GWAS), chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing, to, for instance, cell-specific behaviours in health and disease. This would
“really bring biology in silico”.
Mathematician Peter Donnelly looks
into the future of clinical medicine. “The
cost of high-coverage whole human
genomes has plummeted to the point at
which this information is starting to be
collected as part of clinical medical care.
[…] Within 15 years, there may be one billion humans whose genomes have been sequenced, in many cases with links to elec-
In a new wave of setting the scientific record
right, two publishers recently flushed out a
host of papers that should never have been
published in the first place.
The first tsunami has its origin in Serbia. As Retraction Watch reported, the open
access journal Archives of Biological Sciences
(ABS), a multidisciplinary journal published
by the Serbian Biological Society, recently
retracted 16 articles and corrected two. An
internal investigation had made this cleanup operation necessary, which also included replacement of the entire editorial board.
“In the summer of 2014, the Archives of Biological Sciences was singled out as a scientific
journal that had veered away from the ethical publishing practice of scientific journals
and was placed on the list of predatory journals. Members of the scientific public in Serbia directly affected by the accusations were
mobilised, and after thorough investigation
it was concluded that many of these ac-
03/09/2015 13:09
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page 10
Lab Times
Photo: www.publicdom
ainpictures.net/Ge
orge Hodan
cusations were founded,” the new editorial team, led by Goran Poznanovic, from the
Institute of Biological Research in Belgrade,
wrote in an announcement in June.
The journal’s current issue features six
retractions; two had already appeared earlier this year, in issue 1. Behind the retractions is plagiarism, in most cases. Either
the authors had copied the entire paper (or
the majority of it) word for word or they reused data from an earlier publication without proper referencing. “The new editorial
team will continue to correct all mistakes
while striving to ensure accurate, timely, fair
and ethical publication of scientific papers
that the ABS has been traditionally known
for. We have invited all readers of the journal to directly contact the editorial office
to report cases of publishing malpractice,”
Poznanovic told Retraction Watch.
Plagiarism is not what caused a second tidal wave of retractions, this time at
Springer. Sixty-four articles in ten Springer
titles, including Molecular Neurobiology, Tumor Biology and Molecular Biology Reports,
were withdrawn from the scientific record
In the bin! More than 70 papers have recently
been disposed of by Springer and a Serbian
biology journal
for faked peer reviewing. “After a thorough
investigation we have strong reason to believe that the peer review process on these
64 articles was compromised. We reported
this to the Committee on Publishing Ethics
(COPE) immediately,” the publisher said in
a statement.
This scam to manipulate the peer review process seems to be on the increase in
recent times. Not long ago, BioMed Central
had to pull more than 40 articles after realising that “some author-suggested reviewers appeared to be fabricated”. But publish-
LT_515_06_13.indd 10
News
5-2015
ers have been sensitised and are ready to
take action. “The peer-review process is one
of the cornerstones of quality, integrity and
reproducibility in research, and we take our
responsibilities as its guardians seriously.
We are now reviewing our editorial processes across Springer to guard against this kind
of manipulation of the peer review process
in future,” the publishing house assures.
Digital technology controversy
Solid Base
Can Facebook trigger autism in young people? Or do computer games make us more
aggressive? Does Google make us dumb?
The answer to all those questions is yes
– that is, if you buy into the claims made
in the 2014 popular science book, Mind
Change, by British neurophysiologist, Susan Greenfield.
Through appearances and interviews,
Greenfield has promoted her views extensively but now three researchers counter
her claims in an editorial for BMJ, asking
Greenfield to adhere to the scientific method and publish her hypotheses in peer-reviewed journals. “As scientists working in
mental health, developmental neuropsychology, and the psychological impact of
digital technology, we are concerned that
Greenfield’s claims are not based on a fair
scientific appraisal of the evidence, often
confuse correlation for causation, give undue weight to anecdote and poor quality studies, and are misleading to parents
and the public at large,” write Vaughan
Bell (University College London), Dorothy
Bishop (University of Oxford) and Andrew
Przybylski (University of Oxford).
To prove their point, the three scientists,
amongst others, cite research, showing the
exact opposite of Greenfield’s claims to be
true. Thus, playing action video games has
been shown to have a positive effect on the
neuropsychological performance, for instance. Replying in the Australian, Greenfield clarifies: “I have never suggested that
reasonable use of the internet damages the
adolescent brain.[…] However, intense use
of the internet and video games does indeed lead to changes in the physical brain
comparable to drug abuse”.
Obviously, any claim made in public
should be based on solid scientific studies. In her book, however, Greenfield had
to “synthesise the literature in a meaningful way that would be accessible to the general reader”. The three researchers, writing in BMJ, think otherwise. “There is al-
ready much research into the many concerns about digital technology, and the public deserves to participate in the debate fully
informed of all the evidence.”
Singapore becomes EMBC member state
EMBO goes East
For some, it’s the perfect holiday destination, for others, Singapore provides all the
amenities for a happy and successful researcher life – great infrastructure, good
atmosphere and generous funding (see also
LT 3-2013 and 4-2013). And the investment
in research has certainly paid off. Our own
publication analysis, for instance, consistently lists the Southeast Asian city-state as
one of the best when it comes to citations
per article, in a wide range of research disciplines.
Reason enough, to take advantage of all
the expertise, thought the European Molecular Biology Organization (EMBO) and
its funding body, the European Molecular Biology Conference (EMBC). Recently,
they made Singapore the very first EMBC
Associate Member State. “We are extremely pleased to welcome Singapore as the first
EMBC Associate Member State. Since it was
founded, EMBO has viewed cross-country
cooperation as an essential foundation for
the growth of science. The scientific community in Singapore, with its strengths in
research and technology development, is a
perfect partner for the exchange of expertise and we look forward to further collaboration in the years ahead,” EMBO director,
Maria Leptin, said in a press release.
The agreement between the government of Singapore (represented by the
Agency for Science Technology and Research, A*STAR) and EMBO will come into
effect at the beginning of next year and is
scheduled to run for three years. Building
on an earlier agreement, signed in 2011,
that allowed scientists based in Singapore
to apply for EMBO Short-Term and LongTerm Fellowships as well as the EMBO
Young Investigator Programme, the cooperation has now been renewed and intensified: Singapore scientists can still apply for
Fellowships and one group leader per year
is eligible to join the EMBO Young Investigator Network. Other activities include:
Funding for an EMBO workshop in Singapore, support for keynote lectures given by
EMBO members at conferences in Singapore and travel stipends to attend EMBO
courses and workshops, and the EMBO
meeting in Europe. Scientists based in
03/09/2015 13:09
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Lab Times
News
5-2015
Europe can, in turn, apply for financial support to attend EMBO workshops in Singapore. The next one, on “Telomeric chromatin and telomere fragility”, for instance,
takes place at Nanyang Technological University, between December 7th and 10th.
“We are confident that this agreement
will spur international collaborations in
world-class scientific research, which will
pave the way for new biomedical discoveries and global healthcare solutions”,
Lim Chuan Poh, Chairman of Singapore’s
A*STAR is certain.
Help for refugees at German universities
University Support
Hardly a day passes without news that another non-seaworthy boat full of people,
in desperate search for a better life in Europe, has crossed the Mediterranean Sea.
According to the UNHCR, the UN refugee
agency, more than 100,000 people, mainly
from Syria, Afghanistan and Iraq, have ar-
rived on Italian, Greek, Maltese and Spanish shores in 2015, to-date. Although university access might not be the first thing
on the refugees’ minds, after arriving in
Europe, in the long run, academic training
might be key to making the dream of a better life come true.
Setting a good example, German universities started to make special arrangements for refugees and migrants, wanting to study in Germany. In August, for instance, the Saarland University announced,
refugees and migrants who don’t have proof
of their university entrance qualification,
can still enrol in STEM courses like systems
engineering and informatics by simply passing a qualifying examination and a German
language course. “With this programme, we
want to create a non-bureaucratic access for
refugees, to give these talented young people a bright future in Germany,” said university president Volker Linneweber in a press
release. Other activities at German universities include financial help, waiver of semester fees, psychosocial support, information
Y
events, legal advice, help to find accommodation and free rides in buses and trams.
A recent survey by the German Rector’s Conference (HRK), the political and
public voice of universities in Germany, revealed that more than 60 of the country’s
universities had such arrangements. Especially many activities are at the Universities
in Bremen, Erlangen, Hildesheim, Ulm, Hohenheim and Munich, according to the HRK
press office.
“We are concerned to see that people
are reacting with uncertainty to the influx
of refugees and that in some places xenophobia is increasing. Through activities
like these, universities are making an important contribution to the social integration of refugees and sending out a signal
for an open, forward-looking society,” said
Horst Hippler, HRK president in a press release. “I would like to encourage universities to make full use of the scope allowed
by law to offer refugees encouraging prospects”, Hippler added.
-KG-
Carrot-Nibbler Offers Resistance
Rabbits are relatively immune to prion infections. French scientists wanted to know why.
Vincent Beringue from INRA Virologie Immunologie Moléculaires,
Jouy-en-Josas, France, and colleagues tried to answer that question
by creating transgenic rabbits, expressing a scrapie-susceptible ovine
PRNP allele of the PRNP gene (encoding the PrP protein)
on a rabbit wildtype PRNP background (PLoS Pathog,
11(8): e1005077). Then they exposed their test subjects to sheep prions via intracerebral inoculation and
waited half a year. All animals with the sheep transgene
showed clear signs of TSEs (PrP deposition and vacuolation in the brain, vision loss, loss of balance, disordered
gait, etc); the control wildtypes, however, stayed healthy.
“This demonstrates that rabbits do not bear non-PrP
factors that make them intrinsically resistant to prions,”
Sarradin et al. concluded.
When analysing the brains of infected rabbits closer,
the scientists found only ovine PrPSc’s. This finding made
the scientists hypothesise that the sinister transformation of normal PrPC to sickening PrPSc perhaps just takes
a bit longer. They assume that the conversion rate of rabbit PrPC is
very low.
Summing up, Beringue and colleagues have come to realise that
neither “rabbit genetic background and rabbit PrPC (can) explain the
apparently low susceptibility of rabbits to prion infection. What makes
the rabbit species comparatively resistant to prion disease remains to
be clarified”.
So, for now, the little furballs can keep their secret.
Photo: www.publicdomainpictures.net/Jamie Hutt
P
rions – six letters that send a frightful fear down many peoples’
spines. These proteinaceous pathogens are believed to be triggers of, for instance, mad cow disease, scrapie (in sheep and
goats) and Creutzfeld-Jakob disease in humans
– all of them fatal neurodegenerative diseases,
collectively known as transmissible spongiform
encephalopathies, TSEs.
On the molecular level, prions are nothing other than misfolded isoforms of the natural-occurring
prion protein, PrP. Strangely, the abnormal form
(PrPSc) somehow “coaxes” the normally folded
protein (PrPC) to follow suit and fold wrongly, leading to protein accumulations and, eventually, cell
death. PrPC’s normal function in neurons is still in
the unknown; some studies, however, suggest that
it binds copper and could be involved with copper
sequestration and internalisation or protection
against oxidants.
Many mammals can fall ill from TSEs but there’s one tiny creature
that seems to somehow defy the odds: the rabbit. For many decades,
scientists tried to transmit Kuru, Creutzfeld-Jakob disease or sheep
scrapie; alas, with little success. Rabbits were thought to be a prionresistant species. Only three years ago, an international team of
researchers proved the dogma to be wrong (PNAS, 109(13):5080-5).
“Despite rabbits no longer being able to be classified as resistant to
TSEs, an outbreak of ‘mad rabbit disease’ is unlikely,” the authors
commented, as quite some effort was needed for that result. So, what
makes rabbits “relatively resistant” to prion infection?
-KG-
(More research results from European labs on pp. 32-35)
G
B
F
U
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03/09/2015 13:09
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LT_515_06_13.indd 13
03/09/2015 13:09
page 14
Lab Times
5-2015
Opinion
Observations of the Owl (56)
Take Time to Think
N
o doubt about it, science
needed – which most of the time is reeeeally monotonous work.
needs heroes. Oh, yes – I
No wonder, therefore, that Bushtit inevitably started thinking
can virtually see how many
about his “problem”, while endlessly flying back and forth to the
of you immediately wrinkle your
nest. And once he had finally realised that something must be funbeaks and noses upon that asserdamentally wrong with his extraction strategy (around flight no.
tion. But don’t you think it’s simply
820), it wasn’t much longer before his brain identified the “error”
appropriate to honour and praise
(around flight no. 900) and produced the solution (around flight
those, to whom we owe some of
no. 980). Only a couple of weeks later, Bushtit proudly presented
the most important insights into
the long-sought moulting factor to the scientific bird world.
our world and lives? Regardless of
Nice little anecdotes, aren’t they? Did you notice something?
their sometimes admittedly... well,
Perhaps some kind of common pattern? Yes, that was easy: all
special characters.
three developed their critical breakthroughs or had their eureka
A more important point, however, is that in this way they can
moments, while primarily engaged in completely different activiserve as pretty good role models – at least as far as the ways of deties – somewhat boringly monotonous activities, in fact.
veloping really great ideas are concerned. Even if I might risk borMany say that monotonous and largely mindless activities
ing the feathers off my winged colleagues, let me tell you three
can trigger your brain to fly to unknown heights. But I don’t think
exemplary stories of eminent “heroes” in our avian life sciences...
that this is the crucial point here. Actually, most of the practiFirst of all, there is famous Professor Sandpiper, who, decades
cal laboratory work is extremely monotonous – and be honest, is
ago, discovered how, by applying an inner compass, the brains of
your brain flying particularly high when pipetting hundreds and
my migratory fellows build up a mental map and use it to precisethousands of probes over days and weeks?
ly navigate their marathon flights over several thousand kilomeI think what’s more important, is that you simultaneously
tres to their final destination. And guess when she developed the
take a step back from your currently pestering but often deadkey idea and concept, which finally led to the experimental revelocked problem. And by gaining some distance you may suddenly
lation of the whole process? Exactly! During one of her seemingly
get a clearer and broader view, allowing you a deep new insight
never-ending flights to her southern-winter domicile. “Aside from
into the question from different and hitherto neglected angles.
navigating, there were obviously still some free neurons in my
At least, this is what obviously happened to Sandpiper, Kiwi
brain for thinking – and believe me during the flight I had plenty
and Bushtit. And fortunately, every bird scientist will always find
of time to do exactly that,” was one of her famous quotes.
time to step back and take a new look at their problem(s), since
Then there is the grand old man of bird immunology, Proover and again, as in the examples above, our ornithological nafessor Kiwi. He belonged to a Kiwi species, where incubating
ture leaves us no other choice than to let go of them for a while.
the eggs is solely the male’s job – for a reThe same is apparently not true for you hucord-breaking period of up to 90 days! A peri“The whole theory was hatched mans. I remember a conversation on this isod leaving no time at all to put claw, beak and
and developed while doing noth- sue with my human friend Renaldo, in which
wing to any experiment, logically. This, howing other than sitting on an egg.” he quite angrily ranted about an article in your
ever, doesn’t necessarily mean that this time
Nature magazine. Over three pages, the article
is completely void of science. Kiwi proved this in a most imprespretty much lauded a certain researcher for demanding that his
sive way. One year, when his offspring had freshly hatched, he
PhDs and postdocs spend more than 120 hours over seven days
stepped out of his breeding burrow, spread his wing-stumps and
per week in the lab – as he was doing himself, of course. What a
triumphantly said, “I think I now know how our immune system
load of chicken shit! Fortunately, this is not every PI’s maxim. Reactually manages to produce and coordinate those myriads of difnaldo continued to tell me about a wise and considerate research
ferent, highly specific antibodies.” So, what has since gone into
director who, instead, advised his
our textbooks as the “select and link theory” of the avian immune
students to always try schedulsystem was actually hatched (scuse the pun) and developed while
ing their experiments, so that they
doing nothing other than sitting on an egg.
have the weekends free to do someAnd, lastly, there is the story of Bushtit. He was still a postdoc
thing completely different. In fact,
when, one spring long ago, he desperately tried to extract and
that was how he had been handling
identify a certain molecule, which he suspected to operate as the
it ever since his own PhD. And this
key signal for starting the regular feather moult. For weeks, his
specific guy, Renaldo emphasised,
experiments brought no results – but with each failed extraction,
as the final icing on the cake, had
he grimly attacked the next one with even more grit and determieven won a heroic Nobel Prize for
nation. Until one day, when from one moment to the next, he was
his postdoc work.
forced to halt his experiments completely – no longer could he esSo, who is the better role modcape his hormones, which were screaming at him to start building
el: This noble “hero” or Mr. Chicka nest right now. Well, I should mention that bushtits build very
en-Shit?
complex nests; it takes weeks alone just to collect all the materials
Comments: [email protected]
LT_515_owl.indd 14
03.09.15 15:13
*onlLianb Times is also availab
le as e-pa
e or offlin
per for
e
r
e
a
ding on yo
tablet, no
ur compu
tebook or
ter,
smartpho
ne – it’s f
ree!
LT_515_15_15.indd 1
07.09.15 13:19
page 16
Lab Times
Opinion
5-2015
Research Letter from:… Russia
When is Right to be Left?
By our corresponding author, Kakiye Storony
M
ost humans are right-handed – they favour their right
hand over their left when doing things. But why? The
origins and significance of handedness in humans are
unclear but theories and ‘studies’ are in abundance (as shown
in the Wikipedia entry on ‘Handedness’). Now, however, a
group of Russian researchers claim to have obtained the first
demonstration ‘at the population level’ of handedness in animals, other than humans.
In their recent article, Andrey Giljov et al. see a “Parallel
Emergence of True Handedness in the Evolution of Marsupials
and Placentals” (Curr Biol, 25(14):1878-84). Observing seven
species of marsupial in zoos and nature reserves, they looked at
how these animals use their ‘forelimbs’ and found that two species of kangaroo (eastern grey and red) are ‘left-handed’, preferentially using their left forelimbs.
But what does this mean, biologically? For a decade, the research group at Saint Petersburg State University has been navigating its way across the animal kingdom in a search for examples of ‘laterality’ – the preferential use of one side of the body over
the other.
Lateral speculations
Photo: www.publicdomianpictures.net/Lilla Frerichs
In their study of fish, ‘Eye as a
key element of lateralized response
in fish’ (Anim Cogn, 16(2), 287–300)
Giljov had fish swim through a perspex tank, in which images of other
fish were displayed to the left or right
(or they saw themselves in a mirror).
These pond-living fish (Perccottus
glenii) apparently preferred looking
at other fish (or their own reflection)
with their left eye, although it is not
explained how this might work when
two fish are swimming side-by-side – if you’re on my left, aren’t
I on your right? Nevertheless, Giljov speculates that there must
be a lateralised social response if the fish are showing “a significant left-eye preference for the inspection of social stimuli”.
This idea is extended to whales – a tendency to swim on
one side of a fellow whale must reflect “social” tendencies in
the other brain hemisphere. In ‘Visual laterality of calf-mother interactions in wild whales’ (PLoS ONE, 5(11):e13787), baby
beluga whales were seen to preferentially swim to the right of
their mothers, i.e. on the baby’s left-side. Based on theories of
handedness and brain crossover in humans, Giljov speculates
that this is due to “right-hemispheric advantages in social responses”. Similarly in killer whales (orcas), the lateral bias in
mother-infant pairs was “assumed to be caused by calves’ rightbrain hemisphere specialisation for social processing” (Anim
Behav, 86(6),1225–31).
Throughout, there is also an undercurrent of evolutionary theory. For example, they seek to establish when laterali-
LT_515_16_17.indd 16
ty first appeared in evolutionary history. In their study, ‘An eye
for a worm’, they compared the lateralisation of feeding behaviour in species of fish, frog and newt (Laterality, 14(3), 273–
86). The fish and the newt both showed right-eyed preferences when inspecting food items. Meanwhile, the frog had a balanced vision of its food and displayed no laterality. Clearly, Giljov says, these results “extend our knowledge of lateralisation
in the visual system of vertebrates and allow speculation on its
evolutionary history”. In fact, by plotting their fish/frog/newt
onto the evolutionary map, they claim to have dated back the
history of visual laterality in vertebrates to the Devonian Period
(over 350 million years ago)!
Human-kangaroo parallel universe?
In this latest study, Giljov et al. find that certain kangaroos
have a consistent left-forelimb bias when grooming, feeding,
or propping themselves up. This discovery of ‘left-handedness’
in kangaroos leads to even more evolutionary speculation – the
results “challenge the traditional belief in the evolutionary uniqueness of
human handedness”. They even told
BBC News (18/06/15) that this confirmed that “we are not alone in the
Universe; we are two – humans and
kangaroos”!
Furthermore, this must be ‘parallel evolution’ because handedness
is observed in two separate branches
of the ‘evolutionary tree’ – primates
(placental mammals) and kangaroos
(marsupials) – but not in related animals between them. Posture is the
major factor, says Giljov, pointing to
the ‘postural origins’ theory for primates, in which the transition from
an arboreal lifestyle favoured the emergence of functional specialisations of the left and right hands. Giljov claims to have
found similar differences between arboreal marsupials – which
walk on four legs – and the terrestrial species that stand upright on their hind legs and use their forelimbs for tasks other
than walking.
All of which continues to justify even more speculation
about the underlying meaning, for example, for neuroscience.
The article’s press release says its findings will “encourage
more careful study of the marsupial brain” because there are
links between human neurological disorders and handedness.
Such studies of ‘left-handed’ marsupials might “yield important
insight into neuropsychiatric conditions, including schizophrenia and autism”!
Presumably, the next step will see Giljov trying to get marsupial brain scans using magnetic resonance imagery (MRI).
Now that could generate lots of lateral data, not least from trying to force the kangaroos into the scanner.
03/09/2015 13:14
Opinion
5-2015
Lab Times
page 17
Swallowing the Ball
N
ero,
One Swallow does not make a summer. Rather, a
swallow followed by rain, to the power of three months, makes a
British summer. This uncertainty has a profound impact on our
summer sporting rhythm. Here, I refer to Cricket, the nation’s defining summer pursuit, rather than the chirping relative of the
grass hopper.
Our meteorological uncertainties meant that early cricketers needed to set aside five full days for a single game. I know
you are a big fan of the bat and ball game and the sight of a player from one team projecting a red leather-clad ball at an opponent 22 yards away. This projectile aimed at a mock-up privet
fence or “wicket” is at the game’s heart.
The integrity of the wicket is guarded by
Over the Line?
a man holding a bat, who should swot
the ball away. The batsman can then run
the 22 yards to a wicket precisely aligned
at the opposing end and, if he does this
before the ball is returned to the wicket, he scores a run. Should the batsman
miss the ball and the bowler is accurate
Dispatches from the
enough to hit the wicket, the batsman is
borderlands of science
out. Similarly, if the ball is hit into the air
and a colleague of the bowler, a fielder,
catches the ball before it hits terra firma, the batsman is out.
A team has eleven players and the batting team is dismissed
when 10 batsmen are out. The batsmen then become the bowlers. This is all played out by gentlemanly folk, dressed in white.
A full game, weather permitting, will see each team bat and bowl
twice. Brutality, strength and aggression can work but this belies the fact that exquisite timing can ensure heroic batting. The
games subtleties extend to the fine art of bowling, as dexterous
manipulation of the ball’s trajectory by skilled bowlers can deceive batsmen and trick them to mistime or miss the ball completely. One can expect a team to deliver up to 600 bowls in a day
and these deliveries are packaged up into small portions of six,
called ‘overs’. This produces a game with the kind of ebb and flow
that makes tidal rhythm seem frenetic. Indeed, when dovetailed
with British weather, the game’s rules seem designed to provide a
sporting strategy, in which the result is an honourable but always
a well-fought draw.
Bio-rhythms
I often feel cricket has parallels with the slow increments,
upon which science is really played out. Rarely with the ‘biff bang
bosh’ of rapid endgame. Rather, the slow considered progress reflected in the preferred, densely documented reporting of a pre1970s’ submission to the learned society journals. Abstracts were
precise, introductions historic, material and methods exhaustive,
and discussion addressed events in their entirety. This displayed
science as it is, rather than in the form of the 15-minute highlight package that distorts the drama, or lack of, when immersing
oneself in a full day’s play. Not to say light bulb moments were
not possible in these more sober scientific times. However, bouts
LT_515_16_17.indd 17
of scientific pursuit that broke the mould of a more sedate increase in iterative understanding were just rare and normally recognised retrospectively, not currently. These moments are all the
more uplifting when they are unexpected and particularly exciting when they reward a previously put-upon colleague, who goes
on to undermine the certainties of a mortal enemy.
Resurrection from the Ashes
This summer saw the rains and a visit from Ingerland’s mortal enemies. Cricket has a global reach that shadows the British
interest that the sun never set on. Foremost, among the cricketing nations are the ancestors of the Banished, sent “Down Under”
in the 1700s for heinous crimes, like stealing bread. These displaced petty criminals have grown into a
mongrel race in the penal colony that became Entrailia. Here, they nurtured uncultured cricketing traditions, like winning. Indeed, they set about bastardising
the game into a villainous truncated pursuit that involved dressing in pyjamas and
playing for half an afternoon or with a
white ball at night. Outrageous! No time
for a swift aperitif, let alone lunch and
tea. These bastardised forms of purity resonate the modern scientific preference for
punchy papers, with pithy titles and “clear messages” and, horror
upon horror, no or hidden methods sections.
Ingerlish cricket played at 19th century pace just could not
compete and our penal cousins arrived having thrashed us most
recently by five matches to nil (a whitewash). Indeed, we expected a disaster as great as the first defeat we suffered at the
hands of the visiting robbers in 1882. This led to the wicket being burnt and stored in an urn to symbolise the death of English (and by inference) civilised cricket. Oh a summer of humiliation was the expectation, so good and cocksure were our penal cousins that not even the weather could intervene to win us
a few draws. But to the cries of ROOOOOOOOOOOOOOOOOT!
ROOOOOOOOOOOOOOOOT! and B-ROAD, we enjoyed a renaissance. Our saviours, Joe Root and Stuart Broad had been mentally bombarded by the Entrailians – both on the pitch and in the
terraces. Their crime was to be prettier and more “bantiful” than
their dull-head opponents (http://tinyurl.com/nq2ls3a). Despite
these onslaughts, these fine young men (as they are known to
their mothers) stood tall, and batted and bowled with such abandon that the Entrailians were toasted. Ingerlish cricket, traditionally built on the considered pace that allowed it to fill a five-day
pursuit, was transformed. Yes, the summer was full of unexpected light bulb moments. Root’s batting and Broad’s bowling delivered victory with all the panache and certainty of a 1,000 word
Nature news and views.
Nero, I think I can see a swallow holding an umbrella, must
mean rain. No problem! The cricket’s over and the Ashes are regained. Who needs a methods section when victory is ours?
Yours in ROOOOOOOOOOOOOOOOOOOOOOT.
FintaN O’Toole
03/09/2015 13:14
page 18
Lab Times
Analysis
5-2015
When the Rome-based, WADA-accredited anti-doping laboratory tested the
race walker Erik Tysse (photo) for
misuse of rEPO, good repeatability
was definitely not achieved
Problems at a WADA-accredited anti-doping lab
Puzzling
Discrepancy
Photo: private
Doping tests are very important to ensure fair competition but the test results should, of course, be correct and
above doubt. Ironically, an accredited WADA laboratory
seems to have major problems with the latter.
A
noteworthy article by Garribba and co-authors, all at the
World Anti-Doping Agency (WADA)-accredited laboratory in Rome, appeared in the June 2014 issue of Bioanalysis (6(12), 1605–15).
This article, entitled, A modified procedure based on a vacuum-driven blotting system for the detection of erythropoietin and its
analogs, is not only noteworthy due to errors and an inaccurate
presentation of results but also because the presentation is made
by a professional and WADA-accredited analytical laboratory. It is
disturbing that sloppiness and errors can dramatically influence
the life and career of athletes, when tested for performance-enhancing drugs by this laboratory. We have earlier demonstrated
(Nissen-Meyer et al., Weak Evidence. Lab Times 1/2013, pages 18–
23) and will give further evidence here that these concerns must
be addressed.
Detecting erythropoietin in urine
In their study, Garribba and co-authors examined the specificity and repeatability of WADA-approved methods – and slightly
modified versions of these methods – for detecting recombinant
erythropoietins (rEPOs) in urine. The amounts of rEPO in rEPOspiked urine samples were measured and mean values, standard
deviations (SD), and coefficient of variation (CV%) were reported. The authors concluded that the methods for detecting rEPOs
I n fo rm a t io n b ox : S a me u r i n e s a mp l e b ut different results
The adjacent Figure 1 shows three analyses for the presence
of rEPOs in Erik Tysse’s urine sample. The results are from the
laboratory’s documentation that was presented at the Court of
Arbitration for Sports (see source below). The athlete's A-sample was tested three times using isoelectric focusing (IEF) and
double-immuno-blotting.
We [the Lab Times authors] have cut out the athlete's lanes
from the three IEF gels and placed the lanes side-by-side
in order to more easily compare the results. The same urine
sample was used in these three analyses, and the same concentrated urine sample was used in the first and second test
(i.e. the samples applied to the gel were taken from the very
same test tube).
Source: Laboratorio Antidoping–FMSI, Documentation Package Sample A code 3511158 (www.eriktysse.com/Dockuments/The%20report%20for%20the%20A-sample.pdf)
LT_515_Doping_part_2.indd 18
Figure 1
03.09.15 12:37
Analysis
5-2015
Lab Times
page 19
have good repeatability, specificity and accuracy and are consequently reliable.
Ironically, that conclusion is undermined by inconsistencies
and mistakes in many of the numerical results presented to support the conclusion; there are, in fact, obvious and serious mistakes in five of the eight datasets shown for rEPO in the article’s
main table (their Table 1).
For instance, a mean value for the amount of rEPO is presented as 14,179,217 with an SD of 71,58,031 and a CV of 9%.
Aside from the use of too many significant digits and the unconventional and confusing use of commas in the SD, at least one of
these numbers must be wrong; 7.1 million is 50% of 14.1 million,
not 9%. In this case the SD value is wrong.
An SD with exactly the same numerical value also appears in
a completely different dataset in Table 2; the SD has most likely been “copied and pasted” from Table 2 to Table 1. The exact same mistake is encountered in the next dataset in Table 1,
where the SD value (presented as 18,40,893) is wrong. This SD
has also been erroneously copied and transferred from Table 2.
For another dataset in Table 1, it is the mean value for the
amount of rEPO (presented as 198,886,367 with an SD of
3,783,711) that is wrong; it is 10 times too large and should −
judging from the electrophoresis data − be about 20 million.
5-2015
Lab Times
page 19
Biometra TRIo
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Serious mistakes in five out of eight datasets…
One might think that this is not so serious. After one of us
(JNM) made the editor aware of the mistakes, a correction appeared in May 2015 (issue 9) of Bioanalysis and corrections have
now also been made in the electronic version of the relevant Garribba et al. article. It should be noted that there is no information
in the new version that changes have been made; as the original
version has been removed from the website, the numbers we refer to above can only be found in copies taken before the corrections were performed.
But why are we worried about these mistakes? Are we being too picky, considering that the mistakes and inconsistencies
are so obvious that a reader can, at a glance, identify and correct them?
No. We rather find it is worrisome that these obvious inconsistencies and mistakes were not identified by any of the six authors,
all working at a professional and WADA-accredited analytical laboratory that each year tests thousands of athletes for doping.
… not identified by any of the six authors
The good repeatability reported in the article was definitely
not achieved when this Rome-based, WADA-accredited laboratory tested the race walker Erik Tysse for misuse of rEPO (see the
adjacent information box and Lab Times 1/2013, pages 18-23, for
details about the Tysse case).
This information box (see opposite page 18) shows the results of three repeated tests of Tysse’s A-sample urine. Four of
the six authors of the Bioanalysis article were involved in this test
and they reported it as positive for CERA (a form of rEPO). The
first test (first lane in Figure 1) is the one that most clearly reveals the athlete’s normal endogenous EPO, whereas the bands
in the CERA region are not clear (see Lab Times 1/2013, page
18ff, regarding interpretation of bands in the CERA region).
The second test (second lane in Figure 1) reveals a large and
unexplainable amount of material in the CERA region. Remarkably, the samples used in the first and second tests were from
the very same test tube and the experiments were car-
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03.09.15 12:37
Lab Times
Analysis
5-2015
Photo: WAADS
page 20
Francesco Botrè was president of the World Association of Anti-Doping
Scientists (WAADS) from 2006 to 2008 and is the acting Scientific Director of the WADA-accredited Laboratorio Antidoping FMSI, located in
Rome, Italy. It is his laboratory that performed the analyses described
in the article.
The Laboratorio Antidoping FMSI A-sample
report from June 2010.
On page 22 (top right)
you can see black rectangles hiding information about sample numbers; similarly on page
38 (bottom right) for the retesting of samples. We [the authors] believe that the 'R' after the sample number for Tysse (A4433) on this
page means 'retesting'. Why are the other sample numbers hidden?
No need for secrecy if everything is OK because you need the code to
deduce from whom the urine samples were obtained.
ried out in the same manner. The two results should, therefore,
have been identical. In the third test of the same urine sample
(third lane in Figure 1, page 18), hardly any of the athlete’s normal endogenous EPO was detected but the relative amount in
the CERA region had increased even further, resulting in an extraordinary 400-fold increase in the relative amount of CERA
from the first to the third test. Considering how poorly CERA is
secreted to urine, the results of the third test indicate an unrealistic amount of CERA in the urine; they imply a concentration of
CERA in Tysse’s blood that is almost 10,000 times greater than
the concentration of his natural EPO.
The discrepancy is simply too large
The results shown in Figure 1 (page 18) do not fulfill WADA’s
own stability criteria, which say that the distributions of the
most intense bands appearing in the initial testing procedure
(i.e. the first and second test in Figure 1) and confirmation testing procedure (i.e. the third test in Figure 1) should be similar
[WADA Technical Document – TD2009EPO]. It is indeed difficult to imagine that one and the same urine sample should give
the results shown in Figure 1; the discrepancy between the tests
is simply too large.
No one has been able to explain this discrepancy. At the Court
of Arbitration for Sport (CAS), representatives from WADA-accredited laboratories stated that this lack of reproducibility might
have been due to a contamination in the first test and that the
discrepancy, regardless of cause, does not really matter:
“… it cannot be excluded that lane 3 [the athlete’s sample
lane] was contaminated with retentates from the neighbouring
Ba c k g ro u n d : T h e d o p i n g c a se s a g a i n st Er ik Ty sse and Alex Sc hwazer
Re-Analysis by Another Laboratory Rejected
The Norwegian athlete Erik Tysse participated in a race-walking
competition in Sesto San Giovanni, Italy, in May 2010. Tysse
came in second, after the Italian race-walker Alex Schwazer.
Schwazer is well-known for winning the Olympic gold medal in
race-walking in 2008 and for testing positive for rEPO before the
Olympic Games in 2012. Subsequent investigations by Italian
authorities indicate that he also used performance-enhancing
agents before 2012 and that officials for athletic organisations
might have been aware of this (see article in The New York Times:
http://mobile.nytimes.com/2013/06/19/sports/olympics/
officials-accused-of-covering-up-italian-olympians-doping.html).
Schwazer also used the Italian “doping-doctor” Michelle Ferrari as a “training-consultant” (as did cycling professional, Lance
Armstrong) and, in fact, contacted Ferrari immediately after the
competition in Sesto San Giovanni in 2010.
Urine samples from six athletes − among these were Tysse
and Schwazer − who participated in the competition in Sesto San
Giovanni were sent to WADA’s laboratory in Rome. The laboratory
reported the presence of CERA in Tysse’s urine; he denied use of
CERA and asked for his urine to be re-analysed at another WADA
laboratory but the request was rejected.
Screening tests indicated that the urine of another athlete
also contained rEPO, however, this was not reported by the
laboratory as an adverse finding because the signal in the following confirmation test, which was run on the same gel as Tysse’s
confirmation test, was reported to be not good enough. Judging
from the band-tailing and streaking that was obtained in this test,
it appears that the sample was either destroyed after the initial
screening test (which was positive) or that it was inadequately
applied to the gel.
03.09.15 12:37
Analysis
5-2015
lane... In any case, due to quality issues, the data from the first
screening [i.e. the first test shown in Figure 1] was not accepted by the laboratory and the IEF analysis was repeated from the
same retentate. Consequently, the data from this initial screening [i.e. the first test shown in Figure 1] was nullified and the
data from the second screening [i.e. the second test shown in
Figure 1] was considered as the valid data for assessment purposes.”
[a quote from Expert Opinion given by Günter Gmeiner, Laboratory Director, WADA-accredited Doping Control Laboratory,
Seibersdorf, Austria].
Same urine, different results
It is not at all clear to us how contamination of the first test is
compatible with the results shown in Figure 1. If contamination
did in fact cause the discrepancy, it must instead have been the
second and third tests that were contaminated.
Also, it is not clear to us why the first test should be “nullified”. Of the three test results shown in Figure 1, it is the first lane
in the figure that seems to be most reliable, since Tysse’s natural
EPO (which everyone produces and is thus present to a lesser or
greater extent in one’s blood and urine) is most clearly detected
in this lane (Figure 1).
The above quote from Expert Opinion implies that the second
test was initiated after the results of the first test were known.
Francesco Botré (Director of the WADA-accredited laboratory in
Ease your labwork
with HandyStep ® electronic
Lab Times
page 21
Rome and corresponding author of the article in Bioanalysis) also
stated (both orally at CAS and in a written witness statement)
that the second test was initiated because of the results they obtained in the first test. However, the laboratory’s Documentation
Package reveals that the second test was started before the results
of the first test were known.
The laboratory was, thus, either sloppy when writing their
laboratory report, or Botré’s statement is incorrect and it needs to
be clarified.
Only two credible explanations
In view of the apparent good repeatability that is reported in
the Bioanalysis article, we see only two credible explanations as
to the complete lack of reproducibility in the results obtained in
the three tests shown in Figure 1.
Either…
1. the IEF analysis method and/or the work performed in the
laboratory was so unreliable − possibly due to unspecific staining or degradation of proteins in the sample − that the entire test
must be discarded; it is then likely that the staining seen in the
CERA region is not due to CERA,
or…
2. someone in the laboratory has – on purpose or by accident
– altered or manipulated some of the concentrated urine samples,
in which case the laboratory in Rome may be accountable for serious misconduct.
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03.09.15 12:37
page 22
Lab Times
Analysis
5-2015
one such processed version that was presented at CAS as a, “falsification of a document used in a court case”. Franke also wrote,
“In conclusion, there is no scientific evidence contained in
these documents (i.e. the Documentation Package) which proves
the presence of CERA in the athlete's (i.e. Erik Tysse's) urine.” A
declaration stating the same has been signed by more than 40
professors and scientists in chemistry, biochemistry and molecular biology, including one Nobel Prize winner.
Photo: private
...and the second example
Erik Tysse is interviewed during a break at the Court of Arbitration for
Sport (CAS) trial in Lausanne by the two main Norwegian TV channels. In this trial, representatives from WADA-accredited laboratories
stated that the lack of reproducibility, regardless of cause, does not
really matter. A declaration, signed by more than 40 scientists, offers
the opposite opinion.
The documentation package that covers the Tysse case reveals several other irregularities that indicate bad laboratory procedures and may, in the worst case, suggest serious misconduct.
Some of this has already been discussed in a cover article in Lab
Times 1/2013, so in the following we will present just two additional examples.
Two additional examples of irregularity: the first...
The first example: In the laboratory's Documentation Package, one of the original gel images was inverted (i.e. presented
upside-down and right-side to left). As a consequence, the order of the sample lanes in the original image is inverted relative to the lanes in the computer-processed version of the image.
A more serious consequence of the inversion of the original image is that it made it more difficult to discover that the laboratory had, in the computer-processed version used for evaluating
the results, suppressed the staining intensity of the negative control lanes and simultaneously increased the staining intensity of
the lane that contained the athlete's sample (Source: Laboratorio Antidoping-FMSI, Documentation Package Sample B code
3511158; www.eriktysse.com/Dockuments/The%20report%20
for%20the%20B-sample.pdf).
The Rome laboratory thereby camouflaged the fact that the
negative control lanes contained the same bands as the athlete's lane (i.e. the negative control sample which did not contain
CERA was virtually identical to the athlete's sample) and that this
analysis did not present any evidence for the presence of CERA.
In a letter (dated 29th June 2011) to all participants at the
CAS hearing, Werner Franke, a highly recognised biochemist
from Heidelberg University, Germany, who played a major role
in revealing the doping culture in the former GDR, characterised
Urine samples should, according to WADA’s regulations, be
handled in such a way that the likelihood for contamination and
degradation is minimised. It is thus remarkable and bad laboratory practice that the seal on Tysse’s urine sample, which the laboratory received Sunday, 2nd May 2010, was broken and aliquoted for EPO-testing on Monday, 3rd May 2010, four days before the
test actually started (on Friday, 7th May 2010).
Furthermore, the test was started on a Friday, thus resulting
in the concentrated urine sample being left over the weekend –
two extra days – before the test was completed on the following
Tuesday (the first lane in Figure 1, page 18, is from this test).
Moreover, after having obtained the results from the second
screening test (the second lane in Figure 1 is from this test), the
laboratory waited for one week before the confirmation test was
started (the third lane in Figure 1 is from this test). And again,
Tysse’s urine was aliquoted for the EPO-test (on Monday, 17th
May 2010) three days before the test started (on Thursday, 20th
May 2010).
Just one month earlier (in April 2010), when reporting that
the Rome laboratory found the B-sample from the Italian cyclocross rider Vania Rossi negative for CERA, despite a positive Asample, Botré excused their negative B-test by saying that CERA
is unstable and degraded in urine, more so than in blood. The delayed testing after seal breakage and sample aliquoting of Tysse’s
urine sample is therefore puzzling.
Puzzling delays
Because of these delays, more than three weeks elapsed from
the time the laboratory received Tysse’s urine sample (Sunday,
2nd May 2010) until their report was mailed (Wednesday, 26th
May 2010) to the International Association of Athletics Federations (IAAF).
In contrast, when Alex Schwazer was tested positive for rEPO
in 2012 (see the "background box" on page 20 for details about
the Schwazer case) it took only seven days from the time his
urine sample was collected and analysed in the WADA-laboratory
in Cologne to reports of the positive test appearing in the press.
WADA’s regulations state that there should not be more than ten
working days from when the sample is received to a positive finding being reported, such that a blood sample can be taken in order to confirm the results obtained with urine. Blood is, especially when testing for CERA, much more sensitive and reliable. The
long delay meant that the following test of Tysse’s blood, which
was negative for CERA, could not be used as reliable evidence to
prove that he was innocent. This seriously reduced Tysse’s chances of clearing himself of the doping charges.
No will to deliver relevant information
We have contacted the laboratory in Rome as well as WADA,
IAAF, the Norwegian Athletics Association and Anti-Doping Norway and its board of directors, in order to get access to some spe-
03.09.15 12:37
Analysis
5-2015
cific information that we think might clarify whether or not Erik
Tysse used CERA and reveal the reasons for the inconsistent laboratory results. None of the above-mentioned organisations have,
however, been willing to reveal any further relevant information. Thus, we have not received information about the amount
of CERA standard protein applied to the gels, which would help
to estimate the amount of CERA that, according to WADA, is detected on the gels.
Moreover, we have not been allowed to see information that
is hidden by black rectangles at several places in the report for
Tysse’s A-sample (see images on page 20); we do not see any
reason to hide this information if the analytical work has been
performed as it should have been. We also wanted to know why
20 ml of Tysse’s A-sample urine is missing. We can only find
three possible explanations:
u the laboratory is sloppy when writing their reports,
u they have spilled some of the athlete's urine (exactly what is
required for one analysis), or
u they have carried out an additional and unreported EPO test –
the delayed testing mentioned above might indicate this.
It is unacceptable that the information we are seeking is not
freely available, since it is required to establish clearly how the
analyses were performed and should therefore be part of the laboratory report.
Lab Times
page 23
A ban on information, but why?
Finally, the recent investigations by Italian authorities that officials of athletic organisations were aware of Alex Schwazer’s
doping (see background information box on page 20), combined
with the earlier report by Alessandro Donati describing involvement of officials for sport organisations and the previous antidoping laboratory in Rome to hiding or assisting doping, makes
it even more important that all information regarding the analysis of Tysse’s sample is made available (Donati, A., Anti-doping;
the fraud behind the stage. www.playthegame.org/news/news-articles/2000/anti-doping-the-fraud-behind-the-stage).
If not, one might suspect that the irregularities we have described in this case are the result of a cover-up action, taken to
protect Schwazer, who delivered a urine sample for doping analysis in the same race as Tysse.
Jon Nissen-Meyer (University of Oslo),
Erik Boye (Oslo University Hospital & Univ. of Oslo),
Bjarne Østerud (University of Tromsø),
Tore Skotland (Oslo University Hospital & Univ. of Oslo)
Lab Times readers who have information to contribute, questions or
any other comment to make on this article should contact the corresponding author, Tore Scotland: [email protected]
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Lab Times
5-2015
Analysis
Scientific misconduct
Photo: Fotolia/michaklootwijk
French Connection
This is a story of two friends with a dubious understanding of science integrity. But even
more, it is the story of how academic and industrial research networks keep protecting them
from facing the consequences of their malpractice and misconduct.
T
he names of the two French protagonists and long-term friends are
Charles-Henri Lecellier and Guillaume Vetter. Their friendship, however,
is obviously not a relationship of equals:
despite being two years younger, Lecellier
clearly plays the dominant role – and Vetter
that of his loyal follower. At least four major institutional players have been providing the setting for their actions, namely the
2003 founded University of Luxembourg
(Uni.Lu), the French Centre national de la
recherche scientifique (CNRS), its subsidiary Institut de Génétique Moléculaire de
Montpellier (IGMM), as well as the French
biotech company Theradiag. All of them
were apparently involved in covering-up
several cases of dubious scientific practice
by Lecellier and Vetter – including deliberate falsification of data.
have, meanwhile, been found to contain
potential data manipulation; one of them
has already been retracted (Dunoyer et al.,
Plant Cell 16:1235-50).
In his only email response to Lab Times,
dated April 7th, 2015, Lecellier wrote in this
regard: “Neither am I aware nor am I implicated in the handling of that affair because
I chose to get away from Olivier Voinnet ten
years ago. I would appreciate, if you respect
my past and avoid me today to pay the double penalty." At first glance, this seemed to
be a statement by an honest scientist who
left Voinnet in protest against the poor practice of data handling in his lab. In fact, however, some first-hand reports are inclined
But let’s go back to the start. From 2004
to 2006, Charles-Henri Lecellier worked as
a postdoc in the lab of the French plant scientist Olivier Voinnet, well-known for his
research in plant immunity and the biology of small non-coding RNA. Just recently, Voinnet was found to have committed
misconduct and data misrepresentation
throughout his entire academic career by
the external investigation of his current and
past employers, ETH Zurich and CNRS (see
Lab Times online, July 12th 2015, and earlier reports).
Since the start of his postdoc time in
Voinnet’s laboratory at the CNRS Institut
de Biologie Moléculaire des Plantes (IBMP),
Lecellier has focused his work on the studies of small non-coding RNAs (precisely
miRNAs) in mammalian cell models. Several publications resulting from that time
and co-authored by Lecellier and Voinnet
LT_515_24_27.indd 24
Photo: www.mascarille.com
In Voinnet's laboratory
Good Scientific Practice seems to be a
foreign concept for Charles-Henri Lecellier
to cast a different light on the real reasons
for the break-up between Lecellier and his
mentor Voinnet.
Violent and arrogant
A former IBMP employee described
Lecellier to Lab Times as follows: “CharlesHenri was extremely violent (verbally and
physically) and arrogant. I’ve never met
anybody as violent as him in a research laboratory. He was always with Olivier Voinnet.” Furthermore, this witness added that
Lecellier was “one of the followers of Voinnet who had a totally inappropriate behaviour. It was, however, tolerated by the institute because Voinnet published in Science,
Nature and Cell. Other IBMP directors even
watched it with amusement. But it was not
fun for those people of the institute who
had to cope with all this inappropriate behaviour in the everyday life of the lab”.
As Lab Times learned from another
first-hand source, Voinnet himself admitted that he did not trust his postdoc’s experimental data and finally forced Lecellier to
leave his lab in 2006. Thus, the CNRS relocated Lecellier to its Institut de Génétique
Moléculaire de Montpellier (IGMM).
In retrospect, it seems more than ironic that Lecellier’s alleged lack of attitude
towards science integrity might have been
even too much for Voinnet, whose own publications have subsequently accrued four retractions and twelve corrections due to incorrect data presentation, so far.
Equally interesting is that, in the meantime, the publication discussion platform
PubPeer has been providing evidence for
even earlier forays of Lecellier into “creative” data presentation, namely from his
time as a PhD student in the virology lab
of Ali Saïb at the CNRS Hôpital Saint-Louis in Paris. Saïb himself stated on the sus-
03/09/2015 13:44
Analysis
picions against his former lauded PhD student (Mention très honorable avec les félicitations du jury): “During his PhD, nothing
could suggest any misconduct.” Yet, Lecellier’s two first-author publications on foamy
viruses show strong evidence for manipulative re-use of blot images, in utterly different contexts and across the separate publications (J Virol, 76(7):3388-94 and 76(14):
7220-7). Accordingly, the journal’s editorin-chief, Rozanne Sandri-Goldin, promised
in an email to Lab Times: “Given the public
and sensitive nature of this case, we will
follow our well-established process to investigate the allegations as they appear on
PubPeer.”
Lecellier’s conflict with Voinnet at the
IBMP in Strasbourg ultimately emerged in
2006 over his first research project as an independent scientist and his first collaboration with Vetter (who was also previously
employed at the IBMP, in the laboratory of
David Gilmer). The majority of the data for
the project was produced by Vetter, who,
in the meantime, had moved to Luxembourg for a postdoc at the C
RP-Santé (now
named Luxembourg Institute of Health),
where he mainly operated a DNA micro
array platform managed by the Uni.Lu pro-
5-2015
fessor Evelyne Friederich. Despite Lecellier’s conflict with Voinnet and rejections by
two journals, the resulting paper was eventually published in Blood, with Lecellier’s
wife Anna Saumet being first and Vetter
second author (113(2):412-21).
The Blood paper described the role of
various miRNAs on the expression of cancer-relevant genes in leukaemic cells carrying the common oncogenic mutation
PML-RAR. Potentially, this study could have
been very important for clinical applications and patient therapies. If it were reliable, that is. On PubPeer, once again a duplicated miRNA blot was flagged for that publication, while purportedly showing completely different miRNAs under different experimental conditions.
Spot the difference!
Yet, this is not all. Lab Times has obtained the original manuscript version from
March 2008, which Lecellier initially submitted to Blood. We compared it with the
revised manuscript, which Lecellier resubmitted after peer review and which was finally published by the journal. The exercise was similar to the popular children’s
game of spotting the differences between
Lab Times
page 25
two similar images – and in the figure below the reader is invited to do the same. To
conclude, it quickly became clear that certain values inside several gene expression
analyses had been selectively altered, while
other values of the same experiment as well
as their error bars had remained exactly the
same. Apparently, neither the editors nor
the peer reviewers had noticed any of those
oddities, which are, at the very least, unacceptable in terms of a properly controlled
experiment. To our inquiries, Blood journal’s senior manager for peer review, Virginia Ramsey, only replied that the data
“have been forwarded to our Data Integrity Manager and are being processed accordingly”.
After that successful publication, Lecellier and Vetter moved on to a new project, which Vetter again largely performed
in the Uni.Lu lab of the cell biologist and
cytoskeleton specialist, Friederich. The outcome was an Oncogene paper, in which Vetter, Lecellier and Co. postulated an active
role for a certain miRNA (miR-661) in the
promotion of tumour cell invasiveness in
breast cancer, by inducing the epithelial to
mesenchymal transition. According to the
authors, they had identified the epitheli-
The panel in figure 7D, showing a luciferase assay for the miRNA effect on reporter gene expression, was modified upon resubmission. It was
extended by two new experimental conditions (marked red), with a key positive control (“mixed LNAs”) significantly changed. (The latter modification made the impact of certain anti-miRNA treatments appear significantly greater). All other values (including their error bars) remained
exactly as before. This practice by Lecellier and Vetter suggests, to the least, an inappropriate patchwork of intra-variable experiments, which
prohibits any reliable comparison of values. Nevertheless, Lecellier insisted in his revision letter that the added values can be directly compared to the previous ones, despite the profound intra-experimental variability. He only forgot to mention the introduced sudden, dramatic
change in the positive control (“mixed LNAs”)!
LT_515_24_27.indd 25
03/09/2015 13:44
Lab Times
al genes Nectin-1 and StarD1 as key targets
for miR-661.
Soon after publication, however, senior
author Evelyne Friederich and her co-workers themselves discovered irregularities in
some of the data presented in the paper,
and initiated an investigation into possible
misconduct at the Uni.Lu. In the end, an external commission found that the entire experimental data on Nectin-1 had been manipulated by Vetter. Thus, retraction of the
paper was the logical next step.
Correction instead of retraction
Curiously, exactly this move was strongly opposed – not only by the CNRS, Lecellier’s employer, but also by parts of the U
ni.
Lu. A deal was therefore made to pursue
the commission’s alternative recommendation: to correct the paper, despite its proven fraudulent data. Yet, even for this route
no agreement could be achieved among the
parties involved, mainly because Lecellier
continuously insisted that there had actually never been any misconduct but that, instead, pure “personal conflicts” had led to
the accusations against his innocent friend
Vetter. Also, the IGMM group leader and
co-author, Charles Theillet, fully concurred
and wrote to Friederich: “None of the elements you came up with support overt and
deliberate manipulation of data.”
On June 10th, 2015, Lab Times first reported online on the details of the dispute
surrounding the Oncogene publication by
Vetter et al. (29, 4436-48) and the misconduct investigation by the Uni.Lu. The entire affair can actually be summarised as
follows: In the end, almost anyone wanted to protect Vetter from the consequences
of Friederich's accusations, despite all the
clear evidence and even despite the incriminating results of the formal institutional investigation. But why?
The University of Luxembourg is rather
young (founded 2003) but it has already
been shaken by some cases of data manipulation. The first case, which resulted in Uni.
Lu’s first external misconduct investigation,
was that of the German bioinformatician
Carsten Carlberg. After intervention by the
Luxembourg funding agency, Fonds National de la Recherche (FNR), Carlberg was finally sacked from his professorship position at Uni.Lu for being involved in scientific misconduct, which had led to the retraction of two of his publications (see LT
4-2011:12). Following this experience, an
Ethics Review Panel was established at Uni.
Lu. It wasn’t too long before it was needed.
An assistant professor at the Life Science
LT_515_24_27.indd 26
Analysis
5-2015
Research Unit (LSRU), Eleonora Morga,
was found to have manipulated data in a
neurobiological study, which was later retracted by the journal Glia (62(3):491).
The paper’s last author was Morga’s former PhD advisor Paul Heuschling, Dean of
the Science Faculty at Uni.Lu. Apparently, Heuschling, with the help of the thenChancellor of Uni.Lu, Eric Tschirhart (now
vice-president for academic affairs), tried
their best to prevent an external investigation and to avoid the retraction. All this,
despite the clear evidence presented by
Morga’s own lab members that she had, in
fact, manipulated data (in the Glia publication and elsewhere) and despite the fact
that Morga failed to provide her co-authors
with the corresponding primary data. Eventually, Morga was sacked.
Money-back policy
tionship. As soon as Friederich began to
question Vetter’s scientific data, Tschirhart
quickly moved him to his own team, away
from her oversight and control. Just when
Vetter was supposed to be questioned by
the investigative commission, he slipped
away to his friend Lecellier in Montpellier
– with the help of a vacation permit issued
by Tschirhart. It would not be fair to claim
that Tschirhart did not take Friederich’s
misconduct accusations against Vetter and
Morga seriously. Indeed, he very much did.
When Friederich invited senior scientists
to the “extraordinary LSRU (Life Sciences
Research Unit) meeting” on October 24th
2011, to discuss the accusations against
Morga and Vetter, Tschirhart immediately
reminded her that by initiating this meeting, she might have breached the Règlement d’Ordre Intérieur (ROI, internal code
of conduct) – which could, in turn, result
in her own dismissal (Vetter and Morga
were co-recipients of Tschirhart’s email).
Furthermore, during the actual meeting,
Tschirhart openly accused Friederich of being in breach of confidentiality as well as
acting outside of her authority.
One of the reasons for the initial resistance against taking the appropriate measures, in this case, might have been money:
the FNR has a policy of demanding back
their research funding, if it has been invested in a publication that later has to be retracted due to misconduct.
Putting blame on others
Concerning Vetter’s Oncogene paper, the
Soon after his arrival at Lecellier’s lab
officials from Uni.Lu obviously also feared
in Montpellier, Vetter had the audacity to
that the FNR would claim its money back
blame Friederich and her co-workers for his
in the eventuality it might be retracted. In
own misconduct. He justified his data maa letter from October 9th, 2013, Heuschling
and the vice-president for research, Ludnipulations with allegedly having been “a
wig Neyses, informed Friederich that the
mobbing victim” and suffering under “morFNR “is willing to reconsider its decision
al pressure” in the lab. Rumours spread that
of having the University reimburse the enVetter was even thinking about taking legal
tire budget of your
actions against Uni.
FNR project, if we
Lu. The Friederich
can prove that the
team, therefore, asjournal Oncogene is
sembled a protest
indeed willing to acnote to the Uni.Lu’s
cept, pending apEthics Review Panproval, a corrected
el, which remained
version of your pubunanswered.
lication instead of
This way, V
etter
a complete retracremained largetion”. And they furly unscathed for
ther stated that “the
the time being but
University must
the Oncogene paseize this opportuper was doomed.
nity”. Thus, not only
In October 2014,
the CNRS was keen Blames others for his own misconduct:
Heuschling, Neyto avoid a retraction Guillaume Vetter
ses and Behrmann,
of Vetter’s work as a
together with the
consequence of the misconduct confirmathen Uni.Lu president Rolf Tarrach, cotion by the formal investigation but also the
signed an official request to the journal to
Luxembourg science directorate, including
retract the paper. Nothing happened, probthe head of LSRU, Iris Behrmann.
ably because the CNRS as well as Tschirhart
Money, however, was only one aspect.
and even the Ethics Review Panel at Uni.Lu
Another was some obscure personal relastill disagreed with a retraction. A couple
Photo: Friederich lab
page 26
03/09/2015 13:44
Analysis
United again at biotech company
Four years ago, Lecellier together with
IGMM founded the biotech company Prestizia, for the purpose of miRNA diagnostics
and personalised medicine. Prestizia was
later acquired by the diagnostics company Theradiag, which then went on to win
the Worldwide Innovation Challenge from
the President of France for its activities into
miRNA applications. As IGMM proudly announces on its website, their staff scientist
Lecellier has since been supervising the collaboration with Theradiag on the HIV diagnostics research. And, perhaps unsurprisingly at this point, Vetter was installed
as Head of miRNA Laboratory at PrestiziaTheradiag, directly after he had had to flee
from Luxembourg, in order to avoid facing
the responsibility for his misconduct.
When contacted by email, Theradiag declined to comment on Vetter’s employment
but wished to know the names of those
people, who had provided Lab Times with
this information. Given all this, is it too farfetched to speculate that the CNRS might
still be pinning some high hopes on Lecellier and Vetter, in the light of their particular involvement with the biotech industry?
Also, in 2012 IGMM and Lecellier
teamed up with the US company Thomson
Reuters, to apply their bioinformatics analysis platform, MetaCore, to the prediction of
candidate miRNAs and their interactive networks with transcription factors and gene
expression. Lecellier’s previous experience
with a similar but academically-generated
LT_515_24_27.indd 27
Lab Times
page 27
bioinformatical database, however, is very
revealing indeed. In fact, shortly after the
accusation of misconduct at the Uni.Lu,
Lecellier and Vetter, in their next publication, boldly misappropriated and misrepresented bioinformatics data and mathematical calculations from the Friederich lab.
For this paper, Lecellier and Vetter applied the unvalidated bioinformatics approach from MIR@NT@N, mixed with additional calculations from MetaCore, to retrospectively predict their cell biological results. Le Béchec was named, despite his protest, in the Acknowledgements and, in this
way, was assigned the responsibility for the
The convenient way
statistically poor calculations in Figure S2 of
These were originally generated by
the publication. Those were even deemed
the bioinformatician, Antony Le Béchec,
by the journal’s editorial board as incorwho was explicitly
rect, namely found
funded to establish a
to have been based
web interface methon the wrong primod that would preers. Le Béchec: “I did
dict high-confidence
not validate the [bio
miRNA targets and
informatics] data degene-mRNA-miRNA
scribed in this publiinteraction networks
cation, neither the
involved in the eppreliminary methithelial to mesenod used to generate
chymal transition.
these data [in FigBack then, Lecelliure S2]. I informed
er proposed testing Evelyne Friederich wants to bring the data
Lecellier that he
Le
Béchec’s predic- manipulations to light but is accused of actcould not use and
tion software, named ing outside of her authority.
publish these prelimMIR@NT@N, experinary data because
imentally in his own lab, by focusing on
of the poor statistical relevance of the remiRNAs and transcription factors in breast
sults and the not yet, and probably never,
cancer cells. According to Le Béchec, howvalidated method used.”
ever, the determined Montpellier researchMissing letter
er apparently chose a more convenient apAs soon as Friederich became aware of
proach of retrospectively fitting the predicthis Molecular BioSystems publication, she
tions of the immature bioinformatics pipeand Neyses expressed their “concerns reline to match his own wet-lab data. It went
garding data ownership, co-authorship and
so far that Lecellier even insisted on using
funding” on behalf of Uni.Lu to the journal’s
statistically non-validated calculations (sochief editor (letter available to Lab Times).
called “candidate approaches”), as long as
Later on, when the publisher, the Royal Sothey looked supportive of his theories. And
ciety of Chemistry, started its investigation
finally, he even arranged co-authorships in
into the case, this letter from June 3rd 2013
his proposed publication manuscript for
could not be found, neither by Molecular
Vetter and his wife Anna Saumet, so that
BioSystems nor by the Uni.Lu. Nevertheless,
they would actually share the first-author
the Royal Society’s Publishing Ethics Spemerits with Le Béchec.
cialist, Emily Skinner, assured Lab Times:
Friederich and Le Béchec, as well as an“I am currently reviewing the matter in corother senior co-author, the bioinformatics
respondence with the University of Luxemgeneticist Wyeth Wassermann from the
bourg”.
Centre for Molecular Medicine and TherOf all these problematic Lecellier/Vetapeutics in Vancouver, Canada, protestter papers, not one has been corrected or
ed against such use of unvalidated and inretracted, so far. The CNRS remains siconclusive data. In the end, they decided
lent. And the Uni.Lu now has another case
to cease the collaboration with Lecellier, in
of misconduct to deal with: the German
order to further validate their MIR@NT@N
neuroscientist Jens Schwamborn. Shortly
software. This work was later published,
after he was recruited as professor at Uni.
without Lecellier and Co., in BMC BioinforLu, Schwamborn was found to have commatics (12:67).
mitted misconduct and data manipulation
Lecellier, on the other hand, pubin two, meanwhile retracted, publications
lished his own wet-lab results from the
from his time as PhD student at the UniverIGMM separately in Molecular BioSystems
sity of Münster.
(8(12):3242-53), with Anna Saumet and
Leonid Schneider
Vetter as first and second author.
Photo: Friederich lab
of days after the first Lab Times report had
gone online on June 10th, Nature Publishing Group finally announced the retraction
would appear by June 29th. But, as it transpired, they weren't able to make it happen. Instead, the back-and-forth negotiations about the precise wording of the retraction notice and, in particular, about the
question of whether or not to mention that
the formal investigation found Vetter exclusively responsible for the data manipulation, was still continuing when this issue
went to press.
In contrast to the Uni.Lu, the CNRS always stood united – albeit on the side of
Lecellier and Vetter. Unfortunately, all Lab
Times email inquiries in this case went completely unanswered by the French side, a
situation we had already become rather familiar with during our investigations into
the Olivier Voinnet case. Nevertheless,
there are at least some possible indicators
for CNRS’ somewhat unfathomable “overprotective” behaviour.
5-2015
03/09/2015 13:44
What does ‘excellence’ really mean?
‘Excellence’
or Non-Sense
Photo
(2):
Foto
lia/C
laud
ia Pa
F
or years, we seem to have been bombarded with claims that everything
must be done in the name of ‘excellence’. Only research that is excellent can
be funded, only universities that are excellent will continue to do research, only researchers who are excellent can hope to get
a job. And of course, all of the administration and management who decide upon the
criteria for ‘excellence’ must, by association,
be somehow excellent in their good taste
and judgement. But what, when you come
down to it, does this magical quality called
‘excellence’ actually mean? Given the importance of these decisions, it may surprise
some that the definitions of excellence are
not so clear-cut (see text box on pg. 30).
Traditional excellence
The traditional view of universities has
been based on trust. It assumes that academics in universities are ‘excellent’ at doing what they do, that is, that they are ‘fit’
for the purpose of teaching and research. It
believes that professors and scientists are
mainly engaged in research because they
are interested in understanding the world
they live in, and because they are motivated to come up with new explanations
and solutions. “Academic work was not assessed systematically, since it was tacitly assumed that academics would strive for excellence without having to be forced to do
so.” The government merely determined
the amount of money that was paid to universities and set the legal framework for science and teaching. In terms of research, the
government did not impose specific policies. And this was generally the situation
until around the 1980s.
But the Swiss economist Mathias
Binswanger admits this was not a perfect
LT_515_28_31.indd 28
uluss
en
‘Excellence’ is currently a word used to justify many funding decisions in research and higher education but what do
we actually mean by excellence? Jeremy Garwood looks at
how traditional notions of academic excellence have been
transformed by the application of ‘free market’ dogmas.
system – there were huge differences in
quality between individual scientists. “Scientific geniuses and lame ducks jointly populated universities, whereby even during
the scientists’ lifetimes it was not always
discernible who was the lame duck and
who the genius.” Nevertheless, he argues
that the system that has replaced it is far
worse (How Nonsense Became Excellence:
Forcing Professors to Publish in ‘Incentives
and Performance. Governance of Research
Organizations’ 2015, springer.com).
Now, instead of making funds directly
available to universities, governments insist
that their research and teaching should be
evaluated first. Universities are then ranked
relative to one another in league tables.
More funds are provided to higher-ranked
institutions – only the best get a chance to
do more research.
Binswanger says this resulting competition for funds has made universities forget about their ‘noble purpose’ of increasing knowledge. Instead, they have “degenerated into ranking-minded fundraisers
and publication factories”. Furthermore,
he says, this degeneration is firmly rooted
in the now-fashionable and omnipresent
‘search for excellence’, in which universities are supposed to outperform each other and everybody tries to appear more ‘excellent’ than everybody else. This is what
Binswanger terms the ‘contest illusion’.
In these artificially-staged competitions,
the major challenge for universities has now
become how to get additional funding by
creating a good impression with the relevant research commissions. Demonstrating
measurable excellence increases the probability of getting more funds. The problem is
that no-one really knows what excellence is
“least of all the politicians who launch such
excellence initiatives”. It is simply assumed
that these competitions will automatically
enable the best to rise to the top, without
any need to care about either the content
nor the purpose of the excellent research.
The rise of New Public Management
During the 1980s, the ‘contest illusion’
was first applied to science in the UK, where
it was part of an entirely new approach to
the organisation and operation of public
services called New Public Management.
This was not confined to universities and
academics.
In his essay, “If You’re So Smart, Why
Are You under Surveillance? Universities,
Neoliberalism, and New Public Management” (Critical Inquiry, 2012), Dutch philosopher Chris Lorenz describes how New
Public Management began in the USA but
found its most fertile ground in the UK under Margaret Thatcher’s government. It has
subsequently spread worldwide.
As Lorenz explains, New Public Management (NPM) is the neoliberal dream of
the free market economy and ‘Homo economicus’ applied to the public sector. At its
heart is a free market conception of how
everything can be done more efficiently by
following its central dogma: free market =
competition = best value for money = optimum efficiency for individuals as both
consumers and owners of private property.
NPM redefines the public sector as a service sector that functions best when it operates in accordance with the principles of
the free market.
In the UK, the arrival of NPM was
marked by the introduction of private sector
management techniques and management
strategies. For universities, the Thatcher
government developed league tables that
03/09/2015 14:16
Analysis
relied on quantifiable indicators and were
claimed to rank institutions by the quality
of their teaching and research.
Evaluating ‘excellent’ research
The Research Assessment Exercise
(RAE) was introduced in 1986 to rate UK
research “in order to facilitate allocation
of funds and to strengthen the international competitiveness of the UK academic research base”. It was essentially a peer review process, based on assessments made
by panels appointed to examine research
in UK universities. The process was repeated in 1989, 1992, 1996, 2001 and 2008. It
was then ‘rebranded’ as the ‘Research Excellence Framework’ (REF).
The first REF took place in 2014. For
this, UK universities had to submit four ‘research outputs’, usually peer-reviewed articles, for each participating academic faculty member. In total, 154 UK universities
submitted 191,150 research outputs from
52,061 academics. Each of these outputs
was evaluated by a panel of peer-reviewers, who provided it with a score of 4-star
(quality that is “world-leading in terms of
originality, significance and rigour”), 3-star
(quality that is “internationally excellent”),
2-star (quality “recognised internationally”)
or 1-star (“recognised nationally”).
These REF ratings are very important in
UK academic circles – they determine the
distribution of £1.6 billion per year. While
REF results have no implications for a given
individual, they have “huge implications for
the relative standing of fields, the research
funding of universities, and funding allocated within universities to different research
groups” (PLoS ONE, 10(7):e0132990).
Yet throughout all these evaluations,
no-one knows for certain what is meant by
‘excellence’. For example, when introducing
the RAE in 2000, Scotland’s Higher Education Funding Council helpfully explained
that “excellence is generally taken to mean
outstanding, or of a quality that surpasses
a defined threshold in a particular field”.
However, “in the case of research, there is
no agreed way in which excellence is defined or measured uniformly across different disciplines at the international level,
although some attempts have been made
using bibliometric analyses, with limited
success”. Therefore, the UK Higher Education Funding Councils (including Scotland)
“currently seek to measure the quality of research at the national level in all subject areas through periodic Research Assessment
Exercises. The RAE does this by assessing
research against assumed measures of in-
LT_515_28_31.indd 29
5-2015
ternational excellence. It does not however seek to benchmark quality against international comparators since there are no internationally agreed measures of quality”.
Matters were not much clearer for the
REF 2014. Overall, research submissions
were assessed by an ‘expert sub-panel’ for
each one of the 36 subject areas (‘units of
assessment’). In total, there were 36 subpanel chairs, 1,052 members and assessors, and 25 specialist advisers. These subpanels worked under the guidance of four
main panels (consisting of four main panel chairs, 23 international members and 17
user members). It was the responsibility of
the main panels to ensure the assessment
criteria and standards were consistently applied. The international members were expected to provide assurance about the international benchmarking of standards.
Yet, nowhere is it clear how these ‘standards’ are to be measured. Instead, the panels were expected to ‘calibrate’ their own
quality standards:
“Each main panel and its sub-panels
will undertake calibration exercises at an
early stage in the assessment to develop a
common understanding of the assessment
standards and the application of the quality levels. International and user members of
the main panel will participate in these exercises to assist in benchmarking judgements.
The main panel chair and members of the
main panel will attend a selection of the subpanel meetings that deal with calibration exercises and main panels will receive and discuss reports from sub-panel chairs on these
exercises.” (paragraph 107e from the REF’s
‘Panel criteria and working methods’).
However, the ‘quality’ of the resulting
evaluations has been heavily criticised.
For example, between 2008 and 2014, the
REF 2014 reported an astonishing 103% increase in ‘world leading’ 4-star research outputs in UK life science and medicine (Times
Higher Education, 27/07/15).
Meanwhile, such evaluation exercises
cost a lot of time and money. It was recently estimated that, in total, UK universities
spend £1 billion meeting such demands for
‘quality assurance’ (Times Higher Education,
30/06/15).
Spreading excellence
Other countries have followed the UK’s
lead and introduced their own national frameworks for evaluating the research
output of universities as a basis for funding decisions. The European Commission’s
2010 report on ‘Assessing Europe’s University-Based Research’ identified 14 countries
Lab Times
page 29
– Australia, Belgium, Denmark, Finland,
France, Germany, Italy, the Netherlands,
New Zealand, Norway, Portugal, Spain,
Sweden and the UK. Most of these systems
emphasise an assessment of the ‘excellence’
of research, using peer review and/or bibliometric approaches. Germany began its
‘Exzellenzinitiative’ in 2005, allocating 4.4
billion euros between 2006 and 2015. Spain
launched its Campus of International Excellence competition in 2009 that gave its ‘excellent’ universities the chance to carve up
200 million euros. Meanwhile, France has
become ‘excellent’ at finding new names
for its schemes. In 2008, it launched ‘Operation Campus’, a competition aimed at
creating ‘campuses of excellence’. This
was followed by competitive projects with
names like ‘Equipex’ (Equipment of Excellence), ‘Labex’ (Laboratories of Excellence)
and ‘Idex’ (Excellence Initiatives). But it is
never clear what is actually meant by ‘excellence’.
European research excellence?
The definitions are no clearer at the European level. The European Research Council (ERC) awards large five-year grants in
three categories – Starting grants (up to 2
million euros), Consolidator grants (up to
2.75 million euros) and Advanced grants
(up to 3.5 million euros). There is considerable competition for these grants. Under the
EU’s Horizon 2020 programme (from 20142020), the ERC plans to distribute around
7,000 of them.
The ERC states that the “sole evaluation criterion” for their grants is the “scientific excellence” of researchers and research proposals. Under ‘Evaluation Panels’
this is reiterated: “The selection of scientific and scholarly proposals for ERC funding
is based on international peer review with
‘excellence’ as the sole criterion.” But the
ERC does not provide a definition of ‘excellence’. Instead, you are told to look elsewhere: “The evaluation criteria are established in the Horizon 2020 Rules for Participation.”
However, the ‘Horizon 2020 Rules for
Participation’ (at ec.europa.eu) only discuss ‘excellence’ in “Article 15: Selection
and award criteria.
1. The proposals submitted shall be
evaluated on the basis of the following
award criteria: (a) excellence; (b) impact;
(c) quality and efficiency of the implementation.
2. Only the criterion referred to in point
(a) of paragraph 1 shall apply to proposals
for ERC frontier research actions.”
03/09/2015 14:16
page 30
Lab Times
Analysis
5-2015
In fact, nowhere is there an explanation
of how the ERC actually measures the elusive quality of ‘excellence’ when distributing its funds!
says, we should be giving more chances to
young researchers who are currently ‘good’
because we do not know how they will develop and cannot identify, who among them
will come to be recognised as tomorrow’s
excellent scientists.
Given the limited funds available to
funding agencies, he suggests it would be
better to give more small grants to many
researchers (say 50%) rather than to give
a few large grants to small numbers of elite
researchers (<5%). Especially since large
grants would only be more effective if it
could be shown that scientific impact increases as a growing function of grant size.
But instead, quantitative studies of this
funding problem indicate that strategies
the pursuit of excellence is only the mirage
reflection of an ideological and unrealistic dogma.”
(Not) Seeing Excellence
Lars Walløe, President of Academia
Some arguments against excellence
Europaea, discussed the problems of recMany critics oppose the use of ‘excelognising excellence in a 2009 talk on ‘The
lence’ as a buzzword to justify all kinds of
meaning of excellence and the need for exdecisions about the funding of researchers
cellence in research’ (transcript at: ae-info.
and projects, the reorganisation of univerorg). Walløe, a physiology professor in Norsities and research centres, the waste of reway, has been on many funding commitsearch resources, and a demoralising sense
tees and chaired a panel deciding on ERC’s
that science is getting lost.
Starting Grants. He said they constantly
The ‘Dogma’ of Excellence
faced the problem of deciding which proFrancesco Sylos Labini, co-founder of
posals seem to be the most promising. He
Italy’s research forum ‘Return on Academagrees that we can’t really predict excelic ReSearch’ (ROARS), condemns what he
lence in the future and goes further, by saycalls the ‘dogma of excellence’.
ing that even assessments of
This pretends to assign the largpast excellence have often
est part of available research
been shown to be matters of
funds only to the best scientists
subjective understandings
(Euroscientist, 29/01/14). But
of the relative importance
Labini questions whether we
of certain lines of study and
What is excellence? - In the case of research, there is no agreecan really assess who will be exdiscovery, and the personal
ment regarding the definition of excellence and its measurement
cellent in the future and if this is
claims for credit in this reacross different disciplines at the international level.
the best way of supporting new
search.
Is excellence absolute or relative? - Excellence is a highly relaand productive research.
Hence, in the present –
tive concept. It implies a judgment that evaluates if and to what extent
Currently, researchers are
now
– how do you judge exsomething or someone possesses some definite intrinsic characterisforced to compete with each
cellence? It’s a problem.
tics to be considered excellent (in relation to oneself and others)
other for the allocation of reYou have bibliometrics
An alternative definition of ‘Excellence’: an intangible noun desources, yet only a small fracwhich are popular because
rived in recent decades from an adjective meaning anything that is not
tion will be able to obtain the
they are pseudo-objective
directly in opposition to a mission statement. Basically it is supposed
funds needed to fully develop
but Walløe says you can’t
to mean ‘good-ness’, but better than good, really good. But without
their own research projects. This
tell much from impact facany increase in quality of work to back it up. So it can be anything
has two negative consequences.
tors and citations. Moreover,
from poor to mediocre to decent to great to outstanding. In all conFirst, although some competihe asserts that many citation
crete reality, excellence means nothing but you’ll see it everywhere to
tion is good for public research,
chasers are not so good at redescribe everything.
it is clear that there is a threshsearch. “I often meet scienExcellence as “bullshit”: Modern management of universities
old, beyond which competition
tists who see obtaining high
creates more adverse than posbibliometric factors as the
and scientific research has produced its own “official bullshit.” Three
itive effects. He argues that an
prime goal of their work.
types of statements play a key role:
excess of competition stimulates
Too many of them are not re“Excellence-speak” (or “Top-speak”): statements that identify
misbehaviour (for example,
ally excellent but have been
the underfunded public universities (of the US, the Netherlands, Gerfraud and stealing of credit in
lucky or work in a field where
many, France, etc.) with the top private universities in the US;
scientific publications) and an
it is easier to obtain many ci“Valorization-speak”: statements that identify the academic
invasive pressure on the choice
tations.”
worth of research with economic market value;
of research topics made by indiSo, then we have ‘peer re“Quali-speak”: statements that identify the quality of education
viduals. Second, faced with the
view’. But again, Walløe says
with quantitative educational output.
risks of excessive competition,
people fail to realise just how
young scientists are becoming
subjective and narrow these
Sources: ‘The concept of excellence in higher education’ a report by the European
increasingly conservative in
judgements can be. It only
Association for Quality Assurance in Higher Education, 2014; www.urbandictionary.
their approach to research, infunctions well if the chosen
com; C. Lorenz “If You’re So Smart, Why Are You under Surveillance? Universities,
vesting research time in mainpeers are not only good sciNeoliberalism, and New Public Management”, Critical Inquiry, 2012.
stream ideas that conform to
entists themselves but also
peer pressure and job market rehave a broad-minded apquirements rather than explorproach to what constitutes
ing innovative ideas.
excellent scientific contributions in their
targeting research diversity, rather than
The basic problem is that today’s deciown field. “Too many scientists who are
‘excellence’, are more likely to be producsions to finance researchers are based on
excellent researchers consider somewhat
tive in the long-term.
who and what is judged to be excellent at
naively that the only right way to do sci“The evaluation of scientists needs to
this particular timepoint. Instead, Labini
ence is exactly the way they themselves do
give space to different degrees of quality:
The Definition of Excellence
LT_515_28_31.indd 30
03/09/2015 14:16
Analysis
it.” And often these scientists become referees, advisors or even the decision makers at
various levels. “This attitude to excellence
can have serious consequences, since really
promising scientists or projects may get lost
in the selection process.” Walløe said he often found it necessary to remind a committee of peers of the truism that excellent contributions to science can be made in very
different ways and at very different levels
in the research process.
Good better than excellent
Furthermore, Walløe questions the obsession with excellence – “Is excellence
in research always needed? I believe not.
Sometimes we need good reliable science
but not necessarily excellent science, because there is a piece of standard research
work which has to be done and done reliably. A new treatment may, for example,
need to be compared to an old method to
determine, which is better, or a new piece
of equipment needs to be developed.
“There are many ways to do good science and even excellent science. One researcher may formulate a new hypothesis
based on the failure of an older one. This
may be an important contribution, even if
the scientist involved is not able to test the
hypothesis herself. Other scientists may
develop important new methods or equipment, or painstakingly collect data in a
laboratory or in the field using established
methods. Similarly, just collecting the necessary data or doing the right experiments
to test a new hypothesis formulated by
someone else could also constitute excellent and valuable science. Critical reanalysis of other people’s published or unpublished works, with full acknowledgement of
the original author, can result in important
new insight and thus represent excellent
work in science. There are many different
scientific activities which can be excellent
if they are done in the right way.”
Antisocial Excellence
Jack Stilgoe wrote an article ‘Against
Excellence’ (The Guardian, 19/12/14). He
claims the traditional definitions of excellence applied to scientific research are at
odds with new perceptions of what science
ought to be about. It is not enough to say
that the research is being performed to the
highest standards of integrity and reason,
it must also have a sense of social ‘responsibility’.
“Is science just about letting researchers pursue their own favourite explorations
through their chosen topics? Are we really saying that researchers who have been
LT_515_28_31.indd 31
5-2015
Lab Times
page 31
given the ‘excellence’ label/brand are completely free to do what they like with the
public funds entrusted to them?” Stilgoe,
who teaches science policy at UCL London,
helped draft the ‘Rome Declaration on Responsible Research and Innovation in Europe’.
He argues that making excellence the
main justification for funding science tells
us nothing about how important the science
is and everything about who decides. “Excellence is judged by peers and backed up
by numbers such as h-indexes and journal
impact factors, all of which reinforces disciplinary boundaries and focuses scientists’
attention inwards rather than on the problems of the outside world.” Prioritising excellent research perpetuates the reproduction of scientific elites and the concentration of scientific research in particular disciplines and places.
Although he agrees we need ERC and
other ‘blue-skies’ funding as part of the innovation ecosystem, the danger is that, by
identifying this as ‘excellence’, it “damns”
everything else to mediocrity, including applied science, user-driven innovation, open
science, meta-analysis, regulatory science,
social innovation, and engagement with
policymakers and the public. In the last
thirty years, our sense of excellence has
narrowed, not broadened. Against the assumption that quality is one-dimensional,
it becomes harder to make the case for diversity in science.
important both for individual scientists and
for universities. As a result, they have become “publication factories, bound to maximize their publication output”.
The ideal professor in these modern
universities is a mixture of fundraiser, project manager and mass publisher (mostly
as a co-author of publications written by
his or her assistants since “he or she has no
more time to do research”), whose main
concern is a measurable contribution to scientific excellence rather than increasing our
knowledge.
In order to make sure that professors
will deliver their contribution to excellence,
faculty managers have been recruited for
each department in addition to traditional
deans. “They act like CEOs in private companies and they are supposed to implement
new strategies for becoming increasingly
excellent.” Research becomes a means in
the battle for ‘market shares’ of universities
and research institutions. Winners are rewarded with elite or excellence status “notwithstanding the fact that many projects
and publications do not have the slightest
importance for people outside and often
even inside the academic system”. Nevertheless, notes Binswanger, these measurable outputs play a central role in today’s research rankings; for example, in the ‘CHE
Research Ranking of German universities’
where they are advertised under labels,
such as ‘more excellence’ and ‘more efficiency’.
Stop using the word
Motivation fosters excellence
Responsible research and innovation
(RRI) in the service of grand challenges
also means transforming the way we fund
science. In many ways, this means revisiting models used in the past but forgotten with the rise of excellence. Stilgoe concludes that “if we cannot find a way to expand our sense of what counts as scientific
excellence, let’s stop using the word”.
Excellence as Nonsense
Mathias Binswanger analyses ‘how nonsense became excellence’ in universities and
scientific research. He argues that modern
universities are no longer focused on gaining knowledge. Instead, they have become
exclusively committed to measurable excellence and “the search for truth often does
not help much in this respect”.
Universities are now “fundraising institutions determined to receive as much money as possible from government researchfunding programs or private institutions”.
This entails a competition for rankings
based on publications and citations that are
Another serious consequence of the permanent competition for publication is the
demotivating effect on scientists. “More and
more people employed in the research system spend more and more time on things
that have nothing to do with true research.”
Their intrinsic motivation for pursuing scientific knowledge is being increasingly
‘crowded out’. For Binswanger, a scientist
who is not truly interested in his work will
never be a great scientist. Yet exactly those
scientists, who are intrinsically motivated,
are the ones whose motivation is usually
crowded out the most rapidly. “They are often rather unconventional people who do
not perform well in standardised competitions, and they do not feel like constantly
being forced to publish just to attain high
scores.” And if intrinsic motivation is lost,
so will a lot of potentially valuable research,
because intrinsic motivation is a necessary
condition for ‘true excellence’.
Jeremy Garwood
03/09/2015 14:16
Lab Times
Journal Club
5-2015
Brain evolution in Helsinki, Finland
Fishing for Evidence
Which factors drive brain evolution in threespine sticklebacks? Juha Merilä and colleagues in Finland and Hungary
answered this question with a trip to the seaside at Helsinki, where they caught wild fish with a seine net.
T
hreespine sticklebacks (Gasterosteus
aculeatus) are of particular interest
to both ecologists and evolutionary biologists. That’s because the 5 cm fish
evolved into many divergent, locally adapted populations after the last ice age; they
are also easy to breed and keep in aquaria, feeding mainly on chironomid larvae;
they have a short generation time and last
but not least, their genomic make-up has
been known since 2006. Their name-giving
spines, together with bony lateral plates,
are their defence against predators and
make the fish difficult to swallow. In the
wild, threespine sticklebacks live in fresh
water, estuaries and coastal seas throughout the Northern hemisphere. During the
winter, they are pelagic and can be found
over 500 km offshore.
Sex-life on tv
breeders. They crossed wild fish in vitro by
mixing surgically-gained sperm with eggs.
Finally, 231 sticklebacks had their brains
dissected, fixed in formalin, photographed
and measured. “Technically, after the delicate work of dissecting and of measuring the size of brain regions, the biggest
challenge was informatics. We waited and
hoped that the computer did not crash
while running models, which we used to get
estimates of heritability and genetic correlations for different brain regions,” recalled
Kristina Noreikiene, first author of the publication and Merilä’s PhD student.
Independent brain parts
“Our results suggest that neural tissue,
at least in sticklebacks, does not have severe genetic constraints and could, therefore, quickly respond to environmental demands through plasticity. This indeed may
be adaptive, especially in a rapidly changing and sometimes unpredictable world,”
Noreikiene explained. In contrast to the
brains of primates, rodents and birds, fish
brains show lifelong growth and neuro
genesis. The data also suggest an effect of
maternal influences on the brain size of offspring, which could stem from the quantity of nutrients deposited in the eggs or
other sources. The evolvability of different
Photos: James Mills, Nobertas Noreika
The creature is known for its complex
mating behaviour, which was described
by Nobel Prize Laureate Niko Tinbergen.
The male builds a nest from plant material, to which it lures the female by performing a zigzag courtship dance. After the female has deposited hundreds of eggs in the
nest, the male fertilises them. Male sticklebacks even guard and ventilate the eggs
and young. The BBC illustrated the dramatic love life of sticklebacks in a gripping
video: http://tinyurl.com/q9afsoy
Thus, threespine sticklebacks are
great animal models, also for brain
evolution. In one of his latest studies,
ecologist/evolutionary biologist, Juha
Merilä, discovered that additive genetic effects were responsible for about
40 per cent of the variation in the size
of the fish brain and its different regions. Surprisingly, he and his colleagues could not detect any impact
resulting from different rearing conditions (Proc R Soc B, 282:20151008).
For their brain evolution study,
the scientists from the University of
Helsinki and from the Eötvös Loránd Scientists in their outdoor lab:
University, Budapest, also acted as fish Juha Merilä and Kristina Noreikiene
LT_515_32_35.indd 32
Photo: www.publicdomainpictures.net/Petr Kratochvil
page 32
brain parts was moderate and the genetic
correlations among different brain regions
low. “Our data support the mosaic model of
brain evolution, according to which natural
selection can change brain areas fairly independently,” Merilä said. By contrast, brain
and body size were strongly genetically correlated in threespine sticklebacks and brain
size most likely evolved as a response to selection on body size.
For their experiments, the scientists fitted some of the labs’ aquaria with tubes and
artificial plants to provide a more complex
environment compared to plain aquaria.
Earlier studies with salmon had suggested
that a more stimulating environment, surprisingly even a single rock in the basin, influenced the size of the cerebellum. On the
contrary, this decoration did not produce
any major change in the size of the stickleback’s brain or its parts. There are, however, still some unknown factors, which were
not analysed, e.g. social interactions with
conspecifics.
Currently, Merilä’s group is performing quantitative trait locus mapping studies to identify the genomic regions relevant
to brain size variation. “Our main interest
is to see if the same phenotypes in different
stickleback populations are underlined by
different sets of genes,” he noted.
Tough times for basic research
The idea for the recently published
study came about by serendipity. Merilä’s grant-based position as an Academy Professor involves few teaching
and faculty tasks and, thus, allows him
to devote most of his time to the management of research projects. “I compensate for my reduced teaching obligations by supervising and mentoring
many PhD students and postdoctoral researchers,” he said. Additionally,
Merilä is a member of several review
and evaluation panels. In the past 15
years, science in Finland has profited
from a good funding situation. “Recently, the times have been getting
04/09/2015 09:41
Journal Club
5-2015
tougher for basic research as the Finnish
government has made some serious cuts
to the research and education budget,” the
ecologist noted. He worries about the many
young researchers who have to compete for
the few available permanent positions in
Finland.
Shortly before his departure to the
‘Eighth International Conference on Stickleback Behavior and Evolution’ at Stony
Brook University in New York, Merilä gave
Lab Times some insights into his career. “I
learned the fundamentals of evolutionary
biology as a PhD student at Uppsala University, Sweden,” the Finn recalled. “My scientific interests were inspired by the wonderful crowd of people at the old Zoology
Department. Further important influences were papers about natural selection and
quantitative genetics of wild populations by
Russell Lande, Arie van Noordwijk, Stevan
J. Arnold, Peter and Rosemary Grant and
their students,” he said.
From feathery to slippery
During his doctoral studies, Merilä participated in a long-term project investigat-
ing the inheritance and selection of quantitative traits in birds, which has been going on for more than three decades. “Most
of the individuals in the Collared Flycatcher population (Ficedula albicollis) on Gotland are now marked. The knowledge of
the pedigrees and generations of birds is
necessary for quantitative genetic studies,”
the researcher explained. In his analyses, he
increased and decreased clutch size and analysed whether this affected morphological
traits such as body size or genetic correlations between traits and their heritability. “I
observed that heritability was not constant.
It was lower when the environmental conditions were bad and, thus, reduced the expected evolutionary response to selection,”
he elaborated.
For his postdoctoral work he chose another research object. On his website he
commented on this transition: “After tramping the same trails in forests of the island
of Gotland for six years in a row banding
massive amounts of fluffy fledglings, I grew
to think that the grass could, after all, be
greener somewhere else. Hence, I regressed
to amphibians....” The ecologist investigat-
Lab Times
page 33
ed the adaptation of frogs to the acidification of water courses in Sweden, due to
environmental pollution and to enhanced
UV-B irradiation. “I was interested in the
heritability of tolerance traits,” he noted.
Into the wild!
His current research interests focus on
the mechanisms of animal adaptation to
local and changing environmental conditions. Together with his team at the Ecological Genetics Research Unit at the University of Helsinki, he is also analysing the relative roles of drift, phenotypic plasticity and
genes in differentiation among populations.
Field work is now mostly done by the
junior academic members. On rare occasions, however, the evolutionary biologist
manages to get out into the wild for research purposes, as the accompanying photo shows. But Merilä does not spend his entire time undertaking research on tiny fish,
birds and frogs. In his leisure-time, he is a
keen angler with a preference for really big
salmon.
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LT_515_32_35.indd 33
04/09/2015 09:41
page 34
Lab Times
Journal Club
5-2015
Plant Cytogenomics in Brno, Czech Republic
Treading in Mendel’s
Genomic Footsteps
Unusual chromosome numbers are a characteristic of North American rockcress
species. With a technique called comparative chromosome painting, Martin Lysak
and colleagues have revealed what lies behind this phenomenon.
P
lants have an extraordinary variety
of genome structures. Genomes vary,
for example, in their base chromosome numbers and ploidy (i.e. number of
chromosome sets), while individual chromosomes have different sizes, morphology
and composition. How are these genomescale differences linked to speciation, life
strategies, and the immense collection of
shapes and sizes of plant species? This is just
one question that fascinates Martin Lysak,
leader of Plant Cytogenomics research
group based at the Central European Institute of Technology (CEITEC), Masaryk University, in the city of Brno, Czech Republic.
constructed the evolutionary origin of the
Böcher’s rockcress (Boechera) genome.
They also revealed the formation of unusual chromosomes in apomictic rockcress
species (Plant J, 82(5): 785-93).
Boechera species are not easy to study,
as hybridization and apomixis are prominent in this genus. “Apomixis is a kind of
asexual clonal reproduction,” says Terezie
Mandáková. The apomictic forms are often
odd-numbered polyploids, e.g. with three
or five sets of chromosomes, while some
diploid Boechera apomicts are aneuploids,
i.e. have an uneven number of 15 chromosomes instead of the normal 14. “Chromosome pairing and meiosis in these plants is
problematic and leads to sterility. Apomixis
allows these aneuploid and odd-level polyploid plants to set seeds without fertilisation,” Mandáková explains.
Photos(2): Lysak lab
chromosomes, while their number can increase by fissions when a chromosome
breaks within the centromere.” What factors cause such rearrangements? “In nature, knowing the actual trigger is not easy.
There could be chemical or physical triggers, for example, UV radiation or temperature. Mobile DNA elements can also cause
chromosome rearrangements.”
To elucidate the origin of Boechera chromosomes, Martin Lysak and his team started to paint. Taking advantage of a technique called chromosome painting, Lysak
and his team marked conserved g
enomic
blocks on chromosomes and then compared these patterns to the so-called AnFrom Mendel’s peas to Böcher’s cress
cestral Crucifer Karyotype (ACK). “ACK is
Brno has a legacy of plant genomic
a theoretical concept resulting from mulresearch: the famous father of genetics,
tiple lines of evidence. The basic idea was
Gregor Mendel, carried out his pea-breedthat many present-day crucifer species have
ing studies in an Augustinian abbey in this
chromosome numbers based on eight. We
On the origin of chromosomes
very city. By the way, Brno is celebrating
hypothesised that also an ancestral genome
A species-specific set of chromosomes
the 150th anniversary of the publication of
could have eight chromosomes. Later on,
Mendel’s original observations this year! As
is called karyotype. “As single genes and
comparative genetic mapping and chromoa continuation in plant genetics,
some painting analyses showed
Lysak and his team aim to find
that some species (e.g. Arabidopout if chromosome rearrangesis lyrata, Capsella rubella) in difments influence plant genome
ferent genera have eight chromodiversification and speciation –
somes. These genomes represent
and whether this has any importhe ancestral genome still survivtance for evolution.
ing today,” explains Lysak.
Instead of peas, the Lysak
Arabidopsis thaliana, the first
lab’s model plants belong to the
plant species with a sequenced
mustard family, Brassicaceae,
genome, was also the first plant
also known as the crucifers acto have its chromosomes paintcording to the cross-like struced. This work was actually done
ture of the four petals in their Paint the lab red... green & yellow: Martin Lysak and Terezie Mandáková by Lysak himself, when he was
flowers. There are more than
working as a post-doc in the labwhole genomes, karyotypes are also sub3,500 Brassicaceae species distributed
oratory of Ingo Schubert at the Institute
jected to evolution,” explains Martin Lyworldwide, including several important
of Plant Genetics and Crop Plant Research
sak. “The structure of individual chromocrops and vegetables, such as canola, broc(IPK), Gatersleben, Germany. “We took adsomes can be altered by chromosome recoli, Brussels sprouts, cabbages and radish.
vantage of the sequenced A. thaliana gearrangements, such as inversions, transloIn the lab’s recently published research
nome and started to test whether libraries
cations and deletions. Some chromosome
article, Terezie Mandáková, postdoc in Lyof chromosome-specific BAC clones (Bacterearrangements, particularly chromosome
sak’s group, and Martin Lysak together with
rial Artificial Chromosomes) can be used to
translocations can reduce the number of
their Dutch and German collaborators, revisualise its chromosomes,” he tells.
LT_515_32_35.indd 34
04/09/2015 09:41
Journal Club
During the painting process, the DNA of
chromosome-specific BAC clones is isolated,
pooled and labelled by fluorochromes with
different emission spectra. These probes are
hybridised to target chromosomes with sufficient sequence similarity. Painting signals
are visualised and analysed using a top-end
fluorescence microscope. “First, we successfully painted a single chromosome and later on, the whole five-chromosome set of A.
thaliana. This was the first successful attempt to paint entire plant chromosomes,”
Lysak remembers.
In follow-up studies, the team tried to
see whether the Arabidopsis painting probes
could be used to identify homeologous
chromosome regions among other, closely
or more distantly related, crucifer species.
“It turned out that one can indeed identify
shared chromosomes and chromosome re-
Chromosome painting in the Alpine Pennycress. Differentially labelled painting probes
(red, yellow and green signals) identify particular chromosome regions.
gions, and thus, reconstruct the course of
evolution from common ancestral genomes
across the whole family,” Lysak says.
Solving the chromosome puzzle
Using this approach, the team was able
to solve the origin and structure of three
Boechera genomes (the sexually reproducing B. stricta, two apomicts B. divaricarpa
and B. polyantha) by colouring conserved
genomic blocks (GB) within individual
chromosomes. “GBs are chromosome segments, which are conserved in different
Brassicaceae species. They can be viewed
as some sort of building blocks, which are
rearranged to build up genomes of different structure,” explains the group leader.
The ancestral karyotype is divided into
24 GBs, spread on eight chromosomes.
Modern Boechera species ‘squeezed’ the
same number of blocks to only seven chromosomes. How did they do it? Mandáková
and colleagues showed that three Boechera
chromosomes kept their ancestral-like
5-2015
Lab Times
page 35
structure, while the remaining four underwent specific rearrangements. For instance,
the chromosome number was reduced
when one ancestral chromosome fused together with fragments of two other chromosomes, while one of the centromeres has become inactive and was eliminated.
The team obtained even more interesting results when looking at the origin
of unusual chromosomes present in apomictic Boechera plants. A larger chromosome, called Het, is found in diploid apomictic species like B. divaricarpa, while
two smaller ones, Het’ and Del, are present
in, for instance, B. polyantha, with an aneuploid (2n=15) chromosome number.
Het closely resembles one of the Boechera
stricta/divaricarpa chromosomes but has
longer stretches of heterochromatin around
its centromere. Why this accumulation has
happened and whether this is somehow
linked to the apomictic trait is a question,
still waiting to be answered.
Regarding the two tiny chromosomes
Het’ and Del, Terezie Mandáková and her
colleagues found an answer already. They
originated from the bigger Het chromosome through centromere breakage. This
breakage is the reason for the uneven number of chromosomes in B. polyantha, which
would normally cause trouble during meiosis. “Our study shows that extra chromosomes and, generally, certain types of chromosome rearrangements can become fixed
and be propagated to next generations due
to the apomictic mode of reproduction,”
says Lysak. Reproduction without sex does
seem to offer an escape route for plants
with chromosomes gone wild!
Future plan(t)s
This summer, Lysak’s team, in collaboration with Ute Kraemer from the Ruhr University Bochum, has published another interesting study on a different cress species
– the Alpine Pennycress (Noccaea or Thlaspi caerulescens). Chromosomes in this wellknown hyperaccumulator of heavy metals
have been altered by an unusually high
number of inversions, which could have facilitated the evolution of enhanced metal
homeostasis gene expression.
With important results like these, Martin Lysak’s research group, of course, continues their studies on the karyotype evolution in crucifers. Together with Duke University in the US, they are about to embark
on a bilateral project, focusing on many
more Boechera species native to North
America.
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LT_515_32_35.indd 35
04/09/2015 09:41
Lab Times
5-2015
Publication Analysis 2007-2013
Cell Biology
Ranking
Image: Heiti Paves/CC BY-SA 3.0
page 36
Microfilaments, mitochondria and
nucleus in fibroblast cells
Although Germany clearly leads the nations’ ranking, one French lab dominates European cell biology research.
Programmed cell death and stem cells are hot topics.
“F
or, as to the first, since our Microscope informs us that
the substance of Cork is altogether fill’d with Air, and
that that Air is perfectly enclosed in little Boxes or Cells
distinct from one another.” These famous words, uttered by Robert Hooke in 1664, weren’t perhaps the kick-off for cell biology
research as such but it, at least, gave the discipline its name: the
“little boxes” Hooke observed, reminded him of a cellula, a small
room. Hence, he named them “cells”.
Modern cell biology’s moments of glory came a few hundred years later. Especially in the 1960s and 70s, cell biologists churned out momentous discoveries about the cell. Micro
tubules, for instance, were first described in 1963 in hydra (JCB,
18(2):367-88) and in plant cells (JCB, 19(1):239-50). In the
same year, Margit and Sylvan Nass, back then at the WennerGren Institute for Experimental Biology in Stockholm, published
their findings on “intramitochondrial fibers with DNA characteristics” – the first description of mitochondrial DNA (JCB,
19(3):593-611).
Fifty years on, we know a cell inside out. Or do we? Cell biological research is still hotly debated. Just last year (LT 4-2014),
LT reporter, Karin Hollricher, unsuspectingly went to a scientific
conference on aneuploidy and got roped into a heated discussion
about mitosis. So, does research on mitosis attract the most citations? That’s what we will explore in this publication analysis.
No changes at the top
First, as you’ll perhaps know from past issues, we turn our
attention to Europe and the individual countries’ performance
in cell biology. For this, we rely on so-called expert journals, as
defined by Thomson Reuters’ Web of Science database. In the
last cell biology ranking from 2009 (LT 5-2009), covering papers, proceedings papers and reviews published between 1996
and 2007, Germany came out on top, followed by England and
France, Italy and Switzerland. Six years later, nothing much has
changed. As a matter of fact, the first 14 countries all kept their
positions. Only one country took a major step up the ranking ladder: Portugal climbed six spots from 23rd to 17th place. Comparing the average citations per article, Switzerland performed best
(42.7), followed by Scotland (36.6) and the Netherlands (36.4).
It’s also worth mentioning that cell biologically-themed articles
are, on average, cited twice as often as, for instance, articles on
reproductive biomedicine or parasitology, our last two publication analyses.
LT_515_36_39.indd 36
In the “battle” between Europe and the US, as usual, European cell biologists wrote more articles published in cell biology specialist journals. These articles, however, were cited less often than those penned by their US peers, in total (1,265,428 vs
1,649,744) and on average (26.7 vs 36.5).
Outside of Europe, Japan performed very well, scoring the
second most total citations; and Singapore, although not one
of the top nations when it comes to total citations, got ahead of
many others, even Germany and France, with their average citations per article (32.1).
So, what are then the most cited papers and reviews in cell
biology, published between 2007 and 2013? The undisputed
number one, with more than 8,000 citations to-date, is Douglas Hanahan’s and Robert Weinberg’s update article on the “Hallmarks of Cancer: The Next Generation”. In second place, Tony
Kouzarides informs the scientific community about chromatin
modifications and functions. Also among the top five articles are
two publications dealing with microRNAs. Interestingly, none of
the highly-cited articles is about those hot topics, which occupy
the majority of our most-cited cell biologists in Europe.
Hard to separate
This, eventually, brings us to the said top 30 list. Once again,
we had to come up with a few criteria to limit the vast amount
of researchers taking advantage of cell biological techniques, to
those, who can be considered true cell biologists. Not an easy
task, as we had to find out. While there are still many basic cellular mechanisms waiting to be fully elucidated, the best way to
attract many citations is to combine cell biology with other disciplines. Hence, many of our top 30 authors appeared in other rankings, too. Guido Kroemer, for instance, topped both the
Immunology and Cancer Research rankings. Boris Zhivotovsky
was among the top 30 in Toxicology Research and Maria Blasco
scored 9th place in the Ageing Research publication analysis.
So, we decided to include only those scientists, who published
a considerable number of their articles and reviews in cell biologically-themed specialist journals. In addition, ‘cell biology’ must
have been listed among the top two Web of Science categories for
a given scientist.
Interestingly, Europe’s top cell biologists are based in 13 different countries. England and France are home to five top cell
biologists each. The French mecca for cell biology seems to
be located in Villejuif, 7 km from the centre of Paris, in Guido
03/09/2015 14:38
Ranking
Kroemer’s lab, to be more precise. Including Kroemer (1st), four of
the five French cell biologists work or have worked there: Lorenzo
Galluzzi (6th), Maria Chiara Maiuri (21st) and Oliver Kepp (24th).
And what are they working on? Programmed cell death in
health and disease. Most of us are perhaps familiar with one way
for a cell to die by choice – apoptosis – but there are many other
death strategies, such as autophagic cell death, programmed necrosis, mitotic catastrophe and entosis (cellular cannibalism) as
Kroemer informs on his website. Hence, one of his goals and that
of his lab fellows is to “resolve the fundamental enigma: through
which molecular and cellular mechanisms do cells die in normal
tissue”. In cancer cells, however, these vital ways to bite the dust
voluntarily are severely disturbed. Kroemer, thus, “launched a
quest into the mechanisms that determine cell death resistance or
connect different cell death modalities in cancer cells”.
Cell death, stem cells and enzymes
The four French aren’t, however, the only ones interested in a
cell’s final moments; also David Rubinsztein (4th), Peter Vandenabeele (8th), Gerry Melino (16th), Mauro Piacentini (18th), Boris
Zhivotovsky (25th) and Terje Johansen (30th) all study cell death.
Stem cells, on the other hand, usually mark the beginning of
a cell’s life cycle. Hans Clevers (2nd); Austin Smith (20th); JuanCarlos Belmonte (27th) and Hendrick Stunnenberg (29th) have
dedicated their professional lives to these undifferentiated cells.
Directing the Center of Regenerative Medicine in Barcelona for
many years, Juan-Carlos Belmonte has, in the meantime, transferred his office fully to the Salk Institute for Biological Studies in
San Diego. While still in Spain, his lab made major headlines with
“mini-kidneys” grown from human pluripotent stem cells (Nature
Cell Biol, 15:1507-15).
Between birth and death, a cell’s life is full of action. Johan
Auwerx (9th), for instance, wants to decipher metabolic pathways; Carlos Lopez-Otin (10th) has zeroed in on novel human proteases, such as metalloproteinases of the MMP and ADAMTS family, as well as serine and cysteine proteases. Benoit Viollet (12th)
focusses on different but not less important enzymes, the energy
sensor AMP-activated protein kinases. Ivan Dikic (22nd), on the
other hand, follows the ubiquitin pathways to learn how they regulate endocytosis, immune responses, DNA repair and proteasomal degradation.
Last but not least, a few top 30 cell biologists have a weakness
for a cell’s genetic material. Jiri Bartek (17th) in the Prague-based
Laboratory of Genome Integrity wants to understand the DNA
damage response and DNA double strand breaks. Telomeres and
their role in ageing and cancer are Maria Blasco’s (19th) scientific passion.
What’s the future of cell biology? Will it merge with other disciplines like oncology or immunology and disappear from the scientific world stage? Or will it perhaps just take a new direction? In
a 2010 contribution to Molecular Biology of the Cell (21(22):3822),
Kai Simons, former director of the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden, Germany, gazes into
the crystal ball, “I predict that engineers, who today lack training
or knowledge of cell biology, will in the future take their inspiration from all the wonder machines that nature has produced. Molecular cell biologists are continuously unravelling the workings of
the cellular nanomachineries. This will be a real source of future
welfare and wealth globally, and not like the virtual dividends
that result from manipulating the financial markets.”
Kathleen Gransalke
LT_515_36_39.indd 37
5-2015
.
Lab Times
page 37
Europe...
Country
Citations
Articles
Cit./Art.
1. Germany
2. England
3. France
4. Italy
5. Switzerland
6. Netherlands
7. Spain
8. Sweden
9. Scotland
10. Israel
11. Belgium
12. Austria
13. Denmark
14. Finland
15. Norway
16. Poland
17. Portugal
18. Ireland
19. Hungary
20. Czech Rep.
332,217
272,709
193,619
150,860
107,965
106,879
91,608
62,306
59,211
49,425
49,373
39,705
36,798
30,381
21,890
18,439
17,829
17,447
15,339
14,644
10,803
7,957
6,103
6,107
2,526
2,933
3,818
2,040
1,619
1,479
1,463
1,324
1,111
934
689
1,530
717
653
631
700
30.8
34.3
31.7
24.7
42.7
36.4
24.0
30.5
36.6
33.4
33.8
30.0
33.1
32.5
31.8
12.1
24.9
26.7
24.3
20.9
Articles appearing between 2007 and 2013 in ‘Cell Biology’ journals as listed by SCImago and Thomson Reuters’ Web of Science. The citation numbers are accurate as of July 2015. A country’s figures are derived from articles, where at least one author
working in the respective European nation is included in the authors’ list. Israel is included because it is a member of many European research organisations and programmes (EMBO, FP7 of
the EU...).
... and the World
Citations
Articles
Cit./Art.
Europe
1,265,428
47,312
26.7
USA
Japan
China
Canada
Australia
South Korea
1,649,744
251,505
179,933
161,045
100,926
70,329
45,174
10,653
11,538
5,826
3,402
4,269
36.5
23.6
15.6
27.6
29.7
16.5
03/09/2015 14:38
page 38
Lab Times
Ranking
5-2015
Publication Analysis 2007-2013 – Cell Biology
Most Cited Authors...
Cit- Artations icles
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
Guido Kroemer, Inst Gustave Roussy, Villejuif
Hans Clevers, Hubrecht Inst, Utrecht
Jürg Tschopp, Univ Lausanne, † 22.03.2011
David C. Rubinsztein, Med Genet, Univ Cambridge
Douglas Hanahan, Swiss Inst Expt Canc Res, Lausanne
Lorenzo Galluzzi, Inst Gustave Roussy, Villejuif
Peter Carmeliet, VIB Vesalius Res Ctr, KU Leuven
Peter Vandenabeele, VIB Inflamm Res Ctr, Univ Ghent
Johan Auwerx, Lab Integrat & Syst Physiol, EPFL, Lausanne
Carlos Lopez-Otin, Biochem & Mol Biol, Univ Oviedo
Kari Alitalo, Inst Biomed, Univ Helsinki
Benoit Viollet, Inst Cochin,Univ Paris
Michael P. Lisanti, Inst Canc Sci, Univ Manchester
Jiri Friml, Inst Sci & Technol, Klosterneuburg
Josef M. Penninger, Inst Mol Biotechnol, Vienna
Gerry Melino, Toxicol, Univ Leicester
Jiri Bartek, Inst Mol Genet, Prague
Mauro Piacentini, Biol, Univ Rome
Maria A. Blasco, Mol Oncol, Spanish Natl Canc Res Ctr, Madrid
Austin G. Smith, Stem Cell Inst, Univ Cambridge
Maria Chiara Maiuri, Inst Gustave Roussy, Villejuif
Ivan Dikic, Biochem, Univ Frankfurt
Tony Kouzarides, Gurdon Inst, Univ Cambridge
Oliver Kepp, Inst Gustave Roussy, Villejuif
Boris Zhivotovsky, Toxicol, Karolinska Inst, Stockholm
Dario R. Alessi, Coll Life Sci, Univ Dundee
Juan-Carlos I. Belmonte, Ctr Regenerat Med, Barcelona
Reinhard Fässler, Mol Med, Max Planck Inst Biochem, Martinsried
Hendrik G. Stunnenberg, Mol Biol, Radboud Univ Nijmegen
Terje Johansen, Med Biol, Univ TromsØ
... and Papers
32,352
15,248
15,001
12,655
12,597
11,390
10,124
9,336
8,663
8,477
8,008
7,473
7,459
7,255
7,181
7,126
7,123
7,072
7,071
7,056
7,004
6,878
6,659
6,521
6,312
6,286
6,267
6,155
6,149
6,103
312
149
99
107
38
131
197
115
120
108
131
146
217
112
167
161
98
75
89
60
48
80
27
94
81
78
116
107
105
37
Guido Kroemer (1.)
David Rubinsztein (4.)
Douglas Hanahan (5.)
Carlos Lopez-Otin (10.)
Jiri Bartek (17.)
Maria Blasco (19.)
Ivan Dikic (22.)
Terje Johansen (30.)
Citations of articles published between 2007 and 2013
were recorded up until May 2015 using the Web of Science database from Thomson Reuters. The “most-cited papers” had correspondence addresses in Europe or Israel.
1. Hanahan, D; Weinberg, RA
Hallmarks of Cancer: The Next Generation
CELL 144(5): 646-674 MAR 4 2011
2. Kouzarides, T
Chromatin modifications and their function
CELL 128(4): 693-705 FEB 23 2007
3. Valadi, H; Ekstrom, K; Bossios, A; Sjostrand, M; Lee, JJ Lotvall, JO
Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells
NATURE CELL BIOLOGY 9(6): 654-U72 JUN 2007
4. Haass, C; Selkoe, DJ
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer’s amyloid beta-peptide
NATURE REVIEWS MOLECULAR CELL BIOLOGY 8(2): 101-112 FEB 2007
5. Landgraf, P; Rusu, M; Sheridan, R; [...] Sander, C; Zavolan, M; Tuschl, T
A mammalian microRNA expression atlas based on small RNA library sequencing
CELL 129(7): 1401-1414 JUN 29 2007
LT_515_36_39.indd 38
Citations
8,222
4,067
1,979
1,833
1,770
03/09/2015 14:38
Opinion
5-2015
Lab Times
page 39
What’s behind paper retractions? (30)
Want to End Fake Peer Reviews?
Retraction Watch’s Adam Marcus and Ivan Oransky tell you how easily it
can be done.
B
Shockingly simple
Photo: Photocase/zettberlin
y now, you may have heard about a
relatively new – but alarming – phenomenon: researchers figuring out
how to get their papers published without
true peer review. In August, Springer announced it was retracting 64 papers for this
reason, while SAGE said it was retracting 17.
At the time of this writing, publishers have
retracted 250 papers since 2012 because
authors either did their own peer review or
had others do the peer review, sometimes
unbeknownst to them.
How did this happen? (“And why didn’t I
think of it?,” you’re probably muttering.) The answer is: quite easily. Indeed, gaming the peer
review system turns out
to be shockingly simple
to do – and just as easy to
prevent.
As we’ve recounted
elsewhere (Nature, November 26th, 2015, Publishing: The peer-review
scam), when journal editors ask authors to suggest potential reviewers
for their manuscripts, the
authors provide names,
“sometimes of real scientists and sometimes
pseudonyms, often with bogus e-mail addresses that would go directly to him or his
colleagues”.
A vulnerable editorial system
The problem has affected major publishers, from Elsevier to Springer to Wiley.
The most recent cases were from China and
Iran, but the practice has also been found
in South Korea and Pakistan. What the cases have in common are two factors: one,
editors asked authors to suggest reviewers
when they submitted the papers; two, the
people submitting the papers – who were
not always the authors – were able to enter
fake email addresses for those suggested reviewers, or reassign reviewers, without editors knowing, thanks to the particular editorial systems those publishers use.
LT_515_36_39.indd 39
Thankfully, that makes eliminating the
problem fairly straightforward. For one,
journals could stop asking authors to recommend reviewers – or do as some editors
do and use those lists to eliminate possible reviewers, figuring they were chosen
because they wouldn’t be terribly critical.
Some editors may insist that the hyper-specialisation of their fields makes asking for
suggested reviewers necessary. That’s fair
enough and it’s also a strong argument for
implementing the second way to end fake
peer reviewers – namely, doing more to verify
digital identities.
Currently, journals
(like anyone else at the
other end of an electronic exchange) can’t
be sure that an author
or reviewer is who she
says she is (although,
in the case of research
misconduct, most malefactors are male.) The
systems for collecting
peer reviews that journals use could close the
loophole by forcing editors to verify entered
email addresses, or,
even better, requiring
them to connect with the ORCID database
of authors to validate identities.
What’s the next big scam?
Of course, fraudsters are clever and
they’re probably already thinking about –
or even implementing – the next big scam.
And other hoaxers, trying to expose the lack
of peer review at some journals, have managed to get completely fake papers published. We’d need to eliminate the causes
of this kind of fraud – pressures to publish
or perish come to mind – to really end such
scams. But taking these initial steps can’t
hurt.
Adam Marcus and Ivan Oransky
(The authors run the blog Retraction
Watch: http://retractionwatch.com)
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03/09/2015 14:38
A Veritable Niche
Poland, with a population of 38.5 million, houses far less than 100 biotech
companies. That is just a sixth of the
number in Germany (about 580 companies) and a tenth of the UK’s biotech
companies number (over 900). Even
Poland’s eastern European neighbours,
such as Hungary, are further developed
when it comes to biotechnology.
Nevertheless, there are bright spots,
such as the Selvita Group with headquarters in Krakow. For the first half-year
of 2015, they have reported a pretty
respectable operating profit of €5.8 million. And compared to the first half-year
of 2014, the group’s revenues even experienced 34 percent growth. According
to Selvita, this is the third consecutive
six-month period with an operating profit.
Selvita is almost unknown in Western
Europe. The company, founded in 2007,
researches oncology drugs, currently employing over 230 scientists, with offices
near Boston, USA and Cambridge, UK.
Their first candidate is SEL24, an
orally-administrable small molecule. It
works as a selective inhibitor of PIM and
FLT3 kinases. Potential applications could
be acute myeloid leukemia (AML), nonHodgkin’s lymphoma and multiple myeloma. At the end of March 2015, Selvita
signed a service agreement with US pharmaceutical services company, Aptuit, for
the preparation of selected studies.
But the promising financial data have
a different cause: Selvita also provides
integrated drug discovery, chemistry
and biology services. The company offers pharmacodynamic in vitro studies
to analyse biosimilar products’ activities
in comparison to reference compounds.
Generic approval of this area is becoming
increasingly important. Health systems
can achieve immense savings by using
generic drugs. That registration trials outside the EU can become problematic was
recently shown in the scandal over falsified data at GVK Biosciences, an Indian
company (see Lab Times 1/2015, page
35: “Fishy Trials”). In addition to its own
research projects, Selvita has thus found
a veritable niche.
-MvdH-
Funding: CRISPR/Cas9 on the advance
Flushing Cash
into Coffers
a Series A investment round. That is a good
portion less than across the ocean but more
than enough to start drug development operations.
Michael van den Heuvel
UK: Shire plans next billion takeover
CRISPR/Cas9 pioneer Emanuelle Charpentier (left) has so far raised €102 million to
push the revolutionary gene-editing technology with CRISPR Therapeutics (Basel, Switzerland), while her former colleague Jennifer Doudna collected €145 million for her USbased startup, Editas Medicine.
CRISPR/Cas9, a new and promising geneediting technique, has revolutionised genetic engineering since August 2012 – not only
in academia but also in industry. This astonishingly successful method raises hopes for
the far more rapid and easier development
of new drugs and therapies. One of the most
important CRISPR/Cas9 companies has
once again collected huge sums of capital:
Editas Medicine received a further €107 million from a group of investors. The US company wants to use CRISPR/Cas9 technology
to develop drugs against cancer, retinal disease and sickle cell disease, among others.
The new financing round was led by
Boris Nikolic, former chief advisor on Science and Technology at the Bill & Melinda
Gates Foundation and now managing director of an investment company with the
strange name of Bng0. Gates is also among
the new investors, as well as a number of
other wealthy people who want to remain
anonymous. Editas had previously received
€38 million in capital and is one of a number of non-listed biotech companies that
collect a lot of money for advanced genetic
therapies in the United States.
But what about European CRISPR/Cas9
competitors? Are they also bathing in funding capital like their US counterparts? It
looks that way. CRISPR Therapeutics, located in Basel, Switzerland, has also successfully raised funds several times. At the
end of April 2015, the company announced
the closure of a Series A and Series B financing totalling nearly €80 million. The year
before, they raised another €22 million in
Fusion Replaces
Innovation
The Ireland-based pharmaceutical manufacturer Shire wants to swallow its US rival Baxalta for €27 billion. The project is
likely to go ahead despite resistance from
Baxalta management, Shire announced.
Shire’s CEO Flemming Ornskov wants to
use the acquisition to transform his company into a global group, specialised in medicines for complaints like blood diseases,
cancer and immunological illnesses.
Photo: Shire
Po lan d : Selv i ta o n th e r i se
LT_515 Business.indd 40
Biobusiness
5-2015
Photo: Cailey Cotner/UC Berkeley
Lab Times
Photo: Helmholtz/Hallbauer&Fioretti
page 40
The 57-year-old Dane, Flemming Ornskov,
Shire’s Chief Executive Officer since April
2013, is going to make the Ireland-based
drug maker a big player. But is he also capable of contributing real inventiveness?
This has been a fairly common strategy amongst large drug manufacturers for
many years: Lack of inventiveness will be
offset by the acquisition of other companies.
This need is also driven by high research
costs and by the expiration of patents. In
July, Shire sent its original offer to Baxalta
but without success. Ornskov then decided
to contact shareholders directly. The management has offered Baxalta shareholders
a premium over the closing price of their
shares on August 3, 2015. After a successful
merger, Baxalta shareholders would hold
approximately 37 per cent of the new group.
At the time of the bid, Baxalta was valued at
$45.23 (about €40) per share.
Baxalta has only been on its own for a
few weeks, after the company was cleaved
from the US medical technology company
Baxter. Baxalta currently has 16,000 employees with an annual revenue of around
€5.3 billion. Shire has 5,300 employees,
with an annual revenue in the same range
as Baxalta’s.
03.09.15 12:47
Biobusiness
UK: Parexel dismisses employees… again
Made in Vain
In December 2014,
British pharmaceutical company, GlaxoSmithKline (GSK),
announced a restructuring that affected
the Research Triangle Park in North Carolina, USA, causing
some 900 employees
to lose their jobs. Many research and development activities were
shut down. A possible reason: None of the biggest blockbusters
made it through Phase III trials. Fortunately for the dismissed
workers, GSK signed an agreement with a multinational contract
research organisation (CRO), Parexel, to create a new sub-unit.
500 of the endangered GSK jobs were transferred to Parexel.
But these positions were a poor match. The tide has turned
again, and Parexel has announced that it will cut as many as 850
jobs, starting this year and ending mid-2016; 125 of the layoffs affect the beleaguered ex-GSK staffers. The cuts will be implemented worldwide. The background: R&D activities have declined in
the industry, and fewer firms are using CROs like Parexel.
But the board of directors still has an option left. In April 2015
Parexel acquired Quantum Solutions India, which provides specialised pharmacovigilance services. This will enhance Parexel’s ability to deal with the adverse effects of new pharmaceutical
products. Is it inappropriate to ask whether they will soon shift
some former GSK jobs to India?
Biosimilar naming
Same but Different
The name “biosimilar” already implies its meaning: The relevant
drug is estimated to be similar but not identical to the reference
product. Being synthesised in organisms or cells, there’s a problem: Different cell lines as well as slightly variant culture media
can cause marginal differences, resulting in less effective or even ineffective copy drugs.
Patient safety organisations and reference drug
firms have long been demanding different generic
names for biosimilars to ensure patient safety and
correct side effect reporting. Now they have succeeded. Recently, the first biosimilar made its debut
The original...
on the US market (the granulocyte-colony stimulating factor Zarzio, made by Sandoz), and the authorising authority in charge, the FDA, proposed a four letter suffix for the generic name of both the reference and the biosimilar product (see “Nonproprietary Naming of Biological Products
Guidance for Industry“ at www.fda.gov/downloads).
The FDA’s attempt implies an unwieldy new nomenclature.
Amgen’s reference product, Neupogen, for example, would carry
the byname “filgrastim-jcwp” while Zarzio would be “filgrastimbflm”. The same-day statement of Bertrand Liang, chairman of
the Biosimilars Council, already gives a foretaste of an upcoming
lively debate, “Adding a random collection of letters to the product’s nonproprietary name confers no additional safety benefit,
5-2015
Lab Times
page 41
and in fact would require
the healthcare professional to be armed at all
times with a code-breaking reference”.
...and the biosimilar copy.
Nice wording, but what
Liang probably wanted to say is that the new FDA regulation is
jcwp-bflm – or, in short, bullshit.
Lucie Proksch
Biogen to build huge factory in Solothurn
Dawn of the
Excavators
US biotech giant Biogen is to invest €920
million in Switzerland.The US-headquartered company aims to build a huge production plant for biopharmaceutical drugs
in Luterbach (Canton Solothurn, not far from the Basel area),
Biogen’s officials announced in July. After the buildings are finished in 2019, they will
house up to 400 employees.
Biogen develops therapies for the treatment of
neurodegenerative, hematologic and autoimmune diseases, such as the
groundbreaking MS drug
Tecfidera which earned revenues of almost €2 billion
alone in 2014. In total, the
Biogen and Swiss officials signing
US group’s 7,500 employthe contract for the building project
ees generated €9 billion last
year, with a whopping profit of €2.7 billion. And Biogen is still
on the run: A novel drug candidate to treat Alzheimer’s patients,
Aducanumab, is currently being investigated in phase II trials. According to study data, the therapeutic antibody successfully targets and removes aggregated forms of beta amyloid.
Few are aware that Biogen’s roots lie in Switzerland. The organisation was founded in Geneva in 1978 by a group of biologists including the later Nobel laureates, Walter Gilbert und Philip
-wkSharp, and moved its headquarters to the US in 1982.
03.09.15 12:47
Lab Times
Biobusiness
5-2015
Photo: Fotolia/Dmytro Sukharevskyy
page 42
Mitochondrial replacement therapy (MRT) under fire
A Showcase for Public
Engagement with Science?
The clinical introduction of Mitochondrial Replacement Therapy (MRT) in the United Kingdom could allow
women, carrying pathogenic mitochondrial mutations, to have genetically-related but healthy babies. MRT has,
therefore, been hailed a success story of science engaging with the public. Klaus Reinhardt provides an opposing personal view.
A
notable day: On 3rd February 2015,
members of the British Parliament
(MPs) voted in support of allowing
legislation to introduce clinical application of Mitochondrial Replacement Therapy (MRT), also dubbed the three-parent baby technology. Followed by a similar vote in the House of Lords, legislation
now proceeds.
Mark Henderson, head of communications at the Wellcome Trust, that funded
research into MRT and its publicising over
several years, called the public debate preceding the vote a success story of communicating science to the public. I wonder how
many MPs, how many patient organisations
and how many of the 40 prominent scientists that supported the immediate clinical
introduction of MRT, rather than supporting further research before its introduction, knew that the evidence for the safety
of MRT is based on trials involving oocytes
from only 15 human individuals, three macaques and ten mice.
Henderson’s phrasing that a battle has
been won (Guardian, 5th Feb 2015) raises two questions: Who was the enemy –
technophobic, progress-avoiding, pro-life
treatment deniers? And how was the battle fought?
One strategy in the battle was to replace
“oocyte nuclear transfer” with “mitochondrial donation”. “Oocyte nuclear transfer”
was probably too close to “somatic cell nuclear transfer” (SCNT), employed to create
Dolly the sheep.
A battle has been won. Really?
“Oocyte nuclear transfer” is, however,
what actually happens during MRT, not mitochondrial donation. The nucleus is placed
alongside novel mitochondria and cytoplasm in the enucleated donor oocyte. The
altruistic “donation” demonstrates MRT’s
good intentions. But do we know as much
about MRT as about organ donation to warrant it being communicated like this?
No.
Was the British government organisation in charge, the Human Fertilisation
and Embryology Authority (HFEA), justified in stating that SCNT results are irrelevant because nuclear transfer between somatic cells is not comparable to placement
into germ cells? Or was this argument a hybrid between evidence and the battle that
needed to be won?
This will be difficult to determine. But
using other criteria for science communication with the public, I oppose Henderson and argue that the debate has failed in
many aspects.
Treating evidence
Technology promising healthy children
to suffering mothers creates high hopes
but disappointments would be particularly painful. Even rare or small risks would
concern individuals. Communicating that a
technology alters heritable material – thereby crossing one of the few red lines that humankind agrees about – would require a
03.09.15 12:47
Biobusiness
Placing the nucleus: without risk?
HFEA provides two reasons:
1) interactions between specific mitochondrial and nuclear alleles (mito-nuclear interactions, MNI) cannot be important
because sexual reproduction generates as
many novel MNI as MRT does,
2) negative consequences of MNI only
came from inbred animal lines.
Known to HFEA (and also the Science
and Technology Committee of the British
parliament), the latter statement was incorrect (www.plosgenetics.org/annotation/listThread.action?root=80535).
Why reason 1) is also wrong was
explained in a paper (Science 341
(2013):1345) that HFEA dismissed within hours of its publication (www.hfea.gov.
uk/8178.html). HFEA and the IRP ignore
the fact that 100% of the nuclear genome
is new to all mitochondria during MRT but
only 50% is new in sexual reproduction.
And that’s the successful 50% of alleles that
had allowed the mother to reproduce.
HFEA suggested that mixed-race children do not perform worse than other chil-
dren, so the nucleus can’t have problems
with foreign mitochondria. HFEA should
be reminded that mixed-race children also
have mothers, who inherit 50% of their genome to their children. The head of the
Wellcome Trust, infection disease specialist, Jeremy Farrar, had not understood this
problem either but thought he had and
joked about it as late as two days before
the vote in Parliament
(https://twitter.com/jeremyfarrar/status/561478
338104287233?refsrc=e
mail&s=11).
Lab Times
page 43
for the pathogenic mutation). Such recommendations were not made by HFEA. Instead, its former chief calls safety concerns
a “red herring”.
The IRP suggests that MNI are of no
concern because the molecular mechanism
causing phenotypic effects in mismatched
mito-nuclear pairings are not known. This
ignores empirical evidence in favour of
Considering evolutionary data to be irreleMitochondrial Replacement Therapy (MRT)
vant may be caused by the
biomedical focus of IRP
(and HFEA) members.
Did IRP and HFEA, then, critically consider
theoretical considerations. It may be jusbiomedical studies on MNI? I suggest not.
tified but not with the theoretical argu MRT treatment effects in flagship
ment provided:
studies were overlooked (EMBO Rep (2015)
“…assume that a child born after MR
embr.201439110).
has slightly different energy metabolism
 Most oocytes were from the same docompared to his or her parents. Will this
nors preventing cross-individual (epidemiomatter? Assuming the child is healthy, I
logical) risk predictions.
very much doubt it will concern anyone.”
 Disappointing! An afternoon’s search
(New Scientist, 17th Oct 2014). The IRP is
free
to call differences of up to 20% “slight”.
in the medical literature by an evolutionary
I had seen a quantification of metabolic efbiology colleague of mine produced at least
fects from published studies as the IRP’s job
15 papers reporting MNI, including in Gene
before any communication. Moreover, asand Trends Mol Med. One showed a highsuming a priori that a child will be healthy,
er prevalence of Parkinson’s disease for mt
when actually this was the matter to be
haplotypes carriers other than haplotype J
studied, is as far removed from good sciMark Henderson
ence (communication) as I can imagine.
(Wellcome Trust)
(The American Journal of Human Genetics
(2003) 72: 804). Therefore, if the donor’s
mitochondria are not of haplotype J, MRT
might result in a higher likelihood that offspring will develop Parkinson’s disease.
Far removed from good science
Other studies show interactions between more specific loci of the mt and the
nuclear genome (e.g., Human Molecular
Genetics (2014) 23: 3527) that could not
be met by haplotype matching. Donor and
recipient’s compatibility will be guaranteed if their mt genomes are identical (safe
Illustration: OHSU
Overlooked effects
Photo: Worfolk Lectures
particularly stringent examination of the
available evidence. Was the Independent
Review Panel (IRP) created to assess existing evidence the stringent examiner?
No.
Studying epistatic interactions between mitochondrial and nuclear genomes in animals, evolutionary biologists have
screened 27,000 offspring from 3,000 putatively healthy, maternal subjects of several species (about 15 papers, see Science
341 (2013):1345). The offspring phenotype depends on specific combinations
of mitochondrial and nuclear genomes.
Health consequences occurred more often
with novel mtDNA than with original (or
some control) mtDNA, resulting in reduced
fertility, accelerated ageing, developmental, respiratory and cognitive impairment.
These symptoms are a small risk for sufferers of devastating forms of mitochondrial diseases.
For mutation carriers, whose offspring
do not express the disease (19 in 20 to 49
in 50) and so may be treated unnecessarily, these symptoms may be a consideration.
How can this data justify HFEA’s communication to the public that placing the nucleus
(of a usually asymptomatic woman carrying
a mitochondrial mutation) into the cytoplasm of a randomly chosen donor is without risk for the resulting offspring? (Later,
some kind of haplotype matching was proposed – see below).
5-2015
Addressing economic interests
In an ideal world, the research interest
of the laboratory would be detached from
universities’ interests in performing clinical
MRT. The downside of this is that expertise
is inevitably lost. Private economic interests
also exist for the immediate clinical introduction of MRT. In one case, these interests
were originally not declared, yet safety concerns were dismissed and, instead, it was
suggested that reproductive treatments had
always represented a risk for affected families (PLoS Genetics (2014) 10:e1004315).
This publication’s editor had been a co-author within the last two years – nothing to
convince me of an apparent showcase on
how science should influence society.
Calculating incidences
The majority of mutation carriers will
have offspring that are not severely affected. Desirably, the number of sub-
03.09.15 12:47
page 44
Lab Times
Biobusiness
5-2015
jects treated unnecessarily should be low.
I would have, therefore, expected the IRP
to review from published studies the incidence of MNI after mitochondrial transfer.
My own preliminary, unpublished analysis
place the incidence of negative effects of
MNI as high as one in 27 maternal subjects
(calculated from the studies listed in Science
(2013) 341:1345).
Unless the number is wildly off, it confirms the obvious – that the majority of off-
one healthy person resulting from accidental MRT as evidence that problems are unlikely – as done by the BBC and editorials in the highest-profile science journals
– is not.
Extra caution for heritable alterations
Altering inherited material in humans
will be controversial, no doubt. Extra caution, such as the application of exaggerated
safety standards may be useful to broaden
If something goes wrong, serious side effects
(right) are an undesirable result
be upheld after proponents of the immediate clinical introduction of MRT suggested
that, per year, 150 women at risk of mitochondrial diseases could benefit from MRT
(NEJM (2015), 372: 885)? And is the conclusion by the BBC (published one week
before the vote by MPs) extra careful that
annually 150 three-parent babies could be
born? Or would responsible communication rather have included the notion that
the 150 women at risk include about 100
asymptomatic, first-degree relatives and
women, whose offspring will have mild
symptoms (some of which may not need
the therapy)?
Photo: Aliaksei Lasevich/Fotolia
Is “easily passing” a quality feature?
spring born after MRT are expected to be
healthy. It also suggests that the total number of 28 maternal subjects examined to
date could statistically have revealed only
one case of mismatch. We may see more
(EMBO Reports (2015) embr.201439110).
Carrying out a risk analysis and explaining it to the public would have been responsible science communication. Using
the consensus. It is not extra caution, when
currently HFEA and IRP consider five studies that report no side effects (ignoring actual treatment effects – see above) as safety-relevant but consider about 30 studies as
irrelevant that do show MNI.
HFEA suggested introducing MRT for
women who have a history of children
with diseases. Will this careful approach
“…building a winning coalition of support for mitochondrial donation” (Mark
Henderson) is important. How the battle
was fought, we have seen. But who was
the enemy? I doubt that the available evidence will allow the conclusion that calls
for an immediate clinical introduction of
MRT are morally superior to calls for further research. “That mitochondrial donation has passed so easily through the Commons […] shows how this engagement can
benefit science, as well as society” and, “will
have a direct impact on the lives of families
affected by a devastating disease” – Henderson, of course, knows how to make his
case in the media.
However, such communications easily
nourish hope and influence MPs and Peers
– all necessarily non-experts – and should
have been based on underlying evidence.
Scientific evidence would have been a superior advisor to MPs than the “national
sense of pride” (Science (2015) 348:178).
Klaus Reinhardt
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03.09.15 12:47
Biobusiness
5-2015
Lab Times
page 45
Possibly edible insects,
investigated at Zetadec
Developing offbeat food source solutions: Zetadec, Wageningen (The Netherlands)
The Bug Track
A five-member start-up, located in the Dutch centre of life science
and research, is pursuing exceptional approaches for the feed industry.
A
rriving in the Wageningen business
park, Zetadec B.V. is not easy to find.
Like many other small biotech startup companies it is located in a huge grey
building with lettering heralding “AGRO
BTC” above the main entrance. Two information boards listing all of the companies
located here are standing to the side, their
names given in tiny letters, hardly visible to
the wandering visitor.
After going inside and being welcomed
by the receptionist, I make the acquaintance of Oriane Guerin and her colleagues.
She excuses the unexpected absence of the
company’s boss, Menno Thomas. Unfortunately, Thomas broke his foot motorcycling
on vacation and comes in only for a moment to pick up some important work, before proceeding to the colloquium of his
master student, Guizhao, who is doing an
internship at Zetadec.
Mid August is vacation season in the
Netherlands, so it is nearly impossible to
meet the entire staff of any firm. At Zetadec,
some staffers are still enjoying their holidays, like Marcel van Culembourg and Frederiek Simons, both MScs in agrotechnology
and plant sciences, respectively. The two
work at Zetadec on, amongst other things,
sustainable feed production and application strategies. The other three colleagues,
pictured below, can be met personally, putting faces to the international backgrounds
of this start-up venture.
Zetadec’s founder, Menno Thomas (the
injured company leader), completed his
PhD in Wageningen in 1998, researching
the physical quality of pelleted feed. After a
couple of years working in the industry, he
decided to found his own company in 2007.
Zetadec’s name is taken from a French
sawmill (Ets Zetadec). Thomas stum-
Liya Yi, Oriane Guerin and master student,
Guizhao (from left), discussing their last
experiment and obviously having fun in
their office at Wageningen business park.
03.09.15 12:47
Lab Times
5-2015
bled upon the sawmill whilst doing practicals in France around 1987. When the time
came to start his own “consultancy and contract R&D organisation for the feed, food
and biomass industry“, the name stuck and
so it became Zetadec B.V.
What is Zetadec’s core business? The
Dutch company assists their industrial clients in developing formula and recipes for
new foodstuffs, as well as testing the functionality of ingredients and performing
lab-scale to full-scale operation tests. They,
“conceptualise new food product lines for
new products, and enhance the performance of existing production lines”.
For this purpose, they own two lab
units: one is for product development,
equipped with wet-chemistry analytical
tools, and the other is used for developing
milling, extruding, granulating and coating procedures in pilot experiments before
upscaling.
Improving food quality
Zetadec’s other main aim is to improve
the quality of feed and food stuff. Thomas
and his co-workers are working, for example, on the optimisation and improvement
of starch gelatinisation and protein denaturation processes. Biomass can be converted to biofuels or bioplastics by thermal,
chemical or biochemical processing strategies. Calculations of the energy balance
based on specific electric and thermal energy (SME and STE) consumption figures are
performed. Zetadec is a research partner
in the French “Equienergie” project, led by
Liya Yi with her
recently
accomplished
PhD thesis.
Her knowledge
of insects
is now
rewarded
at Zetadec
Biobusiness
GreenResearch, and also participates
in a SBIR (Small Business Innovation
Research) programme for agrologistic and biomass from the Biobased
Economy. Since process optimisation
and statistical analysis of big data in
bioscience is nowadays increasingly
important, Zetadec is also focusing
on that by developing new client-oriented solutions.
The goal of the company is to create a link between raw material and
the resulting product, concentrating
on the improvement and optimisation of physical processing and corresponding technologies. Nowadays,
they focus more and more on processing and data, since data analysis has
also become more and more important in this field. Furthermore, they
Oriane Guerin
with feed pellet
operate various individual projects to
samples
do with recycling food waste, such as
its conversion into bioplastics.
They also give independent adtein sources (other than “meat” from livevice to their clients about the use of
stock) is urgent. Marcel Dicke, Professor of
certain machines and the equipment needEntomology at Wageningen University and
ed in feed or food processing like mills and
Research Centre (WUR) is, together with
devices for coating and pelleting. For exhis colleagues Arnold van Huis and Henk
ample, milling processes are simulated in
van Gurp a great ambassador for eating inthe Zetadec lab before upscaling to indussects to overcome the world hunger. They
trial settings, requirements honed in close
even wrote a special insect cookbook with
cooperation with customers in their own
the subtitle “Food for a sustainable planet”
factories.
and promote insect food in several student
Will insects be the food of the future?
pubs in Wageningen and other Dutch cities
Last but not least, the Dutch scientists
by treating the guests to various little dishdeal with – yummy! – edible bugs.
es freshly prepared from insects.
That’s no joke. Edible insects
Roasted bugs and mealworm pizza
contain high quality proteins, vitaYour Lab Times reporter’s experience
mins and amino acids for humans.
of eating fried grasshoppers wrapped in
Insects have a high food conversion
Chinese spring rolls, roasted bugs, smoked
rate. So, for example, crickets need
salty ants and mealworms in pizza was not
six times less feed than cattle, four
that bad. The taste is comparable to eating
times less than sheep, and half as
conventional food like ham or shrimp and
much as pigs and broiler chickens to
not all disgusting, in fact surprisingly deliproduce the same amount of protein.
cious. Even Kofi Annan, the former SecreIn addition, they emit fewer greentary-General of the United Nations, is cithouse gases and less ammonia than
ed in Dicke’s book. He appraised crickets
conventional livestock. And, best of
and locusts as quite delicious, according to
all, insects can be grown on organic
the authors.
waste, according to the Food and AgThe FAO supports eating insects and has
riculture Organization of the United
worked since 2003 on topics pertaining to
Nations (FAO).
edible insects in many countries worldwide.
So insects are a promising source
As overall demand for food, particularly
for the conventional production (mimeat, increases due to population growth
ni-livestock) of protein, either for diworldwide, there is a need to increase the
rect human consumption, or indisupply of protein from sustainable sources.
rectly in recomposed foods (with exEdible insects have the potential to overtracted protein from insects); and as
come future shortcomings because most of
a protein source into feedstock mixthem, as we mentioned above, are protein
tures. The need for alternative pro-
page 46
03.09.15 12:47
Biobusiness
rich and can thus deliver a valuable contribution to a healthy diet. However, there
is a problem: In many countries, especially those in the West, eating insects is not
widely accepted.
Edible insects, funded by the EU
Research on edible insects is funded by
the EU with public money. Up until now,
however, little work has been done. Nobody
really wants to start using insects in food
and feed as a protein source because the legal framework is not yet resolved, according
to Zetadec’s Oriane Guerin. So she and her
colleague Yi are among the few doing pioneering work on edible insects.
Oriane Guerin, deputy CEO at the moment, has plenty of expertise. She holds
three diploma and/or master degrees, obtained in three countries; firstly a degree
in agriculture (Toulouse, France), secondly a degree in European animal management (Wales, UK and The Netherlands),
and thirdly a MSc in animal nutrition (The
Netherlands). Since 2010 she has been engaged as a researcher in feed technology at
Zetadec. Her colleague, Liya Yi, is working
on protein isolation and purification in insects as a postdoctoral project in collaboration with WUR, studying the characteristics of several insect proteins and how to
use them in food and feed.
5-2015
ed still to be investigated. The first question
to solve for Zetadec is, therefore: How can
we extract proteins from different insects?
Liya Yi recently wrote her PhD thesis about
this very topic. She and her co-workers at
Zetadec are currently performing pilot studies on the specific characteristics of certain
edible insects, including their protein content and nutritional impact. They are also
developing suitable diets for feeding different kinds of insects.
Still active at University
Thomas, our founder in a plastercast,
is also still active at Wageningen University, where he gives guest lectures to the
students about feed technology. He is part
of the “zzp-people-group”, which is a collaboration between several consultants
in the food and feed business arena. The
Dutch abbreviation “ZZP” means ‘zelfstan-
Lab Times
page 47
fast the company has grown in the last few
years: In 2011, there were only two people
doing the work, namely Menno Thomas and
Oriane Guerin, and in 2014 they were already a team of five.
Strong intention to stay independent
Zetadec wants to remain independent,
according to its founder, and is doing “correct” research (according to ethical guidelines and scientific truth). They are not
writing “biased reports”, Thomas affirms,
not even when certain clients would like
them to do so. In close cooperation with
their industrial clients they are working
on improving the actual customer product. They also have various cooperations
with the Dutch government and the European Union.
Thomas and Guerin prefer employees
who can “think outside of the box”, and an,
At Zetadec’s wet-lab
facilities for pilot
experiments, Oriane
Guerin is analysing the
latest data
Comparable to the ongoing discussion surrounding GMOs, it is still not clear
whether the harvesting of insect proteins
creates possible environmental or health
risks when used for human or animal consumption. Those issues have to be investigated before one can think of developing
technologies for processing insect material
in feed or food on an industrial level.
Another notable issue is whether people will consider the possibility of using
insect protein in their meals. Ethical considerations when killing insects also play a
role along with cultural barriers to do with
the fact that insects were raised on organic
waste and used as a source of nutrition later. The strict definition of feedstuff does not
seem to cover insects, “Animals (which are
classically used later for human consumption, e.g. poultry, cows, pigs) do not eat animal protein”.
Given the lack of a legal framework
these questions are yet to be answered.
Moreover, little to almost nothing is known
about the potential for allergies when eating insects. The possible side effects of insects used as feed or in food products need-
The risks are not yet clear
dig zonder personel’ and stands for small
start-ups which began as one-person companies. Within this network (and other similar relationships), they train together and
learn from one another.
Zetadec is also a member of Food Valley
NL, which boosts innovation performance
by fostering collaboration between businesses, knowledge institutions and government. Since the interest in insects as a protein source is growing, Zetadec is a founding father of the Insect Centre, a network
organisation working on the introduction
of insects in feed, food and pharmaceuticals products. Zetadec is also listed in the
“Edible Insects Stakeholder Directory” map
of the Food and Agriculture Organization
of the United Nations. It is remarkable how
“open and free working atmosphere”, too.
All colleagues, including the boss, regularly have lunch together. According to them,
it feels like a real “family company”. As it is
a typical part of Dutch work culture, they
have a team meeting at least once a week
where they report the progress of their projects and exchange news on internal and
external developments, activities with clients, and so on. Speaking different languages (Dutch, English, French and Chinese) is
no problem for them. Since they are a small
company, tasks are not strictly divided and
they are good at team work, they affirm.
Your Lab Times reporter didn’t ask them
the delicate question, however, of whether
they are obliged to participate in regular inInge Matthies
sect test meals.
03.09.15 12:47
page 48
Lab Times
Products
5-2015
Product survey: Cell culture media
No More Excuses
The cell culture community is shaken by scandals of adulterated and mislabelled fetal calf serum (FCS) almost
on a regular basis. At the same time, the number of serum-free media is steadily increasing. How many more FCS
frauds will it take, to stop the “FCS business as usual” attitude of many researchers?
FCS broker gang
That was basically the game plan of one
FCS broker gang operating in the nineties
from abattoirs in northern France, utilising
the French FCS supplier, Biowest, as a distribution platform for the adulterated FCS.
The illegal practices were uncovered when
LT_515_Product survey.indd 48
Photo: Jonathan Franks
I
t’s time to switch from cell culture media, supplemented with fetal calf serum (FCS) to serum-free, chemicallydefined media. That was the tenor of the
product survey “Cell Culture Media” in Lab
Times 4/2007 (page 53). Eight years later,
however, many life science researchers still
seem to be hanging on to their accustomed
use of FCS − despite sky rocketing FCS prices, repeated frauds of adulterated fetal calf
sera and a constantly growing list of chemically-defined media.
Prices for raw FCS derived from US cattle, which accounts for almost half of the
worldwide FCS supply of approximately
600.000 litres (from which only 200.000
litres are assumed to be suitable for GMP
manufacturing), exploded in the last years
to 700 dollars per litre. FCS from Australia and New Zealand, producing another
20 % of the worldwide FCS supply, is even
more expensive and sells well above 1.000
dollars. The major reason for the soaring
prices is a multi-year drought in the USA,
forcing ranchers in 2012 to dramatically
cut down their livestock roving around the
great western plains, leading to a severe
FCS shortage.
FCS extracted from South American cattle, however, is a bargain compared to FCS
from Oceania or the US: it goes over the
counter for around 100 dollars. This tenfold price span between the different origins is a perfect scenario for tricksters and
dubious FCS brokers. It’s fairly easy to imagine their business strategy: simply buy
cheap FCS from South American abattoirs,
adulterate and expand it with low-grade
sera or other obscure liquids and use false
certificates from European slaughterhouses
to sell the mixture as expensive, high quality FCS to clueless European customers.
Harvested whole blood with white blood cells, activated platelets and red blood cells. Platelet
lysate extracted from expired human platelet units may replace FCS in cell culture.
the Danish FCS producer, Sera Scandia, notified an ownership interest (i.e., purchasing considerable amounts of stocks or other
assets to control a company) in Biowest in
1994 and acquired the company completely
in 2004. Obviously, the Sera Scandia management had never heard of a due diligence
examination, which is a standard investment business procedure, to audit a potential investment. It took them ten years to notice that something was wrong with their
new daughter. Finally, the responsible manager was fired in 2004 and the case was put
forward to the French police for further investigations.
But as you might guess, that was not
the end of the FCS fraud story. According
to a Fetal Bovine Serum hand-out, available at the Biowest website (www.biowest.
net/download/fetal-bovine-serum-handout),
it was just the beginning. The French investigators more recently unravelled another
FCS broker gang in eastern France, which
had mislabelled and adulterated 110.000
litres of Brazilian FCS between 2004 and
2014, and had shipped 50.000 litres as CEmarked FCS to Germany.
Clueless customers?
Meanwhile, the Biowest managers have
taken the case to court in Baden-Baden,
Germany, blaming competing FCS suppliers for having sold adulterated FCS and violating ethical standards, by not informing
the clueless customers. The unappetising
details of this recent FCS scandal were also
reported in the German newspaper Die Süddeutsche and in the French gazette Le Courrier de l’Ouest.
But are FCS customers, i.e., life scientists, really that blank-faced, blissfully ignorant to what’s happening behind the FCS
scenes? Come on! Researchers are no dummies, so they should definitely know what’s
going on in the FCS business. And besides,
which reasonable researcher really wants
07.09.15 13:09
Products
5-2015
to depend on the weather conditions in the
USA and the number of livestock in Texas?
Let alone the ethical issues of FCS extraction and the not too unreal danger of FCS
contamination with exotic viruses, bacteria,
fungi or other obscure components.
So, the time has definitely come to
throw away outdated habits and switch to
serum-free, chemically-defined cell culture
media. Even more so, since the often heard
excuse that chemically-defined media supporting the growth of a specific cell line are
hard to find, is becoming more obsolete −
especially in stem cell research.
A recent review on the cultivation of human pluripotent stem cells, such as embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) in xeno-free culture systems, lists 14 different, commercially available, serum-free media for hESC and
hiPSC culture (Desai et al., Reprod. Biol. Endocrinol. 13, DOI 10.1186).
Some of them, like TeSR1 and E8, have
been on the market for almost ten years.
Others, such as StemFit, which has been
developed in the lab of stem cell pioneer
Joseph Itskovitz-Eldor at the Technion - Israel Institute of Technology in Haifa, are
brand new. All specified media are basical-
ly composed of a simple, but highly defined,
mixture of amino acids, vitamins, trace elements and growth factors.
The same holds true for the culture of
standard cells, such as CHO-cells, fibroblasts or cancer cell lines. You may find
commercial, serum-free media for maintaining the growth of almost every cell type.
And even better: the number of completely
chemically-defined media is also steadily
increasing.
Completely defined, allround media
Cancer researchers may, for example,
check out a new chemically-defined medium supporting the growth of different cancer cell lines. It has been elaborated by Rodney Nash and his co-workers at the Emory University School of Medicine, Atlanta,
USA. Nash seems very convinced about the
potential of his media formulation. He quit
his postdoc position shortly after his invention in 2014 and founded the company Jeevan Biosciences to commercialise the medium under the brand name NeuroPure.
According to a recent paper from Jeevan Biosciences, Nash’s chemically-defined
medium supports the growth of neuronal
cells, cancer cells and fibroblasts (Ann.
Lab Times
page 49
Transl. Med. (10):97. doi: 10.3978/j.issn).
His start-up company is currently investigating, whether it is also suitable for other
cell types such as iPSCs.
Human platelet lysate (hPL) extracted
from expired human platelet units is another promising alternative to FCS (though it
is not chemically-defined), which is especially useful for the expansion of mesenchymal stromal cells (MSCs). It is generated from platelet units by a simple freezethaw cycle process developed by Gerhard
Gstraunthaler’s group at the University of
Innsbruck, followed by centrifugation and
filtration to remove cell fragments (Cytotherapy, 16: 170-80).
Platelet lysate delivers a complex mixture of growth factors and is applicable
for different cell types, especially human
MSCs, endothelial cells and fibroblasts. It
is offered by specialised cell culture media companies and is also produced in
small quantities by laboratories related to
blood products or transfusion medicine,
such as the Centre for Clinical Transfusion
Medicine at the University of Tübingen,
Germany.
Harald Zähringer
Labvolution & Biotechnica 6/10–8/10 2015, Hannover, Germany
The new trade fair “Labvolution” provides
a platf
t orm for the entire world of lab
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equipment for the chemical and pharmaceutical industries, environmental technology and the food industry. More Information at www.labvo
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T o trade fairs.
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One admission ticket.
Crossover Visitor Traffic
The lab technology trade show “Biotechnica” – Europe’s No.1 event for Biotechnology, Life Sciences and Lab Te
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LT_515_Product survey.indd 49
Come and meet the Lab Ti
Tim
imes Te
T am at Stand
G74 in Hall 9. Yo
Y u will not only enjoy meeting
many interesting people, this is also your
opportunity to pick up a personal copy of the
latest Lab Times, along with a variety of
giveaways. Share your valued opinions with
our ever-zealous editors
r over a glass of sparkrs
ling wine or other refreshments. We look forward to welcoming you at “Labvolution”.
07.09.15 13:09
page 50
Lab Times
Products
5-2015
Cell Culture Media
Company/Distributor Name of product
Supported cells
Price [EUR]
AMS Biotechnology
Wide range of general and specific culture media including
Various cells
On request
BioCat
Adipocyte and preadipocyte basal, maintenance and differen-
Omental preadipocytes, omental adipocytes, subcutaneous
preadipocytes, subcutaneous adipocytes (human, mouse, rat)
Depending on
medium
All common cell lines
75.– (100 ml)
unique ranges of media for growth of stem cells
Abingdon, U.K.
www.amsbio.com
Contact: [email protected]
Phone +44 1235 828 200
tiation media
Heidelberg, Germany
www.biocat.com
DMEMgfp-2 Antibleaching Live Cell Visualization Medium
Contact: Elke Gamer
Phone +49-6221-7141516
[email protected]
Biomol
Great number of various cell culture media from US Bio and
Conda
Available for a comprehensive spectrum of diverse cell lines
Starting at 65.–
Biowest
Classical media such as: BME, CMRL 1066, DMEM, GMEM,
Ham’s F10, Ham’s F12 , Ham’s F14, IMDM, Leibovitz L-15,
McCoy’s 5A, Medium 199, MEM and RPMI 1640
Various cells
On request
LymphoGrow Medium
AmnioGrow Plus Medium
MarrowGrow Medium
Primary human blood lymphocytes
Primary human amnion and chorionic villi cells
Leukaemic bone marrow cells
On request
UltraCulture Serum-free Medium, General Purpose Medium
without L-Glutamine
Cultivation of adherent and non-adherent mammalian cells;
generation of viral particles for vaccine production
57.–
ProFreeze-CDM, NAO Freeze Medium
For cryopreserving many cell types in the absence of fetal bovine
serum (FBS)
88.–
X-VIVO Serum-free Hematopoietic Cell Media, chemically defined; X-VIVO10/15/20
For a variety of cells
From 46.–
Transfected and non-transfected CHO cell lines; HeLa cells;
human leukemia cell lines
From 58.–
Madin-Darby Canine Kidney (MDCK) and other kidney cells;
HEK 293 (adherent and suspension); Vero cells
From 36.20
Hamburg, Germany
www.biomol.de
Contact: Edgar Lipsius
Phone +4940 853260 37
[email protected]
Nuaillé, France
www.biowest.net
Contact:
Phone +33 241 464 242
[email protected]
Biozym Scientific
Hessisch Oldendorf,
Germany
www.biozym.com
Contact: Anja Roeben
Phone +49 5152 9020
[email protected]
Distributor of BioWhittaker CHO Expressionsmedia: UltraCHO Serum-free CHO cell
Medium; ProCHO Protein-free CHO Media;
Media from Lonza in
PowerCHO Serum-free CHO Media
Germany
Renale Media: UltraMDCK Serum-free Renal Cell Medium,
chemically defined; Pro293 Serum-free Media, chemically
defined; ProVero 1 Serum-free Medium
Insect-XPpress Protein-free Insect Cell Medium, with L-Glutamine For insect cell lines, e.g. Sf9 and Sf21
From 28.–
Hybridoma media: UltraDOMA Serum-free Hybridoma Medium; For cultivation of murine, human, and chimeric hybridomas
ProDoma Serum-free Hybridoma Media, chemically defined
From 25.–
Karyotyping Medium: Lymphochrome Medium
For the cultivation of lymphocytes from peripheral blood
From 31.–
Cytogenetic media: Amniochrome II Modified Medium;
Amniochrome Plus Medium; Amniochrome Pro Medium
For the culture of human amniotic fluid cells obtained from
amniocentesis
From 53.–
Dulbecco’s Modified Eagle’s Media (DMEM) in various variations Wide range of mammalian cell culture
From 6.30
DMEM:F12 medium in different variations
From 8.–
Used to demonstrate the effect of various hormones and growth
factors on target tissues | Clonal density cultures
Iscove’s Modified Dulbecco’s Medium (IMDM), various variations For fast growing cells | Formulas contain HEPES for added buffering From 8.30
Carl Roth
Minimum Essential Medium – Eagle (MEM Eagle / E-MEM) in
various variations
For a diverse spectrum of mammalian cell types
From 6.30
RPMI 1640 in various variations
Mammalian cells, especially hematopoietic cells
From 5.50
Insect media: Grace’s; Schneider’s; TC-100
Insect cell lines, organs for the propagation of entomopathic viruses From 13.40
Other classical media e.g.: Medium 199; Glasgow Minimum
Essential Medium (GMEM); Ham’s F10 and F12; L-15 (Leibovitz) Medium; McCoy’s 5A Medium
Wide range of mammalian cell culture applications
From 6.30
Roti-CELL DMEM High Glucose
Broad range of mammalian cell lines and primary cells
10.80 to 16.–
Mammalian adherent cell lines
10.80 to 13.50
Broad range of mammalian cell lines
13.–
Broad range of mammalian cell lines and primary cells
14.–
Roti-CELL Eagle’s MEM / Earle’s
Roti-CELL Eagle’s MEM / Hanks’
Broad range of mammalian cell lines and primary cells, including
transfected cells
10.80 to 12.50
13.50
Roti-CELL Eagle’s MEM-Alpha
Bone marrow cells, amniotic cells
12.20 to 23.50
Roti-CELL RPMI 1640
Suspension cell lines, primary B- and T-lymphocytes, leukocytes,
myeloma cells, hybridoma cells
10.80 to 43.80
Roti-CELL Ham’s F12
Various mammalian cell lines (particularly CHO), hybridoma cells
12.–
Roti-CELL Leibovitz’s L15
Various mammalian cell lines
19.–
Roti-CELL McCoy’s 5A
Primary cells and mammalian cell lines in general
18.–
Karlsruhe, Germany
Roti-CELL DMEM Low Glucose
www.carlroth.de
Roti-CELL DMEM:F12
Contact: Stefanie Seipp
Phone +49 721 5606 1038 Roti-CELL Iscove’s MDM
[email protected]
LT_515_50_54.indd 50
04.09.15 13:59
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LT_515_50_54.indd 51
04.09.15 13:59
page 52
Lab Times
Products
5-2015
Cell Culture Media
Supported cells
Price [EUR]
Carl Roth
Roti-CELL Medium 199/Earle’s
Fibroblasts and various cell lines
16.–
Contact: see page 52
Roti-CELL TC100 | Roti-CELL William’s E
Sf9 cells | Adult, primary hepatic epithelium cells
22.– | 18.–
Roti-CELL Hanks’ BSS |
Roti-CELL DPBS
Cells and cell lines in general
9.50 to 12.50
11.– to 18.–
CellGro DC (Serum-free)
On request
CellGenix PSC Kit
Generation of dendritic cells | Expansion of T-cells
Expansion of hematopoietic stem and NK cell culture | Generation of retroviral and lentiviral vector-producing cells
Multipotent stromal cells derived from umbilical cord matrix and
blood
Feeder-free expansion of human pluripotent stem cells (hPSC)
HyClone Media, HyCell CHO; HyCell TransFx-C
CHO lines
On request
CDM4CHO | SFM4CHO
CHO cell clones | CHO cells
On request
HyCell TransFx-H
HEK293 cell lines
On request
CDM4PerMAb
Production of human antibodies and recombinant proteins using
PER.C6 technology
On request
CDM4MAb; CDM4NS0; SFM4MAb
Hybridoma and myeloma
On request
SFM4Insect |
SFX-Insect
Many key insect cell lines, including Sf9, Sf21, etc. |
Insect cells
On request
SFM4MegaVir
Anchorage-dependent cell lines incl. Vero, MDCK, COS-7, MDBK cell On request
DMEM; MEM; RPMI; Ham’s; McCoy’s
Various cells
On request
HyCell STEM; AdvanceSTEM
Stem cells
On request
MEXi-CM Culture Medium
MEXi HEK293E cells (1,000 ml)
75.–
Goettingen, Germany
MEXi-TM Transfection Medium
www.iba-lifesciences.com
Contact: Ricarda Busse
Phone +49 551 506720
[email protected]
MEXi HEK293E cells (1,000 ml)
75.–
InSphero
3D InSight Tumor Microtissue Media kit
Tumor cell line-derived spheroids
346.–
3D InSight Human Liver Maintenance Medium
3D InSight Human liver microtissues (Incl. 3D Insight microtissues) 306.–
3D InSight Rat Liver Maintenance Medium
3D InSight Dog Liver/Minipig Liver/Cynomolgus Liver
Maintenance Medium
3D InSight rat liver microtissues
3D InSight dog liver/minipig liver/cynomolgus liver microtissues
297.–
306.–
3D InSight HepG2-Microtissue Maintenance Medium
3D InSight HepG2 liver microtissues
252.–
3D InSight Human Islet/Rat Islet Maintenance Medium
3D InSight human islet/rat islet microtissues
306.–
3D InSight Human Cardiac/Rat Cardiac/Human Brain Microtissue Maintenance Medium
3D InSight human cardiac microtissues/rat islet/human brain
microtissues
306.–
CellGenix
CellGro SCGM (Serum-free and Xeno-free)
Freiburg, Germany
www.cellgenix.com
Contact: [email protected] CellGro MSC (Serum-free)
Phone +49 761 888 890
GE Healthcare
LifeSciences
Little Chalfont, UK
www3.gehealthcare.com
IBA
Schlieren, Switzerland
www.insphero.com
Contact:
Phone +41 43 515 04 90
[email protected]
3D InSight Rat Brain Microtissue Maintenance Medium
3D InSight rat brain microtissues
306.–
Lonza Group
Classical media such as: DMEM, MEM, RPMI, IMDM and
insect media
Speciality media: CHO Expression Media; Cytogenetic Media;
General Use SF Media; Hematopoietic Media (X-VIVO); Hybridoma Media; Insect-XPress Protein-free Insect Cell Medium
with L-Glutamine; ProFreeze-CDM
Various cells
Please contact
your local
distributor
Merck-Millipore
Cellvento CHO chemically-defined cell culture media
Cellvento BHK cell culture media
Standard media
Customised cell culture media
CHO cells
BHK21 suspension cell lines
Various cells
On request
Miltenyi Biotec
StemMACS iPS–Brew XF, human (Xeno-free)
StemMACS Repro–Brew XF, human (Xeno-free)
Maintenance of human ES and iPS cells under feeder-free conditions On request
mRNA reprogramming of human fibroblasts into induced pluripotent
stem cells (iPS cells)
StemMACS HSC Expansion Media XF, human |
StemMACS HSC–CFU Media, human
Human hematopoietic stem and progenitor cells (HSPC)
On request
StemMACS MSC Expansion Media, human
StemMACS MSC Expansion Media XF, human (Xeno-free)
StemMACS AdipoDiff Media, StemMACS ChondroDiff Media,
StemMACS OsteoDiff Media, human
Human mesenchymal stem/stromal cells (MSCs)
MSCs
Generation of adipocytes/chondrocytes/osteoblasts from human
MSCs
On request
Mo–DC Differentiation Medium, human
On request
Mo–DC Maturation Medium, human
Differentiation of human monocytes into immature monocytederived dendritic cells (Mo-DCs)
Maturation of human monocyte-derived dendritic cells (Mo-DCs)
MACS Neuro Medium | DendriMACS GMP Medium
TexMACS Medium, research grade
TexMACS GMP Medium
CHOMACS CD | HybriMACS CD
Neural cells from human, mouse, or rat | Human dendritic cells
Human and mouse T cells and regulatory T cells
Human T cells and regulatory T cells
Chinese hamster ovary (CHO) cells | Hybridoma cells
On request
Neuron Growth Medium / Astrocyte Growth Medium
Neurons / Astrocytes
238.–
Mouse Embryonic Fibroblast Growth Medium
Mouse embryonic fibroblasts
219.–
Basel, Switzerland
www.lonza.com
Phone +41 61 316 81 11
Darmstadt, Germany
www.merckmillipore.com
Bergisch Gladbach,
Germany
www.miltenyibiotec.com
Contact: Jürgen Eiberger
Phone
+49 2204 8306 6641
juergen.eiberger@
miltenyibiotec.de
MoBiTec
Contact: see next page
LT_515_50_54.indd 52
04.09.15 13:59
Products
5-2015
Lab Times
page 53
Cell Culture Media
Supported cells
Price [EUR]
MoBiTec (continued)
Mesenchymal / Neural Stem Cell Growth Medium
Mesenchymal stem cells / Neural stem cells
238.–
Mouse Embryonic Stem Cell Growth Medium
Mouse embryonic stem cells
734.–
Adipose-Derived Stem Cell Growth Medium
Adipose-derived stem cells
255.–
Mesenchymal Stem Cell Adipogenic / Chondrogenic /
Osteogenic Differentiation Medium
Mesenchymal stem cells
298.– / 536.–
/ 206.–
Embryoid Body (EB) Formation Medium
Mouse embryonic stem cells
224.–
Cryopreservation Medium
Non Controlled-Rate Cryopreservation Media
Non Controlled-Rate Protein-Free Cryopreservation Media
Stem cells and primary cells (20 ml / 50 ml)
64.– / 129.–
83.– /153.–
89.– / 165.–
Pericyte Growth Medium / Pluripotent Stem Cell Medium
Human pericytes / Human pluripotent stem cells
182.– / 225.–
Keratinocyte Growth Medium Kit classic, low BPE / enhanced,
defined / enhanced
Human keratinocytes
122.– / 139.–
/ 133.–
Oral Epithelial Cell Growth Medium Kit enhanced, defined
Human oral epithelial cells
143.–
Airway Epithelial Cell Growth Medium Kit, defined /
Airway Epithelial Cell Differentiation Medium
Human airway epithelial cells
174.–
153.–
Mammary Epithelial Cell Growth Medium, defined
Human mammary epithelial cells
153.–
Corneal Epithelial Cell Growth Medium Kit enhanced, defined
Human cornea epithelial cells
164.–
Mesenchymal Stem Cell Adipogenic / Chondrogenic /
Osteogenic Differentiation Medium
Human mesenchymal stem cells
299.– / 549.–
/ 229.–
Smooth Muscle Cell Basal Medium classic
Human smooth muscle cells
85.–
Cellovations Endothelial / Cellovation Microvascular
Endothelial Cell Growth Medium Kit enhanced, defined
Human endothelial cells
229.– / 249.–
Fibroblast Growth Medium Kit defined
Human fibroblasts
229.–
Goettingen, Germany
www.mobitec.com
Contact: Arne Schulz
Phone +49 551 70722 0
[email protected]
Pelobiotech
Planegg, Germany
www.pelobiotech.com
Contact: Peter Frost
Phone +49 8951728659 0
[email protected]
PromoCell
Xeno-free Mesenchymal Stem Cell Medium Kit classic/Enhanced Human mesenchymal stem cells
179.– / 199.–
Supplement Kit for Cellovations Endothelial Cell Growth
Medium Kit defined
Human endothelial cells
179.–
Please find an extended list of media on our website
Various cells
Endothelial Cell Growth Media (4 media types)
Human endothelial cells from large vessels, human microvascular
endothelial cells
123.– to 137.–
Human vascular smooth muscle cells, human smooth muscle
cells from hollow organs
183.–
Normal human epidermal keratinocytes / melanocytes
107.–
162.– / 267.–
Fibroblasts Growth Media (3 media types)
Normal human fibroblasts from dermis, lung, aortic adventitial
tissue, heart ventricle, uterus
145.– to 149.–
Preadipocyte/Adipocyte Media (3 media types)
Human white preadipocytes (subcutaneous, visceral)
162.– to 228.–
Airway/Small Airway Epithelial Cell Growth Media (2 media
types)
209.– / 208.–
Primary human epithelial cells from nasal mucosa, trachea,
bronchium; primary human epithelial cells from bronchiole/alveoli
Mammary Epithelial Cell Growth Medium
Primary human mammary epithelial cells
111.–
Myocyte Growth Medium
Human cardiac myocytes
182.–
Skeletal Muscle Cell Media (2 media types)
Human skeletal muscle cells (myocytes)
163.– / 129.–
Various Growth Media for other types of primary cells
Human primary osteoblasts, chondrocytes, hepatocytes, renal ep- 131.– to 210.–
ithelial cells, placental epithelial cells, follicle dermal papilla cells
Heidelberg, Germany
www.promocell.com
Smooth Muscle Cell Growth Medium 2
Contact:
Phone: +49-6221-649340
Keratinocyte Growth Medium 2 / Melanocyte Growth Media
[email protected]
(serum-free or serum-free and PMA-free)
Sartorius
Goettingen, Germany
www.sartorius.com
Phone +49 551 3080
LT_515_50_54.indd 53
M1-/M2-Macrophage Media DXF | Dendritic Cell Media DXF,
Human mononuclear cells (freshly isolated), human monocytes
completely defined, xeno-free (w/o cytokines / with cytokines) (freshly isolated)
157.– / 579.–
157.– / 570.–
Dendritic Cell Media (w/o cytokines or with cytokines)
Human mononuclear cells (freshly isolated or cryopreserved),
human monocytes (freshly isolated or cryopreserved)
118.– / 284.–
Mesenchymal Stem Cell Growth Medium DXF, completely de- Human mesenchymal stem cells (from bone marrow, adipose
fined, xeno-free/Mesenchymal Stem Cell Growth Medium/Mes- tissue, umbilical cord matrix)
enchymal Stem Cell Differentiation Media (4 media types)
280.–
198.–
157.– to 367.–
Pericyte Growth Medium
Human pericytes
182.–
Hematopoietic Progenitor Expansion Medium DXF, completely
defined, xeno-free
Human hematopoietic progenitor cells, human CD133+ cells,
human CD34+ cells, human mononuclear cells from cord blood
184.–
Pluripotent Stem Cell Growth Medium DXF, completely defined, Human iPS cells, human embryonic stem cells
xeno-free
320.–
X-Vivo 20 w/ gentamycin and phenol red, 1 L
High-density LAK
92.–
X-Vivo 10 contains recombinant transferrin,
w/ L-glutamine, w/o gentamicin and phenol red, 1 L
X-Vivo 15 contains recombinant transferrin,
w/ L-glutamine, gentamicin and phenol red, 1 L
w/ L-glutamine, w/o gentamicin and phenol red, 1 L
Tumor-infiltrating LAK and lymphocytes
GLS Permexcis virus production med, 1 L
PER.C6 and related cell lines
129.–
111.–
138.–
73.–
04.09.15 13:59
page 54
Lab Times
Products
5-2015
Cell Culture Media
Supported cells
Sartorius
Insect-XPress w/ L-Glutamin, 1 L
Insect cell lines derived from Spodoptera frugiperda (Sf9 and Sf21) 47.–
Contact: see page 55
ProCHO5 w/o glucose, 1 L |
STD PowerCHO-2 CD, w/o L-Glutamin w/o PR, 1 L |
Mod PowerCHO1 w/ 3g/L Gluc & 4mM L-Glutamin, 1 L
CHO
60.–
69.–
69.–
ProMDCK (2D)/1 L | ProMDCK (3D), 1 L
MDCK
93.– / 81.–
ProNS0 1 CD | ProNS0 2 CD |
ProDoma 1 serum-free medium, 1 L |
ProDoma 3 wo L-Glutamin, phenol red w/ 0.1% Pluro F68, 1 L
CHO / Hybridomas
69.– | 69.–
65.– |
63.–
UltraCHO w/ L-Glutamin, 1 L
CHO
74.–
UltraCulture serum-free w/o L-Glutamin 500 ml
Adherent and non-adherent mammalian cells
59.–
UltraDoma serum-free w/o L-Glutamin 500 ml |
UltraDoma-PF Hybridoma Medium, 500 ml
Murine, human and chimeric hybridomas
26.–
ProPer-1 w/o L-Glutamin, phenol red w/ 0.1% Pluro F68, 1 L
PER.C6 and related cell lines
63.–
Classical Media: DMEM/F12 Media; Ham’s F-10 and
F-12 Media; Medium 199; MEM; RPMI 1640 Media; etc.
Various cells
On request
Serum-free media for different platforms, e.g., CHO,
Hybridoma, Insect and Vaccine
Various cells
On request
mTeSR1/TeSR2/TeSR-E8 |
Human embryonic stem cells and induced pluripotent stem cells
315.– /339.–/
208.– | 174.–/
181.–/203.–
Human embryonic stem cells and induced pluripotent stem cells,
Hematopoietic stem and progenitor cells
197.–
STEMdiff APEL/ STEMdiff APEL LI |
STEMdiff Neural Induction Medium
Human embryonic stem cells and induced pluripotent stem cells
133.–
199.–
STEMdiff Neural Progenitor Medium
Human ES/iPS-derived neural progenitor cells
299.–
STEMdiff Neuron Differentiation Kit / STEMdiff Neuron
Maturation Kit
Human ES/iPS-derived neural stem & progenitor cells, neurons
(available also for dopaminergic neurons, astrocytes)
From 149.–
STEMdiff Definitive Endoderm Kit
Human embryonic stem cells and induced pluripotent stem cells,
definitive endoderm
299.–
ImmunoCult Human CD3/CD28/CD2 T Cell Activator
Regulatory T cells, T cells
98.–
MesenCult
Mesenchymal stem cells
72.– to 558.–
MesenCult Osteogenic Stimulatory Kit (Mouse)
Mesenchymal stem cells, Mouse embryonic fibroblasts,
Osteoblasts (mouse)
423.–
StemSpan SFEM/StemSpan SFEM II |
Hematopoietic stem & progenitor cells
158.– to 530.–/
175.– to 592.–
186.– to 616.–
MyeloCult
Hematopoietic stem & progenitor cells (mouse or human),
stromal feeder layers
86.– to 305.–
MethoCult
Hematopoietic stem & progenitor cells
619.–
NeuroCult
Neural stem & progenitor cells (mouse, rat or human)
143.– to 261.–
NeuroCult SM1 Neuronal Culture Kit
Neurons
106.–
IntestiCult
Intestinal epithelial organoids
247
PneumaCult-Ex / PneumaCult-ALI
Bronchial epithelial cells
125.– to 185.–
Cellartis DEF-CS 500 Xeno-Free Culture Medium
GS1-R
GS2-M
Human iPS Cells
Rat embryonic stem (ES) and embryonic germ (EG) cells
Human and mouse embryonic stem (ES) and induced pluripotent
stem (iPS) cell lines
On request
Mouse embryonic stem (ES) cells
Human embryonic stem (ES) and induced pluripotent stem (iPS)
On request
NDiff 227
RHB Basal/RHB-A
Neural differentiation of mouse embryonic stem (ES) cells
Human and mouse neural stem (NS) cells
On request
Classical Gibco cell culture media
Mammalian cells
On request
Mammalian Classical Media; Mammalian Protein Expression
Media; Hybridoma Media; Primary Cell Media; Stem Cell
Media; Neurobiology Media; Insect Media; Microbiology
Media; GlutaMAX Media; Reduced-serum Media
Various cell types
On request
Serum-free media for example: CHO Cell Culture Media;
Various cell types
PER.C6 and 293 Media; Insect Cell Media; Immunology Media,
Stem Cell Media; Hybridoma Media; Primary Cell Media
On request
CHO Medium | CHO Feed – customised formulation
On request
Sigma-Aldrich
St. Louis (MO), USA
www.sigmaaldrich.com
Stemcell Technologies
TeSR-E5/TeSR-E6/TeSR-E7
Cologne, Germany
www.stemcell.com
Contact:
Repro-TeSR
Phone +49 221 888 7990
[email protected]
StemSpan-ACF
Takara Clontech
www.takara-bio.eu
Contact: orders@
clontech-europe.com
[email protected] iSTEM
Phone +33 1 3904 6880 PrimeSTEM-XF
Thermo Fisher
Scientific
Waltham (MA), USA
www.thermoscientific.com
Xell
K1, GS, DHFR-, DG44
HEK Medium | HEK Feed – customised formulation
HEK and other human cell lines
Bielefeld, Germany
Contact: Tim Beckmann
Hybridoma Medium | Hybridoma Feed – customised formulation Hybridoma cell lines
Phone +49 521 96989200
Customised media products for other cell lines
BHK, Vero, MDBK, MDCK, etc.
[email protected]
LT_515_50_54.indd 54
Price [EUR]
On request
On request
04.09.15 13:59
Methods
5-2015
Lab Times
page 55
Tips and tricks of the trade
Quick, Easy and Cheap
Protein Visualization
Tryptophans are not the most abundant of protein residues. But you don’t need a lot of tryptophans for staining
proteins in polyacrylamide gels.
Lab Hin t
CBB
Ferricyanide
N
Oxidising tryptophans
My group at the Department of Life Sciences, Institute for Multidisciplinary Research, University of Belgrade, looked for
a new way to employ proteins’ constituent
fluorophores in visualization and came up
with a method that relies on the oxidation
of tryptophan (Trp) residues (Pristov et al.,
Anal. Biochem. 480, 6-10). We tested several oxidising agents and tuned the method
using different concentrations, incubation
times, and pH values.
The best performance was obtained for
the following protocol:
Place gel in water solution of
K3[Fe(CN)6] (100 mM) and NaOH (1 M).
Incubate it in the dark at room temperature for 30 min.
Transfer the gel to water (no washing is
needed) and voilà, it is ready for scanning.
Potassium
ferricyanide
(III) oxidises
Trp at 25 °C
and high pH.
LT_515_Tips and Tricks.indd 55
Killing two birds with one stone
Photo: Ivan Spasojevic
ative and sodium dodecyl sulfate
(SDS) polyacrylamide gel electrophoresis (PAGE) is one of the most
frequently applied techniques in life science
labs. Following PAGE, protein bands are
commonly visualized using the Coomassie
Brilliant Blue (CBB) protocol, silver staining, or different fluorescent stains.
Each of these staining procedures, however, fails to meet at least one of the dream
features from the title: CBB is not quick (although the overnight staining is rather popular), silver is everything but easy (e.g. very
sensitive) and well-performing fluorescent
stains are not cheap, at all. So, novel approaches for in-gel protein visualization are
more than welcomed.
serum albumin (3 Trp per chain) as a standard, the sensitivity was comparable to CBB
and about 3.5 times lower compared to the
optimal settings. In other words, under optimal scanning settings, the sensitivity of
ferricyanide staining equals the sensitivity of CBB multiplied by the number of Trp
per chain. For example, if you invest a lot
of time isolating some protein that is luckily Trp-rich, the application of ferricyanide
staining can save much of your precious
sample.
Native PAGE gel of human plasma (5 µL per
lane) stained with ferricyanide or CBB.
Potassium ferricyanide is light-sensitive, so the solution should be freshly prepared for staining and kept in the dark. It is
also important to have in mind that a high
concentration of NaOH provokes protein
denaturation (in order to bring “buried”
Trp residues to the surface). A short exposure of stained gels to light as well as repetitive scanning, do not have negative effects
on sensitivity.
No special equipment needed
Fluorophore that is produced via
ferricyanide-provoked Trp oxidation shows
maximal excitation/emission at 345/460
nm. At the moment, this would require
non-standard equipment.
Fortunately, the fluorophore can be excited with wavelengths between 300 to 450
nm, with emission in the 420 to 550 nm
range; these settings are met by a number
of commercial gel scanners. With excitation/emission at 395/525 nm and bovine
Band fluorescence intensity is directly
proportional to the number of Trp in the
band. And here lays yet another advantage
with this method: it can be useful in Trp
quantification. Calibration fit for band fluorescence intensity and the number of Trp
(nmol) per band is created using equimolar
(subunit) amounts of a set of proteins with
different number of Trp per chain/subunit.
Another calibration fit is prepared for band
intensity and the amount of proteins (µg)
using CBB staining.
With these two, the amount of Trp per
µg of protein can be calculated for experimental gels. This might be useful in the
process of identifying proteins in biological samples, by narrowing down the list of
‘‘suspects’’ according to the number of Tryptophans.
Erase instructions
Of note: if, at some point, you are not
satisfied with the results of this staining
protocol, the gel can undergo post-staining
with CBB without any loss of sensitivity.
Ivan Spasojevic
Do you have any useful tips?
Contact
at: tips?
Do you have
anyususeful
Contact us at:
[email protected]
[email protected]
07.09.15 13:10
page 56
Lab Times
Methods
5-2015
Bench philosophy (58): Isothermal DNA Amplification
PCR's Smart Isothermal Cousins
W
Temperature issues of PCR
So thank you, Taq, and your small band
of similar, tough-skinned polymerases. You
have solved the heat problem. Well, sort of.
The temperature issue rules PCR out for a
lot of applications. First of all, forget about
applying PCR to living tissues. And that's a
LT_515_Bench Philosophy.indd 56
Handheld "Paper machine" for easy molecular diagnostics in four steps, applying loopmediated DNA amplification.
big loss, considering the huge interest in
detecting DNA or RNA sequences in living
cells. Take microRNAs for example. Given
our comparative ignorance of the biological
roles of miRNAs and their possible roles in
disease, it is vital we find ways of accurately measuring what miRNAs are being expressed in tissues.
So wouldn't it be nice to be able to do
the whole thing at the same temperature?
That would make the amplification much
more efficient and save a bit of time – after
all, amplification only takes place at one
part of a PCR thermocycle. And while we're
at it, another real plus would be if that temperature happened to be one that doesn't
cook tissues. Can this be done? Yes it can –
indeed, isothermal amplification is a fastmoving and exciting field that has been
somewhat eclipsed by PCR and its variants.
Byzantine in complexity
Isothermal amplification refers to amplification methods that take place at a
constant temperature. The lack of cycling
means that all the time is being spent on
amplification, not just part of a cycle. And
it means cheaper equipment, such as a water bath – good news for the lab budget.
On top of all that, isothermal strategies are
often more sensitive and more specific. So
what isothermal amplification strategies
are available? How good are they and do
they compare well against good ol' PCR?
Furthermore, who is using it and for what?
The answer to the first question is simple – there is a whole host of them. Their
sheer variety defies any attempt to classify
them. Often almost byzantine in complexity, they are an illustration of the ingenuity of their developers and show what can
be done with some imaginative cobbling
together of different molecular tricks and
tools. And yet, there is just one thing they
all have in common – they all incorporate
a trick to get the newly-synthesised DNA
strand to move off out of the way and allow
further rounds of extension to take place.
Different approaches
So how do they do this? Take a method called Strand Displacement Amplification (SDA) as an example. This uses a
primer against your DNA target that also
includes a HincII recognition site. You let
the DNA polymerase do its work and extend the target but you include in your mix
some deoxyadenosine 5'-[α-thio]triphosphate (dATP[αS]). The new strand incorporates the HincII site but the HincII can't
nick the dATP[αS]. The result is that the
primer, and not the target, gets nicked. This
leaves a 3' hydroxyl end, which gets extended by the DNA polymerase, displacing the
original primer. And so the cycle continues.
Clever.
And that was just plain vanilla SDA.
There are also some new, more elaborate
here would we be without PCR?
Whenever you find yourself
wanting to amplify up a bit of
DNA, that famous TLA (three-letter acronym) springs to mind in a flash. It stands
for Polymerase Chain Reaction, by the way,
and it is the cornerstone of molecular biology, allowing tiny amounts of DNA to be
amplified.
And as with PCR, so with many other
tools in our molecular toolbox: it all comes
down to a gift of Nature. All the clever stuff
in PCR is done by the DNA polymerase enzyme, which grabs nucleotides kindly chaperoned by the transfer RNA and attaches
them to a template strand. The in-built complementarity of Nature's four nucleotides
ensures (at least with reasonable fidelity)
that the new strand is a fair copy of the original – only in mirror image, so to speak. This
strict complementarity means PCR is sensitive and specific. The biology takes care of
it all.
But much as we love it, PCR has its limitations and one of those is the awkward regime of temperature cycles it needs to get it
to work. Indeed you need to get up to some
sweltering temperatures, all because, once
the polymerase has done its job, you have
to pull the complementary strands off the
target. In the lab this is done by heating the
DNA up: when things get hot, the two DNA
strands part company as the DNA simply
melts apart.
The problem is, this happens at about
70 °C, which is more than warm enough to
cook most enzymes (just try putting your
finger in water that hot), including the polymerase enzyme. However, rescue came
from a thermophile bacterium, which kindly gave us a super, heat-resistant polymerase called Taq, which made PCR easy and
Cetis Corporation very rich.
Foto: American Chemical Society
Most researchers associate DNA amplification with PCR. Nucleic acids may also be amplified isothermically,
avoiding PCR's time-consuming temperature cycles and sloppy specificity.
07.09.15 13:11
Methods
variants on the block, including "SDA-Ligase-G-quadruplex peroxidase detection"
strategy. This is so specific that it has been
used to detect variations of a single nucleotide with incredible sensitivity. How does
it do this? To start with, three probes are
used. Two of them are specific to either
wild-type or mutant (called the discriminating probes) and a third can bind to either.
If the discriminating probe binds perfectly with the target, it ligates with the third
probe and rounds of SDA can proceed. If it
doesn't match perfectly (because of a polymorphism or mutation), ligation doesn't occur and neither does SDA.
Superior specificity
This approach has been used to identify specific miRNAs in single cells and in
breast cancer patients – RuiXue Duan and
colleagues at the Huazhong University of
Science and Technology, China, could detect just nine strands of miRNA in a 15 µL
sample (Duan et al., 2013, J. Am. Chem.
Soc.).
Another isothermal method is best
suited for detecting RNA and it is called
Nucleic Acid Sequence-Based Amplification (NASBA). This starts with a primer
(RNA+) that is complementary to the target RNA(+) but also contains a T7 promoter sequence. The primer directs synthesis
of a single strand of DNA(-), resulting in a
DNA-/RNA+ hybrid. Meanwhile, RNAse H
digests the original RNA+ primer, leaving
the single-stranded DNA exposed as a template for reverse transcriptase generation of
double-stranded DNA.
This dsDNA is the entry point for the
amplification cycle, as its T7 promoter sequence (it was in the original primer, remember?) directs the synthesis of lots of
new RNA(-) molecules. These, in turn,
are bound by a reverse primer and, once
again, the DNA+/RNA- hybrid is produced,
which, when RNAse H has digested the
RNA(-) strand, leaves another single stranded DNA(+). Just like before, this is turned
into dsDNA, which directs the synthesis of
RNA(-), and so the cycle goes on generating RNA(-) exponentially.
Smart amplification strategy
SMART – Signal Mediated Amplification of RNA Technology (see what they did
there?) – uses a three-way junctional complex. The idea is to have two primers that
bind flanking regions of the target DNA.
Only when the two primers bind do they
form a stable bond with each other. One of
the primers is longer than the other, and
LT_515_Bench Philosophy.indd 57
5-2015
contains a T7 promoter and a transcription
template (used for recognising the RNA).
Once the three-way junctional structure has
thus formed, the longer primer directs elongation of the shorter one. The T7 promoter drives RNA synthesis from the resulting
dsDNA, resulting in many copies of RNA,
which can be detected by many different
possible methods.
Loop-mediated amplification
One of the most popular isothermal amplification strategies is called LAMP, which
stands for Loop-Mediated Amplification.
LAMP works using two pairs of primers
(two forward and two backward primers).
Each pair consists of an inner primer and
an outer primer. The inner primer also contains a sequence (F1c) complementary to a
region (F1) slightly further along the target
sequence. As this strand gets synthesised
(we'll call this strand S1) it picks up a second F1c from the F1 on the target sequence.
Meanwhile, the outer primer starts extending, pushing S1 off, while the F1c originally
present in the primer, folds over and binds
to the new F1c. This gives a dumbbell shape
at the 5'-end.
The same happens at the 3'-end thanks
to the work of the backward pair of primers.
Result: a double dumbbell structure looking
a bit like a closed staple. A bit more work
by the DNA polymerase turns the dumbbell into a stem loop structure and this
stem loop undergoes a proliferative recycling phase. If all that was just too much to
follow, the Eiken Chemical company has a
pretty animation to show the whole process
(http://loopamp.eiken.co.jp/e/lamp/anim.
html).
Faster and cheaper
So how does LAMP compare with its
older cousin, PCR? First of all, it is faster
and cheaper. It is faster because there is no
thermocycle involved and cheaper for the
very same reason. But many labs have also
found it to be more robust and more sensitive than PCR, and this is credited to the fact
that it recognises no less than six separate
sequences in the target. In the original paper, in which LAMP was announced, its inventors showed evidence that LAMP amplified just six copies of target molecule (Notomi et al. 2010, Nucleic Acids Research).
LAMP is also claimed to have higher
specificity than PCR. Indeed, one of the
problems with PCR is it is often thrown off
the scent by irrelevant DNA present in a
sample. Again, in the original paper, just six
pieces of target were successfully amplified
Lab Times
page 57
up, despite the contaminating presence of
100 ng of human DNA in the LAMP reaction
mixture. This robustness against interfering
materials makes LAMP particularly appealing in clinical diagnostic applications. And
as far as simplicity goes, all you need to do
LAMP is have the four primers, DNA polymerase and a laboratory water bath.
No wonder then that LAMP has established itself as a standard tool for molecular diagnostics in the field, such as identifying species. Most often, it has been used
for identifying pathogens, either in the field
or in biological samples. LAMP has been
shown to be successful in signalling the
presence of Neisseria meningitidis, the bacterium that causes meningitis and other serious illnesses, in cerebrospinal fluid (Lee et
al., 2015, PLoS ONE).
Paper-based DNA amplification
But the prize for the most amazing application of LAMP must surely go to George
Whitesides and his group at Harvard. In a
recent issue of Analytical Chemistry, Whitesides announced a hand-held, paper-based
(yes, you read that right – paper based!) isothermal DNA amplification device that can
detect E. coli bacteria in a sample, and all it
needs is a UV source and a camera phone
(Connelly et al., Anal. Chem., 87, 7595-601).
It uses paper microfluidics and a multilayer gadget that allows you to add the
sample, push in a slider, and then add buffer and LAMP master mix again just by pushing in another slider. After an hour's incubation at 65 °C, you add a bit of SYBR Green,
shine your UV onto it and take a snap with
your camera phone. And with as few as five
E. coli in the sample, it glows bright green
to give a positive signal.
Isothermal DNA amplification is not
new but it seems to be going through its
own proliferative amplification stage, as
researchers are finding more and more
novel applications, especially in contexts
where either low temperatures are required
(such as in vivo applications) or where economic (when you can't afford a thermocycler) or strategic (developing hand-held,
in-field devices) considerations are important.
Steven D. Buckingham
Fancycomposinganinstallmentof“BenchPhilosophy”?
ContactLabTimes
E-mail:[email protected]
07.09.15 13:11
page 58
Lab Times
Products
5-2015
New Products
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Advantages: The system provides accurate
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More Information:
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Photometry
Product: Screw caps for storage tubes
Name & Manufacturer: Low profile screw
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Technology: The low profile screw caps are
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Histopathology
Product: Spectrofluorophotometer
Name & Manufacturer:
RF-6000 from Shimadzu
Technology: The instrument offers the highest
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LT_515_New Products.indd 58
Product: Modular embedding system
Name & Manufacturer: HistoCore Arcadia
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Technology: The embedding system is a
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Advantages: The kits are intended to be typically used in solid organ or bone marrow transplant recipients to measure alterations in immunosuppression.
More Information: www.Lophius.com
07.09.15 13:11
Book Review
5-2015
Lab Times
page 59
Books on evolution for pre-schoolers
Apes Don’t
Celebrate Birthdays!
It may be that “The first book on evolution for pre-schoolers”, reviewed here,
isn’t the very first at all. Your Lab Times reviewer was nevertheless full of praise.
I
n recent years, I have written several
reviews of children’s books about evolution for my German blog (http://
wissenskueche.de). All of the books were
for school children aged eight and above
and I tried to find books for smaller children
without success. This was surprising, given
that, in my experience, even four-year-olds
show a strong interest in dinosaurs and fossils, which is a great start for first steps to
scientific literacy in evolution.
I found out that pre-schoolers can
grasp the basics of evolutionary biology when the kindergarten teachers of my
child invited me to talk at a science project last year. Knowing that I am a biologist, I was asked to answer the kids’ questions, including “What were the first animals on Earth?” and “When did the first humans live?” The kids and I enjoyed a lively
chat about how we scientists know about
things that happened long ago and why we
think the ancestors of all the animals and
plants changed over time. They knew a lot
already, not only about dinosaurs, but on
similarities and differences between humans and their nearest relatives, too. I was
amazed by statements like “Apes don’t celebrate their birthdays”.
After this experience, I knew for sure
that there is no good reason for the lack of
books on evolution for young children.
Crowd-funded project
So, I was excited when I discovered the
crowd-funded book project Grandmother
Fish, by Jonathan Tweet, a US designer of
tabletop, role-playing games, who applied
his storytelling talents to create a book that
he, as an atheist and father, had found was
missing. His idea and text came to life with
the help of drawings by Karen Lewis, an
experienced illustrator of science for children.
To make the book accessible for the
very young, it is conceptualised as being
read interactively, coaxing the children to
wiggle and chomp like grandmother fish,
LT_515 Books.indd 59
crawl and breathe like grandmother reptile,
squeak and cuddle like grandmother mammal, grab and hoot like grandmother ape,
and walk and talk like grandmother human.
With its engaging texts and charming
drawings of animals and their evolutionary
family tree, the book manages to get basic
concepts across in a very child-friendly way
– of a common origin of all life, and of ancestral and derived traits of the organisms living on earth right now. As Jonathan Tweet
told a US newspaper, “It’s a very simple story but a lot of thought has gone into it.”
Natural selection explained simply
In the last section of the book, the author added information for grown-ups and
older children to tackle some misunderstandings about evolution people tend to
have. Here, names, facts and dates are given, and natural selection is explained in
admirably simple terms; even more importantly, in words avoiding the line of
thought associating nature with “red in
tooth and claw”.
To me, this is a clear sign that Jona
than Tweet is aware of the fact that the
religious conservatives aren’t the only influence which might let us shy away from
talking about evolution with our kids. For
many church-critical progressives the stories about evolution have a bad taste, too, as
far-right ideology has often used biologistic
evolutionary explanations to fight against
an open, egalitarian society.
In my view, Grandmother Fish isn’t primarily written as a challenge to the belief of
God creating earth and life on it. It is rather written for the liberal science-loving parent or teacher, who accepts evolution but
has trouble with the bad vibrations that result from the twisted and malicious use of
evolutionary thinking in social Darwinism.
Jonathan Tweet does a great job in avoiding
the pitfalls of inept associations that might
reduce the enthusiasm of people when talking with their children and pupils about our
evolutionary ancestry.
In his book, the idea of the survival of
the fittest isn’t a tale about killing and being
killed, it is one about safety. The pictures
show animals and humans enjoying their
lives, caring and being social. And in the
science notes at the end of the book Tweet
writes, “Baby animals are born with differences, and some differences make them safer. Animals that keep themselves safer have
more babies.”
A tale of belonging together
The book surely is about basic science
facts, but it also wants to tell a humanist’s
tale of interconnection and of belonging together. When it comes to Homo sapiens it
says, “We are all closely related, and we are
one human race.”
Grandmother Fish is at the printer right
now with its Kickstarter investors waiting
to get their copy of the 32-page hard cover
book. Pre-orderers can join them for $20.
Unfortunately, the shipping fee outside of
the US is quite high ($30). But according
to the author, the book will be available
on Amazon, too. In the meantime, you can
check out the PDF of a draft version (to be
downloaded at www.grandmotherfish.com/
grandmotherfish.pdf) – or you can while
away your children’s time with an equally
recommendable alternative that your Lab
Times reviewer finally picked out, when
investigating for this review: Neal Layton’s The Story of Everything (published in
2006).
Brynja Adam-Radmanic
u Grandmother Fish. A child’s first book of
evolution. By Jonathan Tweet & Karen Lewis (Illustrator). 2015, Hardcover, $20 (plus
shipping fees to Europe: $30). ISBN13
9780986288401. More at www.grandmotherfish.com.
u The Story of Everything. A pop-up book
with pops, flaps and tabs. By Neal Layton.
Hodder Children’s, 2006. 30 pages, 3 to 6
years, €14.
02.09.15 21:57
o:
ot
Ph
Lab Times
Careers
5-2015
ki
be
em
/
lia
to
Fo
page 60
Career strategies for young European scientists (LVI)
“I’m Interested in Different
Types of Questions about Science”
For our irregular series “Alternative Careers in Science”, we talked to Emma Frow, who at some point realised cell
biological research couldn’t excite her anymore. That’s when her career path took a detour.
E
mma Frow is an assistant professor at
Arizona State University. She start
ed her career with studying Natu
ral Sciences and doing a PhD in cell biolo
gy at Cambridge
University. She
left the lab to
work as a sub
editor for Nature
in London, and
then turned to
social sciences,
gaining an MSc
in Science and
Technology Studies from the University of
Edinburgh. We spoke with her about a life
between science and society.
Lab Times: Emma Frow, obviously two
souls are dwelling in your chest. Why did you
study biology and even do a PhD, but then
turn to social sciences?
Frow: Actually, I almost didn’t take biol
ogy at High School in Canada. But my mum
suggested that it was probably a good idea
that I take it. When leaving school, I wasn’t
sure whether to study languages or science.
In the North American university system
you can combine arts and sciences, but this
isn’t typical in the UK, where I went to uni
versity. In the end, I decided that I would
rather keep languages as a hobby and it felt
a bit harder to do science as a hobby. So I de
cided to study science as an undergraduate.
LT: You continued doing science. How did
you pick cell biology as your favourite?
Frow: One day in college, I walked by
a notice advertising summer student posi
tions in a lab in the Department of Med
icine. I thought it looked interesting and
hadn’t yet made summer plans. So I started
working in this lab and I really enjoyed it. I
had a great summer and I even managed to
publish a journal article from the research.
I realised I had quite green thumbs when it
came to lab work. At the end of the summer,
LT_515_60_61.indd 60
my supervisor invited me back to do a PhD.
It wasn’t something I had planned to do but
I enjoyed the lab work, the people and the
atmosphere in the lab, so I ended up stay
ing there for my PhD.
to discussions with colleagues and friends
about how science is funded, about the re
producibility of experiments, and so on. In
my free time, I would go to talks and lec
tures by people who were communicating
about science and the relationship between
science and society, and in the final year of
my PhD, I started volunteering for a science
policy initiative based in London.
LT: And what prompted you to move away
from the lab?
Frow: Well, by the end of my PhD, the
questions that I found most interesting were
not ones that could be answered by doing
LT: How did you move into the field called
scientific experiments. I was doing eight to
social studies of science?
ten hours a day of cell culture, repeating
Frow: It took me a while to discover the
experiments under various conditions but
field of science studies but once I found it,
I was starting to question whether the work
I knew it was what I had been looking for.
was biologically relevant, whether it would
As a scientist, the options that seemed most
make any difference. I found myself in a sit
visible to me when I was thinking about
uation where the questions that excited me
moving away from the lab bench included
most were not “does that protein interact
science communication, history and philos
with this protein under these conditions?”,
ophy of science, and bioethics. I wasn’t sure
which is what some of my friends went to
that any of these offered quite what I want
bed dreaming about. In Cambridge, people
ed. Science and technology studies is an
are often completely ab
interdisciplinary field that
sorbed by their work and “I was starting to question
distinguishes itself from
whether my work would
I wasn’t sure that I want
philosophy of science and
make any difference.”
ed to enter into competi
bioethics by being explic
tion with my fellow PhD
itly concerned with prac
students for the next round of postdoc and
tice, with looking at what scientists do, how
faculty positions; I just didn’t feel commit
they do it and why they do it, and what this
ted enough to laboratory work.
means for the knowledge that is created and
its relationship with society.
LT: Did you think you were a bad or, at
How did I move into this field? It has
least, not a really enthusiastic scientist?
happened gradually. I started retraining
Frow: No, I don’t think I ever felt like
when I moved up to Edinburgh in 2006,
I was being a bad scientist. I think, often,
to take up a postdoc in a unit called the
people assume that if you leave the lab, you
Genomics Policy & Research Forum. I have
are not a good scientist. Well they can think
gotten several jobs thanks to friends and
what they want (laughs). That doesn’t re
colleagues, who have spotted positions they
ally bother me. I’m still very interested in
thought sounded like me: I was working at
science but I’m just interested in different
Nature when a friend sent me a notice for
types of questions about science.
the postdoc position in Edinburgh. A similar
thing happened with my current position
LT: So what were you dreaming of if it
at Arizona State University. You could say
wasn’t your next experiment?
that my jobs have tended to find me. Sor
Frow: It took me quite a while to refine
ry for not being straight forward (laughs).
the questions that I’m really interested in.
You said you were interested in quirky ca
When doing my PhD, I found myself drawn
reer paths!
03/09/2015 14:44
Careers
5-2015
Lab Times
page 61
Careers in academia
LT: So you got your first position in soFrow: It’s a tricky problem. I think you
edge from biology are coming together in
cial sciences without any training in social
have to start with an understanding of what
synthetic biology. There are some very in
sciences?
scientists’ working lives are like – what con
teresting similarities and differences be
Frow: Not exactly, I would never have
straints they face, what issues they encoun
tween how engineers and biologists ask
gotten a postdoc position as a social scien
ter, and what kinds of questions might be
questions and develop projects.
tist without any training. But I was lucky
relevant and interesting to them. You can’t
that the Genomics Forum was a unique
force scientists to engage with broader
LT: Are there clear differences between
place. It was designed as a kind of institute
questions but in practice most scientists
biologists and engineers?
or space that was charged with designing
have their own experiences of them, even if
Frow: Well, they certainly present
activities to bring together all types of stake
they’re in quite practical settings – for exam
themselves as having different approach
holders with an interest in genomics and
ple, you should have some understanding
es to the world! Often, in synthetic biol
the life sciences, includ
of the broader con
ogy we hear caricatures that biologists
“One approach is to make ening social scientists, bio
text of your work to
are more interested in understanding the
logists, physicians, mem gagement with the social dimenwrite a grant propos
world, while engineers are more interested
bers of the public, policy
al that will be persua
in building with biology. This does shape
sions of science compulsory.”
makers, industry, and so
sive to your funder. I
the kinds of questions that researchers from
on. To help do this, the Genomics Forum
often start informally by just seeing who
different disciplines ask and the ways that
hired postdocs with training in quite differ
shows interest, finding out what interests
they organise their practices in the labo
ent fields. When I started, there were seven
them and then developing discussions from
ratory. There are also differences in how
of us with very different backgrounds: eco
there. I’ve been at ASU now for six months
engineers and biologists are trained as un
nomics, theology, microbiology, psycholo
and I have had three or four engineering
dergraduates, with engineers typically fol
gy, law, ethics and me. We were charged
students, who have approached me saying
lowing more structured and rigid curricu
with identifying themes and developing ac
they are interested in policy aspects of their
la than biologists. Engineering is a profes
tivities to foster interdisciplinary dialogue.
research. I’m starting with them and let’s
sional degree but you don’t need the same
It was through this work that I really started
see where we end up!
kind of formal certification to practice as a
engaging with social scientists: asking them
Another approach is to make engage
biologist.
about their research and asking them to ex
ment with the social dimensions of science
plain to me why it mattered. After a couple
compulsory. To give you an example from
LT: What other issues are you interested
of years, I was convinced that the sorts of
Edinburgh: about five years ago, the uni
in, what would you like to study?
questions that researchers in science and
versity was setting up a new Masters pro
Frow: Right now I have several syn
technology studies were asking, were things
gramme in Systems and Synthetic Biolo
thetic biology projects underway; there’s a
I was interested in exploring myself.
gy and was looking for faculty to propose
great appetite among biological engineers
new courses. A colleague had been studying
for social scientists to be involved in the de
LT: What is your current job at the Arizothese fields for a while and decided to pro
velopment of this field. I’m still very inter
na State University?
pose a social science course on Systems and
ested in image production and also in the
Frow: Again, it’s an unusual job. I have
Synthetic Biology for
role that journals play
“There’s a great appetite among
a split position, with 50% based in the
the students. It must
in the production of
School of Biological and Health Systems En
have been a timely biological engineers for social sciscientific knowledge.
gineering, and 50% in the Consortium for
proposal because our entists to be involved in the develI’m not aware of any
Science, Policy & Outcomes, which is one
course ended up be
anthropological stud
opment of synthetic biology.”
of the larger departments in the US with
ing one of three com
ies of how journals
a focus on science policy and science stud
pulsory courses in the degree programme.
operate, I think that would be really inter
ies. My office space and my ‘lab space’ are
So, any student who takes that masters in
esting and fun to do.
based in Engineering, and I have a remit to
Edinburgh has to spend 30 hours with us
help embed policy and society considera
– lucky them! We approach the course by
LT: Don’t you miss the wet lab?
tions into the engineering teaching curric
identifying issues that scientists in the field
Frow: (laughs): You know, I have found
ulum, and to encourage the growth of re
are talking about (e.g. in journal editorials
a substitute for lab work: cooking! It’s not
search collaborations between engineers
and commentaries) and then providing a
ambitious nouvelle cuisine but I like to try
and social scientists. These are things that
social science paper that analyses the same
and test new recipes. I find it relaxing to
several of the engineers and social scien
issues but offers a different perspective or
come home from work and cook – it’s phys
tists in my departments are interested in
way of understanding what is going on. It
ical, repetitive and requires some preci
and already working on, and my position
can be challenging for the students but, ac
sion. Cooking is like doing a complete ex
as a ‘bridge’ is a visible demonstration of
tually, the reviews of the courses are usually
periment within less than an hour and the
this commitment.
very good, and the students welcome hav
results are usually satisfying! To be serious
ing the time and space to think about their
though: I don’t imagine going back to work
LT: Thinking about the meaning and
science in a different way.
in a wet lab. But in my research I do get to
sense of science is time consuming. PhDs or
go and spend time visiting and hanging in
postdocs, however, rarely have any spare
LT: What issues do you study right now?
other labs, which is fun. It’s really the best
time beyond lab work. Which strategies do
Frow: One of the research questions
of both worlds, getting to keep a foot in both
you think are the most promising to encourright now that I’m actively exploring is how
natural and social sciences.
age lab scientists to think outside of their box?
knowledge from engineering and knowl
Interview: Karin Hollricher
LT_515_60_61.indd 61
03/09/2015 14:44
page 62
Lab Times
Job Appointments
5-2015
Postdoctoral or PhD position in Intestinal Lipidomics
The Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG)
and the Center for Regenerative Therapies Dresden (CRTD) invite applications for a position as
Postdoctoral fellow or PhD student in Intestinal Lipidomics
INTERNATIONAL PhD
PROGRAM
Applications are invited for internally
funded PhD student fellowships at the
FMI in Basel, Switzerland. Our research
focuses on epigenetics, mechanisms
of cancer and neurobiology. We employ
state-of-the-art technologies to explore
basic molecular mechanisms of cells
and organisms in health and disease.
Application information:
www.fmi.ch/phd
> Epigenetics
> Mechanisms of Cancer
> Neurobiology
Affiliated with the University of Basel
IN BASEL, SWITZERLAND
Application deadline:
2SZIQFIV , 2015
The project is funded by the European Research Council (ERC Starting
Grant) and aims at the characterization of lipids and lipid antigens involved
in the crosstalk between metabolism, immunity, and cancer in the intestine.
We are looking for candidates interested in applying lipidomics approaches
to the study of lipids in the context of intestinal inflammation and cancer.
The proposed study is a joint project between the groups of Dr. Andrej
Shevchenko at the Max Planck Institute of Molecular Cell Biology and Genetics (www.mpi-cbg.de/research/research-groups/andrej-shevchenko) and
Dr. Sebastian Zeissig at the Center for Regenerative Therapies Dresden
(www.crtdresden.de/research/crtd-core-groups/zeissig). The position offers
an excellent opportunity to join a group of enthusiastic researchers in a
cross-disciplinary environment. Moreover, the CRTD (www.crt-dresden.de)
and the MPI-CBG (www.mpi-cbg.de) provide outstanding facilities for the
proposed studies including a state-of-the art lipidomics facility.
We seek candidates with expertise in analytical chemistry of lipids and, in
case of postdocs, expertise in lipidomics. Funding is available for 3 years.
Salary is according to E13 (100% for postdocs, 65% for PhD students).
Please send your application by September 30th 2015 by e-mail as a single
PDF to: [email protected] and [email protected].
www.fmi.ch
Affiliated with the Novartis Institutes for BioMedical Research
References
1. Olszak et al., Nature. 2014 May 22;509(7501):497-502.
2. An et al., Cell. 2014 Jan 16;156(1-2): 123-33.
3. Papan et al., Anal Chem. 2014 Mar 4;86(5):2703-10.
4. Zeissig et al., Nat. Med. 2012. Jul;18(7):1060-8.
5. Sampaio et al., Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1903-7.
6. Shevchenko et al., Nat Rev Mol Cell Biol. 2010 Aug; 11(8):593-8.
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LT_515_62_66.indd 62
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Conferences
5-2015
page 63
Lab Times
Calendar
2015
21/9-22/9 Strasbourg (FR)
Mitochondria at the Crossroad
– Symposium 2015 of the
MitoCross LabEx Consortium,
Info: http://mitocross.unistra.fr/
symposium-2015
21/9-24/9 Oxford (UK)
12th Conference of the European
Society for Reproductive
Immunology, Info:
http://esri.org.hu/2015-meeting
21/9-25/9 Funchal, Madeira (PT)
17th Congress of European Mycologists, Info: www.mundiconvenius.
pt/eventos/2015/xviicem2015
21/9-25/9 Warsaw (PL)
44th European Muscle Conference: Muscle Research in Health &
Disease, Info: www.emc2015.org.pl
22/9-24/9 Basel (CH)
MipTec 2015: European Conference and Exhibition for Drug
Discovery, Info: www.miptec.com
22/9-24/9 Grenoble (FR)
2nd Symposium Signaling
Through Chromatin, Info: http://
epigenetics.fr/symposium2015
23/9-25/9 Basel (CH)
5th Basel Postdoctoral Network
Retreat, Info: https://postdoc
retreat.biozentrum.unibas.ch
23/9-25/9 Tuebingen (DE)
Novel Concepts in Innate
Immunity, Info: www.innateimmunity-conference.de
23/9-26/9 Dresden (DE)
12th Dresden Symposium on
Autoantibodies: From Autoantibody Research to Standardized
Diagnostic Assays in the
Management of Human Diseases,
Info: www.gfid-ev.de/dsa.htm
23/9-26/9 Šibenik (HR)
Central European Symposium on
Antimicrobials and Antimicrobial
Resistance (CESAR2015), Info:
http://hmd-cms.hr/cesar2015
LT_515_62_66.indd 63
24/9-25/9 Hannover (DE)
3rd International Symposium on
Peripheral Nerve Regeneration,
Info: www.ispnr.eu
24/9-28/9 Ajaccio (FR)
EMBO Conference on Nuclear
Receptors: From Molecules to
Humans, Info: http://events.
embo.org/15-nuclear-receptors
26/9-29/9 Stresa (IT)
Meeting of the International Society for Autonomic Neuroscience
– Bringing the Latest in Autonomic
Neuroscience From Around the
World, Info: www.isan2015.org
27/9-2/10 Elche (ES)
12th International Meeting on
Cholinesterases and 6th International Conference on Paraoxonases, Info: www.12thChE.org
27/9-2/10 Mandelieu-l.-Nap. (FR)
EMBO Conference: The Multidisciplinary Era of Endocytic Mechanics and Functions, Info: http://
events.embo.org/15-endocytic
28/9-30/9 Cambridge (UK)
Abcam Conference on Cancer
and Metabolism Conference
2015, Info: www.abcam.com/
events/cancer-and-metabolismconference-2015
28/9-30/9 Greifswald (DE)
International Symposium on
Sulfation Pathways (SUPA 2015),
Info: www.supa2015.org
28/9-30/9 Heidelberg (DE)
DKFZ-ZMBH Alliance Forum: Tumor
Microenvironment, Metabolism
and Metastasis, Info: www.vwfb.de
28/9-1/10 Berlin (DE)
10th International Conference
on Behaviour, Physiology and
Genetics of Wildlife,
Info: www.izw-berlin.de/234.html
29/9-30/9 Essen (DE)
Supramolecular Chemistry on
Proteins – 1st International CRC
1093 Symposium,
Info: www.uni-due.de/crc1093
29/9-2/10 Goettingen (DE)
6th European Conference
on Prokaryotic and Fungal
Genomics, Info:
www.prokagenomics.org
29/9-2/10 Paris (FR)
EMBO Conference: Genetic Control of Development and Evolution,
Info: www.gene-control-2015.org
29/9-3/10 Porto (PT)
11th International Meeting on
Yeast Apoptosis (IMYA 2015),
Info: www.imya11.com
30/9-1/10 Basel (CH)
14th Annual Biotech in Europe
Forum for Global Partnering und
Investment, Info:
www.sachsforum.com/basel14
30/9-2/10 Copenhagen (DK)
International Conference on One
Health Antimicrobial Resistance
(ICOHAR), Info: http://icohar.org
30/9-3/10 Marbella (ES)
TOLL Conference 2015: Targeting
Innate Immunity, Info: www.
toll2015.org
1/10-3/10 Berlin (DE)
Dual Role of Arthropods in Human
and Animal Health, Info: www.leo
poldina.org/de/veranstaltungen/
veranstaltung/event/2311
1/10-4/10 Estoril (PT)
17th Annual John Goldman Conference on Chronic Myeloid Leukemia: Biology and Therapy, Info:
www.esh.org/conference/17thannual-john-goldman-conference
4/10-9/10 Pultusk (PL)
ESF/EMBO Symposium on
Interaction Between the Immune
System and Nanomaterials:
Safety and Medical Exploitation,
Info: http://nanomaterials.esf.org
5/10-6/10 London (UK)
Cells: From Robert Hooke to Cell
Therapy – a 350 Year Journey,
Info: https://royalsociety.org/
events/2015/10/cells-fromrobert-hooke-to-cell-therapy
5/10-7/10 Berlin (DE)
2nd Next Generation Sequencing
& Bioinformatics Conference,
Info: www.gtcbio.com/conferences
5/10-8/10 Berlin (DE)
Biomarker Summit Europe 2015:
9th Biomarkers in Drug Discovery
& Development & 4th Biomarkers
in Diagnostics, Info:
www.gtcbio.com/conferences
5/10-9/10 Cape Sounio (GR)
EMBO Conference: The DNA
Damage Response in Cell
Physiology and Disease, Info:
http://events.embo.org/15-ddr
Biotechnica 2015:
Biotechnology, Life Sciences and
Lab Technology – Trade Fair,
Info: www.biotechnica.de/home
Labvolution – World of Lab
Technology – Trade Fair,
Info: www.labvolution.de
EMBO-EMBL Symposium: Seeing
is Believing – Imaging the
Processes of Life,
Info: www.embo.org/events
Advances in Lab Automation and
Robotics Conference, Info: https://
selectbiosciences.com/ALR2015
6.10.-8.10.2015, Hannover, Germany
Europe’s No.1
Event for
Biotechnology,
Life Sciences and
Lab Technology
World of Lab
Technology for
the chemical and
pharmaceutical
industries, environmental technology
and the food industry
Two trade fairs.
One exhibition ground.
One admission ticket.
More Information:
www.biotechnica.de
www.labvolution.de
04.09.15 15:12
page 64
Lab Times
Lab Times
Founded 2006. Issue 5, 2015
Lab Times is published bimonthly
ISSN: 1864-2381
Publisher:
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Conferences
5-2015
Genome Engineering Conference,
Info: https://selectbiosciences.
com/GE2015
7/10-9/10 Berlin (DE)
11th VAAM Symposium on Molecular Biology of Fungi, Info: www.
vaam.de/index.php/termine.html
7/10-9/10 Budapest (HU)
Integration of Pharmacogenomics
in Clinical Decision Support –
3rd Conference of the European
Society of Pharmacogenomics
and Personalised Therapy (ESPT),
Info: www.esptcongress.eu
13/10-16/10 Freiburg (DE)
Symposium on Methodological
Challenges in Biomedical
Research, Info: http://portal.unifreiburg.de/imbi/symposium2015
Wellcome Trust Conference on
Infectious Disease Genomics,
Info: https://registration.
hinxton.wellcome.ac.uk/
display_info.asp?id=501
14-16/10 Noordwijk aan Zee (NL)
9th European Meeting on Molecular Diagnostics (EMMD 2015),
Info: www.molecularmeeting.com
7/10-11/10 Isle sur Sorgue (FR)
EMBO Conference on Nuclear
Structure and Dynamics, Info:
http://events.embo.org/15-nucleus
15/10-18/10 Antalya (TR)
2nd International Congress on
Stem Cell and Cellular Therapies,
Info: www.stemcell2015.org
8/10-10/10 Stuttgart (DE)
Bone-Tec 2015 – International
Bone-Tissue-Engineering
Congress, Info: www.bone-tec.com
15/10-18/10 Antalya (TR)
Endobridge 2015: Bridging
the World of Endocrinology,
Info: http://endobridge.org/2015
Cover Photo:
RazoomGames@iStock,
Editing: Kai Herfort
8/10-10/10 Vienna (AT)
International Symposium on
Flaviviruses: Structure and
Immunity, Info: www.virologie.
meduniwien.ac.at/flavi-symp
17-22/10 S. Feliu de Guixols (ES)
EMBO Conference: Exploring the
Genomic Complexity and Diversity
of Eukaryotes, Info: http://events.
embo.org/15-eukaryotes
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8-11/10 Mont-Saint-Odile (FR)
Hormones, Metabolism and
Cancer – 40th Symposium on
Hormones & Cell Regulation, Info:
http://hormones-cell-regulation.eu
EMBO-EMBL Symposium:
The Non-Coding Genome, Info:
www.embo-embl-symposia.org/
symposia/2015/EES15-08
11/10-14/10 Bamberg (DE)
Annual Meeting of the International Cytokine & Interferon Society,
Info: www.cytokines2015.com
19/10-20/10 London (UK)
Chimeric Antigen Receptor
Therapy in Haematology and
Oncology: Current Successes
and Challenges, Info:
www.biochemistry.org/Events
Reporters:
Latika Bhonsle, Steven Buckingham,
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LT_515_62_66.indd 64
Abcam Conference on Epigenetics,
Obesity and Metabolism,
Info: www.abcam.com/EOM2015
EMBO-EMBL Symposium: New
Approaches and Concepts
in Microbiology, Info: www.
embo-embl-symposia.org/
11/10-16/10 Hagoshrim (IL)
Tetrapyrrole Photoreceptors of
Photosynthetic Organisms,
Info: www.fems-microbiology.org
19/10-21/10 Basel (CH)
Annual Biocontrol Industry
Meeting (ABIM 2015),
Info: www.abim.ch
20/10-21/10 London (UK)
Microfluidics Congress, 2nd
Synthetic Biology Congress and
3rd qPCR & Digital PCR Congress,
Info: www.globalengage.co.uk/
microfluidics.html
Missing an event? Let us know:
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BioData World Congress 2015 –
Harnessing the Power of Big Data
in Biomedical Research, Info: www.
healthnetworkcommunications.
com/conference/biodata
21/10-23/10 Leipzig (DE)
World Conference on
Regenerative Medicine,
Info: www.wcrm-leipzig.com
21/10-23/10 Paris (FR)
3rd World Congress on Targeting
Microbiota, Info:
http://microbiota-site.com
17th EMBL PhD Symposium: Just
by Chance? – Randomness and
Variability Shaping Biology, Info:
http://phdsymposium.embl.org
22/10-25/10 Berlin (DE)
3rd International Congress
on Controversies in Stem Cell
Transplantation and Cellular
Therapies, Info: www.comtecmed.
com/costem/2015
26/10-28/10 Paris (FR)
Fungal Cell Wall 2015,
Info: www.fcw2015.org
26/10-29/10 Edinburgh (UK)
Organelle Crosstalk in Membrane
Dynamics and Cell Signalling,
Info: www.biochemistry.org/Events
28/10-30/10 Berlin (DE)
6th World Congress on Targeting
Mitochondria, Info:
www.targeting-mitochondria.com
Wellcome Trust Conference on
Functional Genomics and Systems
Biology: From Model Organisms
to Human Health, Info: https://
registration.hinxton.wellcome.
ac.uk/display_info.asp?id=517
28/10-30/10 Perugia (IT)
Microbial Diversity 2015: the
Challenge of Complexity, Info:
www.fems-microbiology.org
EMBL Conference on Cancer
Genomics, Info: www.embl.de/
training/events/2015/CAN15-01
04.09.15 15:12
Conferences
2/11-4/11 Munich (DE)
Bio-Europe 2015 – Partnering
Conference Serving the Global
Biotechnology Industry, Info:
www.ebdgroup.com/bioeurope
2/11-4/11 Weimar (DE)
19th Joint Meeting „Signal
Transduction – Receptors,
Mediators and Genes“, Info:
www.sigtrans.de/meeting.html
3/11-5/11 London (UK)
Antibiotic Resistance and
Antibiotic Alternatives: Looking
Towards the Future, Info: www.
regonline.co.uk/Antibio2015
3/11-5/11 Milan (IT)
Abcam Conference on PI3Klike Protein Kinases, Info:
www.abcam.com/Milan2015
4/11-5/11 Birmingham (UK)
Lab Innovations 2015,
Info: www.easyfairs.com/
index.php?id=65877
4/11-5/11 London (UK)
10th Conference on Meningitis
and Septicaemia in Children and
Adults, Info: www.meningitis.org/
conference2015
4/11-6/11 Tutzing (DE)
ATMP 2015 – Issues and
Challenges from Bench to
Bedside: Production, Analytics &
Regulatory Aspects of Cell-based
Therapies, Info: http://events.
dechema.de/ATMP2015.html
Emerging Biotechnologies: Hype,
Hope & Hard Reality – EMBO/
EMBL Science & Society Conference, Info: http://events.embo.
org/science-society-conference
6/11-8/11 Cluj-Napoca (RO)
International Conference on Molecular Biology: Current Aspects
and Prospects, Info: http://
icmb.conference.ubbcluj.ro/en
8/11-11/11 Berlin (DE)
Basic Epigenetic Mechanisms
in Cancer – Conference of the
European Association for Cancer
Research (EACR), Info:
http://eacr.org/basicepigenetics
LT_515_62_66.indd 65
9/11-10/11 London (UK)
Industrial Applications of Metal–
Microbe Interactions – Focused
Meeting of the Society for
General Microbiology (SGM),
Info: www.sgm.ac.uk/conferences
Clinical Practice and Targeted Therapies
in Personalized Medicine
5th Munich Biomarker Conference
December 1st – 2 nd, 2015
9/11-10/11 London (UK)
Cell & Gene Therapy Congress
2015 & 4th Annual Cell Culture
& Bioprocessing Congress & 2nd
Annual Stem Cell Congress, Info:
www.celltherapy-congress.com
RAMADA Hotel & Conference Center München Messe
9/11-11/11 Basel (CH)
11th Annual European Antibody
Congress – Discover, Develop,
Get to Market, Info: www.
terrapinn.com/conference/
european-antibody-congress
Keynote Speakers:
Yves Champey | ITEEC, Genopole,
Paris | France
Thomas Deisboeck | ThinkMotu LLC.,
Boston | USA
Michael Hallek | University Hospital,
Cologne | Germany
Lorenz M. Mayr | AstraZeneca,
Cambridge | UK
Kári Stefánsson | deCODE genetics,
Reykjavík | Iceland
9/11-11/11 Dresden (DE)
International Conference on Crossing Biological Barriers – Advances
in Nanocarrier Design for Targeted
Drug Delivery, Info: http://events.
dechema.de/CBB2015.html
Interdisciplinary conference program
12/11-13/11 London (UK)
3rd Annual Single Cell Analysis
Congress, Info:
www.singlecell-congress.com
EMBO-EMBL Symposium:
Biological Oscillators – Design,
Mechanism, Function, Info:
www.embo-embl-symposia.org/
One-to-one partnering
Sponsoring options and exhibition
Panel discussions and poster session
Register now - Early bird until October 9th, 2015
11/11-12/11 Berlin (DE)
3rd International mRNA Health
Conference, Info:
www.mrna-conference.com
11/11-12/11 Trondheim (NO)
1st National Symposium on
Biodiversity and DNA Barcoding,
Info: http://norbol.org/
symposium2015
page 65
Lab Times
5-2015
Goldsponsor
www.bio-m.org/mbc
15/11-17/11 Borstel (DE)
Lipidomics Forum 2015, Info: http:
//lipidomics-forum.fz-borstel.de
16/11-18/11 Montreux (CH)
NanoBioTech-Montreux
Conference, Info:
www.nanotech-montreux.com
EMBL/Stanford Conference on
Personalised Health, Info: www.
embl.de/training/events/2015
17/11-19/11 London (UK)
The 2015 Innate Immunity
Summit, Info: www.regonline.
co.uk/Innate2015
26/11-27/11 Durham (UK)
Metal-Related Antimicrobials
Event, Info: http://
prospect.rsc.org/MiB_NIBB/
metal-related-antimicrobials
29/11-1/12 Munich (DE)
36th New Phytologist Symposium
– Cell Biology of Plant–Microbe
Interactions, Info: www.
newphytologist.org/symposiums
1/12-2/12 Munich (DE)
5th Munich Biomarker
Conference,
Info: www.m4.de/mbc
12/11-15/11 Sitges (ES)
EFB Conference on Microbial
Stress: From Molecules to
Systems, Info: www.efb-central.
org/index.php/microbial_stress
21/11-23/11 Glasgow (UK)
Action on Infection – Federation of
Infection (FIS) Societies Meeting,
Info: www.actiononinfection.com
1/12-3/12 London (UK)
Pathology 2015: Molecular and
Cellular Pathology / Diagnostic
and Disease Pathology / Cancer
Pathology, Info:
www.regonline.co.uk/Path2015
13/11 London (UK)
Modelling Approaches in
Molecular Signalling,
Info: http://yls2015.org.uk
23/11-25/11 Vienna (AT)
Microbe-Assisted Crop Production
– Opportunities, Challenges and
Needs, Info: www.micrope.org
2/12 London (UK)
Abcam Meeting on Epigenomics:
New Marks, New Horizons,
Info: www.abcam.com/events
04.09.15 15:12
page 66
Lab Times
2/12-3/12 Brussels (BE)
Cell Therapy Manufacturing
and Gene Therapy Congress,
Info: www.informa-ls.com/event/
celltherapy15
2/12-4/12 Berlin (DE)
Revealing Prometheus‘ Secrets:
Current Technologies for Tissue &
Organ Regeneration – 6th PhD
Symposium of the Berlin-Brandenburg School for Regenerative
Therapies (BSRT), Info:
www.bsrt-phdsymposium.de
MetaboMeeting 2015 –
Partnering with the Metabolic
Profiling Forum (MPF), Info:
https://selectbiosciences.com/
Metabo2015
8/12 London (UK)
New Developments in Protein
Structure Modelling for
Biological and Clinical Research,
Conference on Target Validation
Using Genomics and Informatics,
Info: https://registration.hinxton.
wellcome.ac.uk/Conferences.wt
8/12-10/12 London (UK)
The Science of Pain and its
Management, Info:
www.regonline.co.uk/pain2015
14/12-16/12 Berlin (DE)
IUBS 2015 – Frontiers in Unified
Biology: 32nd IUBS International
Union of Biological Sciences –
General Assembly and Conference, Info: www.iubs2015.org
15/12-17/12 London (UK)
Pharmacology 2015, Info:
www.bps.ac.uk/meetings/
Pharmacology2015
2016
5/1-7/1 London (UK)
Biobanking 2016, Info: www.
regonline.co.uk/banking2015
19/1-21/1 London (UK)
Bacteriophage 2016, Info:
www.regonline.co.uk/Phage2016
LT_515_62_66.indd 66
Conferences
5-2015
Epigenetics in Drug Discovery,
Info: http://selectbiosciences.
com/EGDD2016
EMBO-EMBL Symposium: A New
Age of Discovery for Aquatic
Microeukaryotes, Info: www.
embo-embl-symposia.org/
28/1-29/1 London (UK)
The New Bacteriology – A Royal
Society Meeting, Info: https://
royalsociety.org/events/2016/1/
new-bacteriology
30/1-5/2 Lucca/Barga (IT)
Gordon Research Seminar and
Conference: Ligand Recognition
& Molecular Gating – Molecular
Basis of Ligand Recognition
and Gating in Transmembrane
Signaling and Transport,
Info: www.grc.org/programs.
aspx?id=12689
2/2-4/2 London (UK)
Cell Culture 2016, Info:
www.regonline.co.uk/Cell2016
Selectbio Conference on
Antibodies in Drug Discovery,
com/ABDD2016
Wellcome Trust Conference
on Mouse Models of Disease:
Improving Reproducibility of
Pathology Endpoints in Challenge
Models, Info: https://registration.
hinxton.wellcome.ac.uk/
display_info.asp?id=488
14/2-16/2 Rehovot (IL)
EMBO Conference: From Host
Genomes to Microbiome –
Immunity in the Genomic Era,
Info: www.weizmann.ac.il/
conferences/NGI2016
15/2-16/2 Lausanne (CH)
Life Sciences Switzerland
Meeting 2016: Interdisciplinary
Sciences, Info:
www.ls2-annual-meeting.ch
Flow Chemistry Europe 2016:
6th International Conference of
the Flow Chemistry Society, Info:
https://selectbiosciences.com/
FCE2016
Gordon Research Seminar
and Conference: Angiotensin,
Info: www.grc.org/programs.
aspx?id=15143
23/2-24/2 Munich (DE)
Cell Culture World 2016 –
Enhancing and Innovating
Your Cell Culture Process, Info:
www.terrapinn.com/conference/
cell-culture
Gordon Research Conference:
Glycolipid & Sphingolipid Biology
– Glycolipid and Sphingolipid
Homeostasis and Function in
Health and Disease, Info: www.
grc.org/programs.aspx?id=12366
EMBO Conference on Visualizing
Biological Data (VIZBI 2016),
Info: www.embo.org/events/
conferences
11/3-13/3 Athens (GR)
International Conference on
Aging and Hematological
Malignancies: Biology and
Therapy, Info: www.esh.org/
conference/internationalconference-on-aging
Gordon Research Seminar and
Conference: New Antibacterial
Discovery & Development –
Enabling the Next Generation of
Antibacterial Drugs, Info: www.
grc.org/programs.aspx?id=14326
14/3-15/3 London (UK)
Genetics in Forensics Congress,
Info: www.forensicgeneticscongress.com
15/3-16/3 Madrid (ES)
Lab-on-a-Chip Europe,
com/LOACE2016
More events at www.labtimes.org/labtimes/calendar
15/3-16/3 Madrid (ES)
Single Molecule & Single Cell Analysis, Info: http://selectbiosciences.
com/SMSCA2016
BMP Signalling in Cancer, Info:
15/3-17/3 London (UK)
Immunosuppression
Summit 2016: Problems of
Immunosuppression and
Overcoming Them, Info: www.
regonline.co.uk/Immuno2016
29/3-30/3 Valencia (ES)
6th International Conference
on Bioinformatics,
Info: http://bioinformatics.
conferenceseries.com
31/3-2/4 Mosbach (DE)
67th Mosbach Kolloquium:
Protein Design: From First
Principles to Biomedical
Applications, Info: www.gbmonline.de/detail/events/id-67mosbacher-kolloquium.html
2/4-6/4 Soelden (AT)
18th International Neuroscience
Winter Conference, Info: www.
winterneuroscience.org/2016
EMBO-EMBL Symposium: Tumour
Microenvironment and Signalling,
Info: www.embl.de/training/
events/2016/ETC16-01
4/4-5/4 Chester (UK)
The Grey Area: Ageing in Extracellular Biology and Pathology,
4/4-5/4 Chester (UK)
Quantitative Proteomics and
Data Analysis, Info:
Selectbio Conference:
Organ-on-a-Chip Europe,
com/OOACE2016
6/4-10/4 Leipzig (DE)
10th International Congress
on Autoimmunity, Info: http://
autoimmunity.kenes.com
04.09.15 15:12
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5/2015
CELL SIGNALING TECHNOLOGY
EPIGENETICS:
DISCOVERY THROUGH VALIDATION
69
CST antibodies for epigenetic-related targets,
including histone modifications, epigenetic
regulators, and general transcription factors.
22
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to ENCODE* Consortium guidelines.
Validated Tools for Discovery:
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additional applications like IHC, Flow, IF and WB.
Learn more at: www.cellsignal.com/epigeneticdiscovery
*Landt S.G. et al. (2012) Genome Res. 22, 1813–1831.
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EMBO goes East

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