We have entered an age of
austerity that, given the fecklessness of the political classes, won't end any
time soon. Against that backdrop, the global science community must decide how
to succeed with less money.
Major changes in the way
science is funded and conducted are needed to ensure the most pressing
scientific problems are addressed by the best scientists. The patients who rely
on the biomedical innovation ecosystem deserve nothing less, and the taxpayers
who foot the bill should be demanding it.
Basic science is a classic
example of a public good that should be funded by government. Indeed, it doesn't
take much scratching to find publicly funded research underlying virtually
every biomedical innovation of the modern era.
Yet publicly funded research is
but a part of a complex innovation ecosystem. It produces maximum value to
society only when it dovetails with private sector institutions capable of
exploiting the scientific opportunities it creates.
With very few exceptions,
medical breakthroughs that began with publicly funded discoveries would not and
could not have occurred without the private sector making enormous investments,
taking financial risks and applying its own scientific inventiveness as well as
An example of this link is HCV. In 1997, researchers funded by
NIH published in Science that they had figured out how to clone
the virus. That in turn allowed research teams from multiple institutes,
including NIH's National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), to
figure out how to culture HCV in 2005. This basic science then made it possible
for drug companies to pour billions of dollars into developing targeted
treatments that actually cure some patients.
In this manner publicly funded
basic research has played a huge role in creating the biotechnology industry.
Seeking to catch up, China,
Korea, India and other countries aiming to participate in the 21st century
economy have been investing more in basic science research and science training
with the aim of building biopharma industries of their own.
But now, a number of countries
are in austerity mode, and science budgets are increasing moderately, if at all
(see "R&D Trajectories," A3).
In the U.S., budget
sequestration could lead NIH - by far the world's biggest source of public
research money - to fund 2,300 fewer new grants in FY13, slashing a quarter of
last year's total. The burden would fall most heavily on first-time grant
applicants, NIH Director Francis Collins told a Senate committee in March.
Even if Congress spares NIH
from cuts, there is no chance the next budget will increase enough to reverse
the erosion in science purchasing power experienced over the last four years.
No other country funds
bioscience for as long or as generously as the U.S., and no other country has
as much flexibility in terms of career options for scientists. But NIH's
approach to training and research funding has become sclerotic and hasn't kept
up with changes in the real world.
Markers of sclerosis, not just
at NIH but also within academia, include the fact that a smaller and smaller
proportion of young researchers get funding to do independent work, and the fact
that a separate pool of money had to be set aside to fund potentially
Neither has academia kept up
with the changing world. Indeed, the university research model is a house of
cards based on the idea that public funds will increase into infinity.
China, Korea, India, Brazil and
other countries investing to develop basic biomedical science engines have
their own problems, including in some cases lack of a research tradition and
lack of a developed industry that can translate and develop novel discoveries.
But these countries have an
opportunity to do it differently, learning from what does and does not work at
As other countries improve
their scientific base, resetting the system in the U.S. will be crucial if
biomedical research and a thriving biopharmaceutical industry are to be drivers
of national competitiveness.
But more money will not be the
answer in the age of austerity.
Put simply, the $30 billion American taxpayers give NIH
annually, the more than $10 billion EU citizens invest in health-related
R&D, and the billions donated by philanthropies, $2 billion from the Wellcome
Trust and Howard
Hughes Medical Institute alone, must be enough.
It is imperative that the
global research enterprise find ways to create lasting value for society with
the resources available. This 20th Back to School Commentary argues there is no
reason it can't. While the will of entrenched interests may be lacking, it is
not hard to identify fat in the system. Moreover, the numbers show excessive
money is being spent on science that will not yield transformational value,
while drip feeding innovation the public good requires.
As has been the case in
industry since the meltdown began, righting the ship may mean the absolute size
of the life sciences establishment has to shrink.
But just as Back to School
previously has argued that rebasing is good for industry, it also will be
healthy for the scientific endeavor. If and when the biomedical research
enterprise restructures so that it can live - and thrive - with current funding
levels, it will be in a much better position to justify future funding
Any discussion of saving
publicly funded basic research must start by acknowledging the system does
consistently produce important discoveries that lead to broad improvements in
overall health and quality of life.
It is nonetheless clear there
is fat in the system that diverts resources from the conduct of research; that
not enough transformational ideas get funded; that not enough young researchers
are permitted to do their own work; and that there is too little collaboration
between countries, institutions and individuals.
While no one who understands
and values the scientific enterprise would sensibly argue in favor of a
top-down system that prescribes what work scientists should do, it is still
true that the current approach is not strategic enough. And even with the
recent explosion of precompetitive consortia and corporate-academic
collaborations, there is still too little interaction between those who perform
basic research and those who translate basic discoveries into new treatments.
Though not all of these
problems are exclusive to NIH, many are most easily illustrated by looking at
NIH because of its size and the amount of information it discloses publicly.
Ironically, some of these
problems were caused by a doubling of the NIH budget from 1998 to 2003.
The doubling was Miracle Grow
for university biomedical research programs, which responded with an explosion
of infrastructure and activity as if the gusher of money would continue
According to a paper published by researchers from the Association
of American Medical Colleges in the New England Journal of Medicine
in September 2007, in the eight years prior to the doubling (1990-97), medical
colleges spent an aggregate annual average of $400 million on construction and
renovation of biomedical facilities.
In a 2002 survey, AAMC schools
said they expected to spend an annual average of $1.9 billion on construction
and renovation over 2003-07. While an estimate, those amounts were mostly
already committed in multi-year construction contracts.
Universities and institutes
also increased the number of faculty and trainees in response to the doubling
of NIH's budget.
The predictable result of the
increase in academic research capacity was a surge in grant applications to NIH
that began near the end of the doubling period and has continued to the
present. NIH reviewed 18,807 new grants in FY98. By FY03 that figure was
28,355, and last year it was 43,639 (see "Fear of Failure").
However, NIH funding increased
by 2% annually between FY03 and FY11, while the cost of doing research as
measured by the Biomedical Research and Development Price Index (BRDPI)
increased 4% a year.
The BRDPI is calculated each
year by the Bureau of Economic Analysis in the U.S. Department of Commerce;
however, it is autocorrelated with research institutions driving up payroll and
overhead in anticipation of future hikes in the NIH budget.
But the NIH budget also has
lagged the Consumer Price Index, which has increased 3% annually from 2003-11.
By this benchmark, NIH's budget has actually decreased 1% annually in real
terms, from $24.1 billion in FY03 to $22.4 billion in FY11 using 1998 dollars (see
"Facing Reality," A5).
Meanwhile, universities and
institutes have been relying heavily on NIH to support their bloated
Data from the University of
California office of the president show that over two decades, the number
of senior administrators in the UC system has grown four times faster than the
number of teachers. In 1993, there were 2.5 faculty members to one senior
manager. The ratio is now 1:1.
In FY10, on average only 73% of
NIH research grants went to project-related costs, while 27% went to overhead,
including facilities and administration, at the institution where the research
But averages never tell the
whole story. Academics whose institutions receive NIH grants and drug
developers who have contracted with academics for research told BioCentury
that, at some of the larger universities, the overhead charges can routinely be
50% to more than 100% of the project-related costs. A $250,000 research project
could come with more than $250,000 in overhead charges.
In many cases, NIH grant monies
are used to pay for 100% of faculty salaries. And multiple grants that are
awarded to a single PI would each have overhead built in, presumably covering
the same laboratory facilities, even if salary is pro-rated for each project.
The increasing numbers of
applications, coupled with NIH's reduced purchasing power, have had disturbing
effects on academic researchers.
In FY02, NIH reviewed 24,403
new research project grant applications and approved 6,505 of them, for a 26.7%
success rate. The average annual funding per grant was $304,951.
By FY11, the number of new
applications had increased to about 43,639 and there were 6,629 awards,
producing a 15.2% success rate. The average annual funding per grant was
$406,980, or $325,491 in 2002 dollars.
The falling success rates
amplified a worsening trend toward limiting access to NIH money. The average
age at which a scientist receives his or her first independent grant had
already begun to climb before the doubling. In 1970, the average age for a
first R01 grant was 35. By 1980 it had crept up to 37. It rose to 39 in 1990,
hit 42 in 2000 and has been steady for the last dozen years.
This would be an indicator that
something was wrong even without the imperatives of austerity.
The age distribution of
NIH-supported PIs tells the same bleak story.
"In 1980, less than 1% of
PIs were over age 65, and now PIs over age 65 constitute nearly 7% of the
total," noted Sally Rockey, NIH's deputy director for extramural research,
in a recent blog posting. "In parallel, in 1980, close to 18% of all PIs
were age 36 and under. That number has fallen to about 3% in recent years."
The protracted adolescence of
biomedical scientists is imposing enormous unseen opportunity costs. Younger
scientists are much more likely than their mentors to be familiar with a wide
range of technologies and ideas outside their area of specialization. A system
that keeps scientists occupied on someone else's research until after their
42nd birthday creates evolutionary pressure for docility and against
It also keeps a high proportion
of the workforce in a kind of postadolescent holding pond, rather than sending
them into the world during the very stage of their careers when they should be
moving up the ladder.
The numbers of people getting
Ph.D.s in biomedical science in the U.S. has more than doubled in the last 20
years. There are more young women and men doing science than ever, they just
aren't doing their own science.
State University economist Paula Stephan noted in How Economics
Shapes Science, U.S. science operates on a pyramid scheme. The best way for
PIs to ensure future success and the production of research that will enhance
their reputations is to recruit as many talented postdocs and graduate students
as possible to work in their labs.
Stephan is no mere pundit, having served on boards for NIH,
Research Council and the National
Science Foundation (NSF).
In exchange for this
dedication, postdocs supposedly are receiving valuable training that will lead
them to tenure-track academic positions and one day to become PIs themselves.
But their mentors have no incentive to inform postdocs there cannot possibly be
enough tenure-track positions to absorb them.
The result is that after
dedicating many years to graduate school and postdoc training, many people who
earn Ph.D.s in biomedical science never work in the profession.
This represents an immense
waste of talent and resources - and money.
The knock-on effects don't stop
Middle-aged scientists who have
spent their entire careers working for other scientists are desperate to get
their first grant, so the incentive is to play it safe by submitting an
application that is interesting enough to appeal to the majority of the
reviewers, but not so cutting-edge they decide it is unlikely to succeed.
It is an open secret that the
most effective way to improve one's chances of receiving a grant is to have
already performed all or most of the work described in the application. This
kind of gamesmanship was routine in the Soviet Union, where there were strong
incentives to hit five-year plan targets and few rewards for unexpected
accomplishments. The USSR wasn't a font of innovation.
We know from the biotech
industry, and from Silicon Valley, that failure is almost a prerequisite for
success. But there is little tolerance for and certainly no reward for failure
in the current NIH grant-making structure. Safe science isn't likely to be
This is not to deny the
incredible biomedical breakthroughs that have come out of the U.S. system.
Rather, it is to say that the kinds of inefficiencies that were tolerable in an
era of plenty now will be dead weight in an era of austerity.
While the NIH peer review
system is often cited as the gold standard by researchers from other countries,
U.S. researchers frequently note it is a conservative old boys' network. Less
frequently, they say the peer-review network has too many third-rate reviewers
who give high scores to mediocre proposals.
Either way, the fact that NIH
has had to create four grant programs to fund so-called "high risk-high
reward" science provides evidence that the peer review system favors safe,
predictable research over innovative, paradigm-testing projects.
NIH admits as much on its own
website: "NIH has traditionally supported research projects, not
individual investigators. However, complementary means might be necessary to
identify scientists with ideas that have the potential for high impact, but
that may be too novel, span too diverse a range of disciplines, or be at a
stage too early to fare well in the traditional peer review process."
The website goes on: "To
address this, the NIH Common Fund created three companion awards, the NIH
Director's Pioneer, New Innovator, and Transformative Research Award, to encourage
creative, outside-the-box thinkers to pursue exciting and innovative ideas
about biomedical research. A fourth award in the High-Risk Research Program,
the NIH Director's Early Independence Award (EIA), was created in fiscal year
2011 to support exceptional early career scientists who possess the intellect,
scientific creativity, drive, and maturity to flourish independently
immediately following their graduate training, eliminating the need for
traditional post-doctoral training."
In FY11, these four programs
awarded 89 new grants totaling an underwhelming $147 million.
competition for research grants creates a second set of anti-innovation
evolutionary pressures. Virtually everywhere, not just at NIH, academic
scientists spend at least as much time applying for funding as doing research.
And there is far too little
collaboration between scientists, institutions and countries on the most
compelling questions that require a diversity of scientific disciplines and
approaches, as well as the economies that are gained from pooled resources and
reduction in duplication of efforts.
The path forward
Fiscal austerity in the U.S.
and Europe is widely viewed within the science establishment as the cause of
the crisis. But it actually should be the impetus for fundamental changes that
will make the global science enterprise stronger and more productive.
Even NIH's Collins has
concluded that just putting in more money isn't the answer. There are those who
disagree with his solution - dedicating a new center to translational research -
but at least he's thinking about how to get a bigger and faster return from the
nation's investment in biomedical research.
In any case, hope is not a
strategy. And muddling through until the economy improves and governments
become more generous is not a viable option.
Some of the urgently needed
changes are obvious, like cutting funding for pseudo-science.
NIH's Center for Complementary
and Alternative Medicine (NCCAM) is an obvious example. It was established
because Sen. Tom Harkin (D-Iowa) and a couple of other members of Congress
firmly believe in the power of bee pollen and cow colostrum.
Over $1.2 billion has been
spent on NCCAM over the last decade, and it is set to receive $120 million next
year. NCCAM has funded a depressing catalog of hypotheses, such as the ideas
that smelling lavender or lemon will promote wound healing and coffee enemas
will cure pancreatic cancer. It also has given financial support and
intellectual stature to training programs for homeopathy.
But while eliminating
pseudo-science would be intellectually satisfying, freeing up $120 million a
year from the NIH budget is little more than looking under the sofa cushions
for loose change.
Key opportunities for emerging
science establishments throughout the world, and challenges for the U.S. and
EU, include making publicly funded science as nimble as the private sector it
feeds into; making more science directly relevant to medical product
developers; and supporting and enabling new generations of scientists.
The overarching objectives for
those who control the public purse should be to prioritize basic over clinical
research; prioritize individual investigators over top-down big science; and
create a bigger marketplace of ideas.
In the U.S., for example, huge
amounts of money could be made available for basic research - and for
translational research - by reducing spending on clinical research. In FY12,
NIH estimates it will spend about $3.1 billion, or 10% of the budget, on
This means there should be
limits on the kinds of clinical research government conducts and funds. These
limits are based on practicality rather than principle: clinical research is
phenomenally expensive and, with a few exceptions, government doesn't do it
Clinical research shouldn't be
contemplated unless there is a clear and compelling need for the results, and a
plan for rapidly translating them into patient benefit.
If and when government funds
clinical research, trials should be done only where industry clearly has no
incentive to do the work, and they should be designed to produce results that
could be transformative.
The flood of activity unleashed
by the Orphan Drug laws throughout the world proves that there is very little
truth in the argument only government will invest in the search for treatments
for rare diseases.
On the other hand, industry is not going to fund clinical
trials comparing the safety and efficacy of medical procedures. And industry is
unlikely to fund the kinds of trials the National
Cancer Institute has run to optimize the sequencing and dosing regimens
of already approved drugs.
Whenever possible, government
funding for clinical research should be contingent on validation by co-investment
by industry and/or patient philanthropies.
Nor should government be in the
business of funding clinical R&D with the goal of getting new drugs
approved - it isn't good at it, and there is little chance that the consensus
processes required by government could be consistently successful.
Importantly, getting government
out of the clinical trial business means industry must accept its obligation to
conduct and/or fund the downstream work that is necessary to translate basic
research discoveries into treatments.
Countries that lack a well
developed biopharmaceutical industry could be an exception. There, it may be
appropriate for governments to fund more translational or clinical work.
Singapore, for example, has
pharmaceutical manufacturing but lacks drug discovery and development, venture
backing and the entrepreneurial spirit that would drive researchers to start
Thus, according to Francis
Yeoh, "the funding mechanism scales have been tipped to incentivize
Yeoh stepped down in July as head of the Singapore
National Research Foundation.
Public science funders also
should prioritize individual investigators or collaborations of investigators
over top-down big science. It doesn't make sense to think of most life sciences
research problems as "moon shots" or Manhattan Projects that can be
solved primarily with large infusions of money, a great deal of organizational
and logistics expertise, and some applied engineering. The human genome project
was a successful exception, but it is not the rule.
At the same time, public
science funders need to find ways to create a bigger marketplace of ideas, by
funding more breakthrough science, funding multidisciplinary research and
funding talented young scientists with good ideas without shackling them to
their mentors indefinitely.
More fundamental discoveries
that will lead to solutions for critical unmet medical needs will come from
small projects, sometimes from previously unknown researchers working in
institutions lacking prestige.
Accomplishing these objectives
will require specific actions, described in more detail in this essay.
Within basic science, there
should be more strategic ways of setting priorities based on societal need. This
should include formal mechanisms for translational scientists and drug
developers to tell basic researchers what specific questions are holding them
back, and there should be funds dedicated to research that will answer those
At the same time, the peer
review system needs to be revamped and to make room for mechanisms that support
bold, innovative ideas.
Meanwhile, a much greater
proportion of public funds should be used for research, not for administrative
overhead and facilities. When tools and facilities are needed, public money
should be spent whenever possible on large-scale resources that many can use.
In terms of human capital,
training has to be revamped to reduce money that now is spent to create a
surfeit of scientists, and to allow the best of them to conduct independent
research earlier in their careers.
Finally, the adaptation to
austerity also should result in more collaboration, not only on the relatively
small scale between and among investigators and institutions, but also on a
much larger scale between governments.
While it is harder to identify
how this will happen, Back to School argues austerity itself will force the
Within basic science, there
should be more strategic ways of setting priorities based on societal need.
This should include formal mechanisms for translational scientists and drug
developers to tell basic researchers what specific questions are holding them
back, and there should be funds dedicated to research that will answer those questions.
It is essential to preserve the
independence of academic investigators, and attempts to centrally impose topics
and questions would be disastrous. At the same time, the justification for
government investment in life sciences research is that it supports medical
However, academic researchers
spend little time, if any, with the scientists who are working to turn their
discoveries into new therapies.
Publicly funded scientists
should spend a lot more time with the people and institutions that translate
their work into products, and to explicitly orient more of their work to
solving puzzles that are preventing the translation of scientific discoveries
This doesn't mean abandoning
basic science for translation. It means that translational work raises basic
science questions that need to be answered.
"Society has to think about how it wants to spend money
efficiently to solve its most significant challenges. Where we are faced with
an aging population in this part of the world, in other parts of the world we're
tasked with addressing significant chronic and infectious diseases. The
question is how do we use the resources we have to solve the world's questions,"
said Paul Stoffels, worldwide chairman of pharmaceuticals at Johnson
faster together and then developing specific products will be good for
industry, because then everyone will be at a higher level together and then
they can compete on how to get products to market," he added.
According to Joshua Boger, former CEO of Vertex
Pharmaceuticals Inc. and chair of the board of fellows at Harvard
Medical School, a challenge for basic research should be to answer the
question: "Who is waiting for the results of my work?"
Science funders and academic
scientists, Boger said, "are not giving a lot of thought to organizing how
we are investing in research. They are not asking if we are orienting basic
research objectives around questions that the folks who are trying to translate
basic research into societal benefit are asking."
The rigor and relevance of
basic biomedical research would be enhanced substantially if the system were
more tuned to reward investigator-initiated research that answered the
question, "who is waiting for the results?"
According to Yeoh, during the
current funding cycle in Singapore, some grants are available only if there is
an industry partner. Also, some large grants ($10 million) are earmarked
specifically for interdisciplinary teams of scientists.
Singapore has also established "national
innovation challenges" where additional research is needed in a particular
area, and the NRF will direct some percentage of funding toward that larger
As a benchmark, in the U.S.,
about 13% of research project grants in 2011 were awarded in response to
requests for applications (RFAs) issued by institutes within NIH for proposals
in targeted areas. These grants accounted for 24% of total research project
The problem is that most
priority setting is carried out by members of the extramural research
community, and doesn't include stakeholders with hands-on knowledge of how to
build the solutions.
Institute of Allergy and Infectious Diseases (NIAID) is part way there:
priorities are set by an 18-member council comprising 12 researchers and six
laypeople representing people living with disease.
While patient involvement is a
good start, the process would be strengthened by incorporating more points of
view, especially those of translational and clinical scientists, and those
working on drug discovery and development in industry.
Among its four strategic objectives, the National
Institute of Mental Health (NIMH) says it aims to "strengthen the
public health impact of NIMH-supported research" - an admirable goal.
However, the description of how
it proposes to do so is bland to the point of being meaningless: "Through
research, evaluation, and collaboration, we will further develop the capacity
of the Institute to help close the gap between the development of new,
research-tested interventions and their widespread use by those most in need."
NIMH does note its success will
depend on collaborating with all stakeholders in the field of mental health. It
lists these stakeholders as payers, service providers, patients, families,
advocacy groups and professional organizations.
Scientists and companies that
actually develop new therapies are not on the list. But those are precisely the
people and organizations who are the first to know if a basic research finding
is panning out in practice, or if it is raising new questions that need to be
answered before there is a path forward.
"In neuroscience, we're
working on how to go to the next stage," said Stoffels. "We should
collaborate more between the entire community from basic science to companies
to identify initial steps - what do you need to know - biomarkers, clinical
Stoffels told BioCentury: "I
went to NIMH, and we had a discussion about how to do this. That was 18 months
ago. A lot of discussions are going on. What we need is for both government and
industry to say this collaboration needs to happen, so that the science would
Jim Greenwood, president and
CEO of BIO, agreed that the missing link between academic scientists,
NIH and industry is a way to communicate questions that arise in applied
research back to scientists working on basic research - especially when studies
fail for unknown reasons.
that allows scientists to independently pursue novel thinking is "a very
important thing for academic researchers to be involved in and for the federal
government to fund - but it is not the only thing necessary to get the job
done," he said.
questions can be developed as a direct result of failures in the clinic and can
be reviewed by NIH, which will know which academic researchers are following
their noses in this area and might be interested in working on them," he
Providing funds for research
aimed at answering those questions is a way to "make sure tax-funded
research has the greatest likelihood of resulting in medical products,"
Although it is focused on a different type of scientific
question, the National
Center for Advancing Translational Sciences (NCATS) could provide a
model for how NIH and industry can work together to identify priorities without
devolving into a top-down, centrally directed approach.
"We are working with NIH
on NCATS and helping define what industry thinks would be most useful,"
For example, in May, NCATS
announced its first initiative would be to partner with pharmas to repurpose
compounds. Greenwood said BIO thinks it would be more useful for NCATS to work
on broad studies that would help modernize clinical trials and clinical
development, rather than conducting studies on a particular molecule.
Reforming peer review
The peer review system needs
to be revamped and to make room for mechanisms that support bold, innovative
Expert review is intended to ensure that the best scientific
proposals from diverse research fields are identified and funded. Large
organizations conduct peer review of project proposals and then fund those with
the highest scores for 3-5 years, after which scientists may apply for a
renewal grant. NIH and the European
Research Council (ERC) predominantly use this model (see "Drawing
the Payline," A8 & "High Risk, High Gain," A9).
But peer review only works with
the participation of engaged high-caliber reviewers, and to be successful the
system must be structured to ensure innovation is properly recognized as a
criterion of excellence.
This is an issue that
researchers in emerging economies are acutely aware of.
"The problem is that if the whole system is producing
science at a particular level, this is the system that will be judging the
proposals. You are in a kind of trap where average people are judging average
projects, and it's difficult to get rid of that [mindset] and drive excellent
projects," said Kleber Franchini, director of the Brazilian
Biosciences National Laboratory.
In Korea, the government is building a new Institute for
Basic Science that plans to have 3,000 researchers and staff based at 50
newly established research centers by 2017. According to Ulf Nehrbass, CEO of Institut
Pasteur Korea, the goal is to recruit "excellent people meant to
have the freedom to explore within the constraints of peer review."
But in countries with a
tradition of excellence in biomedical science, conservatism in peer review can
stifle innovation. Conservatism is especially pernicious when only a small
percentage of top applications are eligible for funding and innovative ideas
can so easily miss the cut.
This is reflected in oft-heard
criticisms of NIH: that peer reviewers demand too much preliminary data, that
the study sections responsible for reviewing proposals do not have the
expertise to evaluate multidisciplinary projects, that young researchers cannot
compete, and that the practice of allowing applicants to revise and resubmit
proposals results in what amounts to experimental design by committee.
NIH has tacitly acknowledged
its peer review system does not reward innovation by creating the four new
grant programs with the explicit mandate to fund what it terms "high
risk-high reward" research (see "Risk-Reward at NIH").
However, the FY12 budget
allocates just $196.3M for these awards - a drop in the bucket compared to the
$16.5 billion total allocated to research project grants.
Next year NIH will provide at
most $15 million for Director's Transformative Research Awards and will award
up to seven Pioneer Awards. It expects to grant at least 33 New Innovator
Back to School argues these numbers
should be bigger. For example, expanding the four programs to 5% of the total
research project grant budget would move $825 million toward research that
promises innovation, and still is only a dollop of money compared to the
potential societal reward.
But these carve-outs are not
all that is needed. They must be accompanied by fundamental changes to the
application and peer review system - even if such changes may lead to reduced
funding for safer projects that would be more likely to provide solid, if not
Back to School argues that
research proposals should be cut to five from 12 pages, and there should be no
requirement for preliminary data.
In 2009, the maximum length of a research proposal was cut
from 25 to 12 pages. "It became apparent that the only way to keep
reviewers from focusing on the experimental details was not to have them in the
application," said Keith Yamamoto, vice chancellor for research at the University
of California, San Francisco and co-chair of an external advisory
committee convened in 2007-08 to advise the NIH on peer review reform.
He favors a seven-page limit.
But five is already the limit for the NIH Director's Pioneer Awards.
Back to School would go on to
decree that preliminary data should not be required for new R01 applications.
It is reasonable to assume that reviewers will still look for preliminary data
to support the feasibility of grant applications, but NIH can begin to change
this mentality by explicitly instructing reviewers that these are not required,
as it does for its subset of Director's awards.
Better still would be to
disallow preliminary data for Director's awards. Truly innovative ideas that
would not be funded by any other mechanism by definition should not be
validated with preliminary results. Permitting "optional" preliminary
data simply provides an excuse for the peer review process to play it safe and
flies in the face of the spirit of the award.
Again, ERC validates the idea.
It has adopted a funding scheme that aims to promote "frontier research"
and does not require any preliminary data - regardless of the career stage of
Without a requirement for
preliminary data to support feasibility, more projects selected for funding may
fail, and first-time renewal rates would decline. However, these tradeoffs are
worth making if they result in funding more innovative research projects.
Eliminating the requirement for
preliminary data also would enable skilled young investigators whose projects
fail to more quickly move on to new avenues of research.
Removing the preliminary data
crutch also would force NIH study sections to re-evaluate how they judge the
feasibility of novel experimental approaches and lines of research.
Fundamental changes also must
be made to the makeup of study sections to adapt to the increasingly
multidisciplinary nature of applications and to further encourage participation
by top investigators.
NIH currently recruits
technical specialists into individual study sections as ad hoc
reviewers. For example, if the tumor microenvironment section were reviewing an
application that uses a new microscopy technique, a specialist in that
technology could be added to the study section. But instead of reviewing only
the application involving that technology, the specialist, who may not have
extensive knowledge of the tumor microenvironment, would participate in the
discussion and scoring of all of the applications presented at the meeting.
This unnecessarily bloats the
size of study sections and is an unnecessary burden for specialists, who may be
more willing to volunteer their time if their expertise were more efficiently
For select multidisciplinary
applications, including for SBIR and Director's Transformative Grants, NIH
piloted a two-stage process to address this concern. In these pilots technical
merit was first assessed by specialist reviewers who provide a written
critique, but not a score. This was then followed by an in-person meeting of
topical experts to discuss the overall impact and significance of the science
and score the applications.
Back to School would ask why
the pilot has not been expanded to traditional R01 applications in select study
sections as a first step toward expanding it throughout the NIH peer review
This approach would ensure that
the most appropriate experts in rapidly developing technology contribute to the
review process, even if they don't have expertise in the particular field of
study being discussed.
It also would free study
sections to spend more time discussing the innovation and significance of grant
applications in a given area of biology, which is where their expertise
primarily lies and where their time is better spent.
While the peer-review system
provides the best system for the large-scale evaluation of scientific
proposals, Back to School also supports complementing the system with a second
model that selects individual researchers with high potential, and then gives
them sufficient funding to follow their noses for 5-7 years.
Long-term support allows a
scientist's work to diverge into unexpected avenues. It is also a way for
countries that do not have a long-standing tradition of excellence in
biomedical science to begin to build one.
This system has been highly successful at institutions such as
Howard Hughes, the Wellcome Trust and the National
Institute of Biological Sciences (NIBS) in Beijing (see "People
Over Projects," A11).
Such a model is not scalable to
the size of NIH. However, NIH should do more to identify exceptional
investigators and give them the trust and funding to pursue independent lines
of innovative research.
Along this line, NIH has
experimented with awards that emphasize the qualifications of the investigator
more than a traditional R01 would, but it needs to set aside a larger portion
of its budget for this purpose and explicitly fund the investigator, not the
The Director's Pioneer Award is
on the right track. It was established in 2004 to "support individual
scientists of exceptional creativity who propose pioneering approaches to major
challenges in biomedical and behavioral research."
However, the program is grossly
underfunded, having issued a total of $10.4 million in 13 grants in FY11. NIH
expects to hand out "at least 7" awards in 2013.
The agency's Method to Extend
Research in Time (MERIT) award also could be restructured to provide support to
individual investigators to pursue breakthroughs. Currently, the five-year award
serves as a prize that continues to support research that is in little danger
of losing funding.
MERIT is given by individual
NIH institutes to top experienced investigators in lieu of an R01 that is up
for renewal. The prize is intended to allow a PI to pursue more innovative or
risky work by providing temporary relief from competitive grant renewal. In
2007, MERIT awards accounted for about 3% of R01 grants.
However, last year the National
Heart, Lung, and Blood Institute (NHLBI) stopped participating in the
program because "much of the work funded by the MERIT program, while
highly meritorious, has not been especially 'high impact.'"
The program should be
restructured as an additional source of funds available to excellent
investigators who would apply on the strength of their past research
accomplishments. These investigators would then be free to pursue innovative
lines of research of their choosing.
Howard Hughes provides a model
with the selection criteria it uses to judge the quality of candidates up for
award renewal. According to CSO Jack Dixon, one is to apply the "subtraction
test," which asks: "If you were not there, would the field be worse
A much greater proportion of
public funds should be used for research, not for administrative overhead and
facilities. When tools and facilities are needed, public money should be spent
whenever possible on large-scale resources that many can use.
In the age of austerity, it is
no longer acceptable - if it ever was - for universities and research
institutes to skim an average of 27% off the top of grants funded with public
Nobody would donate money to a
charity he or she knew was spending 27% of donations on overhead. And if the
public knew that was the case with research funds, that wouldn't fly either.
In the current U.S. system,
overhead charges are determined from a base that consists of a project's direct
costs. Direct costs include salaries for investigators, technicians, postdocs
and other staff working on the project; reagents and other supplies; and
equipment. Direct costs also may include tuition and stipends for graduate
students working on a project.
Indirect costs, which are
intended to cover the operating and administrative costs of labs, are most
typically calculated as a percentage of direct costs.
This creates perverse
incentives for the universities, including cases in which universities actually
are not paying the investigator, because pushing salaries into a grant's direct
costs also bumps up the overhead charge.
These effects are illustrated
both by anecdotes and by data showing that university capital spending on
laboratory space tripled in response to the doubling of NIH's budget in
anticipation that the cost of their operation would be covered by public money.
Peter Ho, a founder and president of China's BeiGene
Ltd., told BioCentury that when he was first starting his career in big
pharma, there was no question research buildings and laboratories in industry
were newer and better designed than facilities in even fine institutions.
Now, he says, when he visits
top-tier institutions, their labs are not just as good as industry's - they're
are really not doing themselves a favor by charging exorbitant overhead,"
he said. "If you look at some of these buildings, do you really need to
spend that money building temples to research? Maybe you can spend that money
in other ways. Maybe more faculty get funding and do more research."
How much should overhead be
ERC is making it work with
less. Overhead in its grants is calculated as a flat 20% of eligible direct
Horizon 2020, the research and
innovation program in the EU for 2014-20, which will succeed Framework Programme
7 (FP7), also has a proposed 20% flat rate for overhead.
Medicines Initiative, the public-private partnership of the European
Commission and the European Federation of Pharmaceutical Industries and
Assocations (EFPIA), offers two options. Organizations that are able to
calculate actual indirect per-project costs can receive full reimbursement for
that amount. Organizations that are not able to do so - which is most of them -
If Congress were to cap the
amount of overhead that can be included in an NIH research grant at 20% of
direct costs, or 17% of the grant's total, that would save $1.7 billion based
on the FY12 allocation of $16.5 billion and the current average overhead, which
is 27% of total grant funds.
technologies that are necessary to conduct basic research must be paid for, and
Back to School would argue this can be a particularly good use of public money
when it is used to fund large-scale resources that many can use.
For example, Brandeis
University has a nuclear magnetic resonance facility that may be used
by any NIH-funded researcher, especially those in New England.
Another example is the Broad
Institute of MIT and Harvard's Chemical Biology Program, a high
throughput screening facility that can be used by the public research
In New York, 11 institutes have banded together to build the New
York Genome Center, a large-scale genome sequencing facility that will
provide a dedicated resource for DNA sequencing and bioinformatics and is
intended to facilitate collaborations between institutes.
Finally, Back to School also
agrees with arguments put forth in a 2010 editorial by Bruce Alberts,
editor-in-chief of Science, that grantee institutions actually need to
have skin in the game.
According to Alberts, NIH
should require institutions to pay at least half of a PI's salary.
"A new NIH policy must
make it unambiguously clear that expansion through laboratory building
construction requires a substantial, nonreimbursable, long-term commitment of
resources, including 'hard-money' faculty support, by any institution that
wants to increase its facilities and research staff," he wrote.
Leveraging human capital
Training has to be revamped
to reduce money that now is spent to create a surfeit of scientists, and to
allow the best of them to conduct independent research earlier in their
An inevitable consequence of
rebasing is that university research programs will shrink. But Back to School
argues that the science establishment, which is producing many more postdocs
than can find jobs in their fields, is due for a right-sizing.
NIH is by far the largest
funder of science training in the world, and thus provides the object example.
For starters, the U.S. is
demonstrably cranking out many more Ph.D.s than the system can support.
It is not in the public interest
for NIH to fund training for a growing and significant fraction of individuals
who ultimately have no career path in the biomedical enterprise. Nor is it in
the public interest to continue to use dear dollars on a training system that
prevents talented young researchers from making independent contributions.
Between 2000 and 2010, the
number of Ph.D. graduates in the biological or biomedical sciences in the U.S.
increased by 38% from 5,853 to 8,052, according to survey data from the National
Science Foundation (NSF). Yet the proportion of life sciences Ph.D.s
employed in occupations that are closely related to their field dropped to 59%
in 2008 from 70% in 1997.
In addition, Ph.D.s can go on
to two or three postdocs. These are intended to be temporary positions that
provide additional training, but they more closely resemble indentured
servitude lasting until or unless independent research positions can be
obtained. Only then can scientists apply for and receive a major independent
grant, which Back to School already has noted does not happen until an average
age of 42 in the U.S.
According to NIH's Biomedical
Research Workforce Working Group, the NSF survey showed a "significant
number" of postdocs remain in these positions 5-8 years - hardly
Back in 2005, the National
Academy of Sciences argued no postdoc should receive funding for more
than five years. This limit would benefit the ecosystem by pushing scientists
into independent exploration of more novel ideas sooner. And it would force
individuals with no academic career prospects to find work where they can be
On this latter point, NIH
should insist that the graduate programs it pays for educate students about
careers outside of academia.
"Less than half of the
people trained in Ph.D. programs in biomedicine end up in tenure track
positions, and many more of them expect that will be the outcome," Collins
told BioCentury. He said training programs should give students and postdocs
the opportunity to sample different career options, and added universities
should no longer refer to these opportunities as "alternative careers."
"It is not necessarily the
case that being a faculty member at a university is the highest, boldest of all
options," Collins said.
Some science funders have
launched initiatives to help accelerate the transition from mentored postdoc to
independent investigator, and to allow some Ph.D.s to go straight from graduate
school to independent research without a postdoc. But these initiatives are too
small to change the overall demographics.
In FY2012, NIH's allocation for
training totals $777.8 million. The agency thus has the power to dramatically
reshape the training of scientists from around the globe by changing the way it
allocates funding and by demanding that the training programs it pays for
prepare students for multiple career paths.
It does have two such programs
funded through the NIH Common Fund.
The Pathway to Independence
award, which was established in 2007, provides two years of mentored funding to
postdocs followed by three years of independent funding contingent on securing
a faculty position. In 2011 there were 180 awards funded - a 22% success rate
However, postdocs are eligible
to apply for the award through their fifth year of support, which leads to an
unnecessary extension of their mentored training and unfairly pits them against
the postdocs with little experience whom the award is intended to nurture.
The Biomedical Research
Workforce Working Group has recommended cutting back eligibility from
fifth-year to third-year postdocs, along with a doubling of the number of
A second NIH program, launched
in 2011, is the Director's Early Independence award. It allows exceptional
Ph.D. and M.D. candidates to forgo a postdoc and immediately begin independent
research. The award provides five years of funding and is available within the
first year after a candidate receives his or her terminal degree.
This program is modeled after prestigious and competitive
fellows programs funded by the Whitehead
Institute for Biomedical Research and UCSF.
NIH expects to award 10 early
independence grants in 2013. Back to School finds it hard to believe there aren't
more than 10 graduates ready to be given the chance to conduct independent
research. If the number of awards were quadrupled to 40, it still would amount
to only about 0.5% of the current number of graduates each year.
Initiatives that help speed the
transition of Ph.D.s and postdocs to independence are necessary, but they do
not address the reality that it is more difficult for new independent
investigators to receive grant funding in a system that requires them to compete
with established researchers.
Howard Hughes' Dixon argues it
is particularly important to fund new independent investigators. "This is
when you are really at your best, and you don't want to burn these young people
out - you want to give them the opportunity," he said.
Howard Hughes is one of several
institutes inside and outside the U.S. that have established grant
programs specifically targeted to the career stage of the investigator.
ERC has separate grant programs
for independent scientists who are 2-7, 7-12 or any number of years past
completion of their Ph.D. These programs are called Starting Grants,
Consolidator Grants and Advanced Grants.
"In a competitive granting
scheme, you have to compare like with like," said Anna Tramontano, a
member of the ERC Scientific Council.
One reason, she said, is that
one would expect scientists at different career stages to be capable of
different kinds of research. For example, a more experienced researcher may be
better able to manage a project requiring a large group. In contrast, newly
minted investigators don't usually have a group and would be likely to propose
different kinds of projects.
NIH's approach has been to
identify and label grant applications from new or early stage investigators,
discuss and score them separately, and then require that individual institutes
lower the cutoff hurdle for funding them. New investigators are defined as
those who have never before received an R01 grant. Early stage investigators
are a subset of new investigators who graduated up to 10 years ago.
For example, in FY12 NIAID
funded all R01 grants that scored in the 10th percentile for established
investigators, but extended that cutoff to the 14th percentile for new
Critics would argue this policy
supports young investigators at the expense of higher quality science. However,
there are legitimate reasons why young investigators may obtain lower grant
scores that have little to do with their science, including grantsmanship by
seasoned PIs, lack of resources to obtain preliminary data, and a less
developed history of accomplishments.
Scaling up collaboration
The adaptation to austerity
also should result in more collaboration, not only on the relatively small
scale between and among investigators and institutions, but also on a much
larger scale between governments.
In 2011, Back to School mined
this theme of "Innovation & Collaboration." It argued the
biopharma industry was "busy restructuring for the future," and that
better engines of value creation would result "only if truly fresh
thinking is allowed to replace old expectations and habits."
Back to School argued this will
require "an already heavily partnered industry to be even more
broad-minded about how collaborations must be at the center of value creation"
(see BioCentury, Sept. 5, 2011).
The age of austerity will
impose the same imperative on the publicly funded research enterprise.
There are no obvious mechanisms
for forcing global research collaborations between institutions or between
governments. But the prospect of starvation will be a mighty motivator for
finding ways to pool resources and expertise on problems that could benefit
from the diversity of scientific disciplines and approaches that are a
precondition for solving today's most compelling scientific questions.
For example, progress in many
areas will be contingent on skill in managing big data - skills that life
sciences academics and industry lack.
Weizmann Institute of Science has done particularly well, although that
is in large part due to the institute's small size and the fact that scientists
at the Weizmann spend so much time together.
The institute comprises five
faculties: biology; biochemistry; chemistry; physics; and mathematics and
"We have 250 active PIs,
and the science buildings are clustered together, so we are all physically very
close together," said Irit Sagi, the Maurizio Pontecorvo professorial
chair in the department of structural biology. She noted many of the researchers
live on campus.
"All this informal
interaction leads to fruitful collaborations and unexpected collaborations. It's
not something like the institute directs these collaborations; it's very
natural. Scientists love their work, and when we get together, after five
minutes we talk science," she told BioCentury (see "A Matter of
While that hot house
environment would be difficult to replicate, and probably is impossible to
replicate on a large scale, the Weizmann still provides lessons for other
science funders about what kinds of collaborations can work well.
"Usually a good
collaboration is when two or three collaborators come from absolutely different
and distinct disciplines, and each is able to bring a specific component to the
project," Sagi said.
That thinking applies to
industry-academia collaborations as well. While these have been rapidly
increasing in number in recent years, Back to School argues for more.
"I would hate to see NIH take money away from basic
research because NIH is not good at applied and translational research. That is
the role of industry or industry-academic partnerships," said Douglas
Williams, EVP of R&D at Biogen
Biogen Idec has recently
announced its participation in a handful of research consortia and
collaborations. The company is providing funding to support academic
investigators in basic research, but expects its own role will be to add value
downstream via applied experiments.
In two of these - an amyotrophic lateral sclerosis (ALS)
consortium with the Hudson
Alpha Institute for Biotechnology; Duke
University; the University
of Massachusetts Medical School and Columbia
University Medical Center; and the human interactome project with
Harvard - the academic institutions will own resulting IP and are expected to
publish the results (see BioCentury, July 2 & SciBX: Science-Business
eXchange, July 26).
are another area where greater efforts are needed.
For example, One
Mind for Research aims to coordinate global multidisciplinary expertise
in the neuroscience space. Launched last year, One Mind is a program sponsored
by the International
Mental Health Research Organization focused on precompetitive
neuroscience research, education and awareness-building programs. The program
involves a global coalition of neuroscientists, advocates, policy makers and
Pharmaceuticals Inc. unit has committed $2 million in cash and $1 million in
matching donations to the program.
The program's first initiative is focused on creating a "knowledge
integration network" for research on traumatic brain injury. It includes a
partnership with the International
Neuroinformatics Coordinating Facility to create a system for
multiple-source data sharing from research efforts around the world.
The initiative's many collaborators also include data,
informatics and analytics organizations such as the Neuroscience Information
Data Corp. and GNS
Healthcare Inc.; research organizations such as UCSF, the University
of Michigan, SAGE
Bionetworks and NIH; health information-sharing website PatientsLikeMe
Inc.; and therapeutic and diagnostic companies such as Eli
Lilly and Co. and General
Electric Co.'s GE Healthcare unit.
Another international initiative is led by the Structural
Genomics Consortium, which is supported by the Canadian government, the
Wellcome Trust, and six pharmaceutical companies. SGC works with partners in
the U.S., the U.K., France, and Canada to determine crystal structures and
develop chemical probes against human proteins of biomedical importance.
In July, an SGC-GlaxoSmithKline
plc team published the first potent and selective histone demethylase
inhibitor (see SciBX: Science Business eXchange, Aug. 9).
also can help develop and strengthen expertise in countries that are trying to
build a research base.
In Brazil, the Sao
Paulo Research Foundation (FAPESP) has issued calls for proposals that
provide funding to joint teams of researchers from local institutions working with
international collaborators. FAPESP Scientific Director Carlos Henrique de
Brito Cruz told BioCentury the initiative began in 2006 to fund the
international exchange of researchers and now includes the co-funding of joint
FAPESP has relationships with organizations including Research
Councils UK, the French
National Research Agency (ANR), and the German
Research Foundation (DFG).
Adopting Back to School's
proposals will not fix every problem that threatens the continued productivity
of the global research enterprise. Nor does Back to School have a corner on the
market for solutions to the problems discussed in this essay. Other ideas
should be put on the table.
No matter what the source, Back
to School argues the best proposals would act synergistically to reduce waste
in the system; provide greater rewards to the most innovative projects and
investigators; expand the pool of ideas; and more closely tie the efforts of
basic research to the desired outcome of medical breakthroughs.
For example, reforming training
and peer review in parallel should together help ensure the individuals and
projects with the greatest potential to transform the treatment of disease
receive the funding they need.
Reforming peer review also
would increase the likelihood that multidisciplinary projects could receive
funding and thus also would promote the kind of collaboration that can lead to
quantum leaps in knowledge.
Making meaningful communication
between product developers and basic researchers a prerequisite for funding
would speed the solution to logjams where therapeutics are urgently needed in
areas of unmet need - particularly where diseases are poorly understood - and
make it much easier to assess and measure the productivity of basic research
Reducing the funding for
overhead that goes to individual institutions while investing in more large
scale resources that can be shared ought to not only reduce wasteful costs, but
also promote collaboration.
In turn, promoting larger-scale
collaboration at the institute and even government level should not only help
to move the science forward faster, but also should help reduce waste in the
form of redundant experiments - and especially redundant failures.
Entrenched interests will fight
these reforms with politically charged warnings about the erosion of global
competitiveness and the loss of high quality jobs. But global austerity will not
be denied. A leaner system of training and research, one that identifies and
nurtures the very best, is the only way to weather the belt tightening that is
already upon us.
It also will put the research
community in the best position to ask for and receive more funding when the
coffers open again.
Finally, as all this
transpires, the social value of research will only be realized if it is
translated from bench to bedside. This will be industry's job, and it will have
to live up to this obligation.
The 20th Back to School
Commentary is a collaborative work led this year by BioCentury Editor Susan
Schaeffer and co-writers Washington Editor Steve Usdin and Senior Writer Chris
Cain. Data were developed by Research Director Walter Yang and News Editor
Meredith Durkin. The package was edited by Chairman & Editor-in-Chief Karen
Bernstein and President & CEO David Flores.
of American Medical Colleges (AAMC), Washington, D.C.
Ltd., Beijing, China
Idec Inc. (NASDAQ:BIIB), Weston, Mass.
Industry Organization (BIO), Washington, D.C.
University, Waltham, Mass.
Biosciences National Laboratory, Sao Paulo, Brazil
Institute of MIT and Harvard, Cambridge, Mass.
University, New York, N.Y.
University, Durham, N.C.
Lilly and Co. (NYSE:LLY), Indianapolis, Ind.
Commission (EC), Brussels, Belgium
Federation of Pharmaceutical Industries and Associations (EFPIA),
Research Council (ERC), Brussels, Belgium
National Research Agency (ANR), Paris, France
Electric Co. (NYSE:GE), Fairfield, Conn.
State University, Atlanta, Ga.
Research Foundation (DFG), Bonn, Germany
plc (LSE:GSK; NYSE:GSK), London, U.K.
Healthcare Inc., Cambridge, Mass.
Medical School, Boston, Mass.
Hughes Medical Institute, Chevy Chase, Md.
Alpha Institute for Biotechnology, Huntsville, Ala.
Medicines Initiative (IMI), Brussels, Belgium
of Medicine (IOM), Washington, D.C.
Pasteur Korea, Seoul, South Korea
Mental Health Research Organization, Rutherford, Calif.
Neuroinformatics Coordinating Facility, Stockholm, Sweden
& Johnson (NYSE:JNJ), New Brunswick, N.J.
Academy of Sciences (NAS), Washington, D.C.
Cancer Institute (NCI), Bethesda, Md.
Center for Advancing Translational Sciences (NCATS), Bethesda, Md.
Heart, Lung, and Blood Institute (NHLBI), Bethesda, Md.
Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Md.
Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Md.
Institute of Biological Sciences (NIBS), Beijing, China
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
Institute on Drug Abuse (NIDA), Bethesda, Md.
Institute of Mental Health (NIMH), Bethesda, Md.
Institutes of Health (NIH), Bethesda, Md.
Research Council (NRC), Washington, D.C.
Science Foundation (NSF), Arlington, Va.
York Genome Center, New York, N.Y.
Mind for Research, Rutherford, Calif.
Inc., Cambridge, Mass.
Data Corp., Newton, Mass.
Councils UK, Swindon, U.K.
Bionetworks, Seattle, Wash.
Paulo Research Foundation (FAPESP), Sao Paolo, Brazil
National Research Foundation, Singapore
Genomics Consortium, Oxford, U.K.
of California, San Francisco (UCSF), San Francisco, Calif.
of Massachusetts Medical School, Worcester, Mass.
of Michigan, Ann Arbor, Mich.
Pharmaceuticals Inc. (NASDAQ:VRTX), Cambridge, Mass.
Weizmann Institute of Science, Rehovot, Israel
Trust, London, U.K.
Institute for Biomedical Research, Cambridge, Mass.