Drug Discovery and Development:
A Complex Team Sport
By Jill U. Adams
United States
7 March 2008
Joe Bolen
Academic drug
discovery is taking
on a whole new
character now, with
technology and new
partnerships between
academia and
industry and disease
institutes and the
government.
To succeed in drug discovery today, you need to be a jack of many
trades and a master of (at least) one. Depth and breadth. Both are
required of scientists working on making new drugs. So say managers
in big pharma, biotech, and government programs in drug discovery and
development.
“When you’re working toward a Ph.D., you’re focused like a laser on
whatever your area of work is,” says Joe Bolen, the chief scientific
officer at Millennium Pharmaceuticals in Cambridge, Massachusetts.
While such focus may suit the current educational paradigm of doing
serious benchwork and publishing, Bolen says, “You can get so focused
that you lose track of everything else. And that’s not what we’re looking
for. We want experts in their field, but we want people who appreciate
what’s going on in the broader area.”
The path to new drugs is long and costly, fraught with potholes and
littered with failures. As compound libraries flood the known chemical
space (and analytic capacity), new drugs on the market have slowed
to a trickle. “Everything has gotten much more complex. People say the so-called easy things have been
done,” says Bolen, and what’s left is really hard. “I think that’s true to some extent.”
As new models of drug discovery are developed, those working in the field say it’s a time of exciting
science, with nontraditional targets to be investigated, new technologies to be harnessed, and better
ways to process reams of information to be created. Drug discovery and development, whether housed in
private companies or supported by public funds, is goal-oriented science, where teams of people work to
solve specific disease issues. This can be a good thing for those who like solving problems, who thrive on
the steep part of a learning curve, and who gain satisfaction from a feel-good contribution to society.
Hiring for preclinical drug discovery remains strong in the pharmaceutical industry, says
Rich Pennock of Kelly Scientific Resources, a human resources firm. “The pipeline is so important to the
health of these companies.” Hiring in biotechnology is more cyclical, he says, tending to follow the financial
markets, as young companies are more dependent on outside capital to invest in new resources.
Interdisciplinary Teamwork
Drug discovery runs the gamut of disciplines from synthetic organic chemistry to molecular and cellular
biology, from in vitro to in vivo pharmacology and toxicology, from basic science to clinical testing.
Expertise in engineering, computer science, and bioinformatics also is required to help integrate new
advances in technologies such as high throughput screening of compounds and in silico modeling.
No one scientist is trained in all those areas; rather, project teams
are standard operating procedure in the pharmaceutical industry.
In addition to chemistry, biology, and associated subdisciplines,
the process “requires Ph.D.-level people in math and statistics, as
well as engineers, automation specialists, computer specialists, and
physicists,” says Bolen, all of which are represented at Millennium.
“The list just goes on and on. It’s an incredible group that has to come
together to make new medicines.”
Lois Lehman-McKeeman is a toxicologist at Bristol-Myers Squibb
in Princeton, New Jersey, but she works closely with biologists and
chemists in discovery. The toxicology group works to predict adverse
effects and tries to assess them early in the discovery process. In
addition to this proactive strategy, her group has to react when
toxicities arise and investigate “whether that’s related to the chemistry
that we’re working with, or whether that’s a function of the target that
we’re manipulating,” she says. “The fun part of the pharmaceutical
industry is that all of those parts have to come together. Being able to
work together is important.”
“Once we solve a
problem, we move on.”
—Lois Lehman-McKeeman
The team approach to drug discovery and development differs from
the stereotype of an academic scientist working independently on
his or her own project. “You really do work in groups,” says Lehman-McKeeman, which comes with
advantages. “You learn from each other―that helps your own professional growth―and eventually
you get to the end.” Learning new things is a plus for many people, she continues. “The science
behind discovering a drug is as intellectually challenging as any academic problem there is. We’ve got
to have the best science underlying everything that we do. It is intellectually demanding. It requires
continuous learning and continuous growth.”
Bolen agrees. “What we’ve rediscovered is that making new medicines is the most complex team
sport on the face of the earth,” he says.
Project teams exist outside of industry as well. At the US NIH Chemical Genomics Center (NCGC) in
Rockville, Maryland, engineers, informaticists, biologists, and chemists work together, and deputy
director Jim Inglese specifically looks for people who are willing
to do that. “We have people who know what their strengths and
weaknesses are and are happy to work with people who complement
those,” he says.
Part of the NIH Roadmap’s Molecular Libraries Initiative, the NCGC
is one of a network of screening centers, which provide access to
a large chemical library, expertise in developing assays for high
throughput screening, and the subsequent synthetic chemistry to
develop the active compounds.
Jim Inglese and one of his
NCGC postdoc trainees,
Dr. Natasha Thorne
Most of the people at the NCGC are excited by technology and
process, says Inglese. “We really are committed to making the
whole paradigm of early drug discovery work better. How do you do
all that efficiently when the target or assay is different every time?
It’s always different and it’s always challenging. The perk is being
able to work on a different type of biologic system every couple of
days or weeks.”
New Models
The government effort is all about integrating the biology from academic
labs with the NCGC’s screening and chemistry resources. Postdoctoral
fellows there learn the technological aspects of scaling up an assay
they’ve developed with an investigator on the NIH campus. They also
learn the informatics aspect of identifying promising compounds and
work with chemists “to do the optimization of a compound to improve its
potency or solubility or selectivity,” says Inglese. “That’s a whole chunk
of the drug discovery process.”
It not only prepares postdoctoral fellows for a career in industry, but also
for drug discovery efforts in government and academia. “Academic drug
discovery is taking on a whole new character now, with technology and
new partnerships between academia and industry and disease institutes
and the government,” Inglese says.
Frank Vocci
In addition to the work done at the NCGC, other elements in the
Roadmap’s theme of “new pathways to discovery” include biological
pathways, structural biology, bioinformatics, and nanomedicine. With these initiatives, the NIH aspires to
provide a toolbox for medical research to take advantage of the human genome sequence and the
latest progress in molecular and cell biology for the development of new therapies.
Other institutes within the NIH have medication development programs. “We take in compounds and
evaluate them in various screens,” says Frank Vocci, who directs the division of pharmacotherapies at
the National Institute on Drug Abuse (NIDA). Groups in chemistry, toxicology, regulatory affairs, and
clinical research make up the broad spectrum of expertise within the division. It’s a service to external
researchers and companies―they submit compounds and receive confidential reports in return. But NIDA
also hopes to stimulate progress in filling the pipeline with lead compounds, especially in a therapeutic
area like drug abuse that is not well served by industry. Progressing to drug development typically
involves working in joint ventures with industry and academia, says Vocci.
These innovative government programs are filling a need for rare diseases and unmet targets, but they
also show that alternative models of drug discovery and development are possible. Industry is changing as
well, says Jim Barrett, an industry veteran now at Drexel University College of Medicine in Philadelphia.
“Industry is going through some fairly sophisticated attempts to incorporate new technologies to the drug
discovery process―things like expanded chemical libraries, very high throughput screening, combinatorial
chemistry, and then the whole genome initiative―the promise of genetics and genetic therapies and new
targets,” he says. “I think we’re still sitting on the edge of real breakthrough medicines and haven’t yet
coupled all of those new technologies and techniques together with the
emerging science.”
Peter Schafer, who directs the biology group at Celgene in Summit,
New Jersey, puts it another way. “I think we’re entering an era when one
has to think outside that box, which is very difficult, because it means
that you have to have the humility to admit that you don’t understand
everything that’s happening in a disease and a pathway.”
Goal-Oriented Problem-Solving
Jerry Skotnicki
Keeping the long-term goals in sight is crucial to drug discovery and
development, whether the setting is academic or industrial. “I think
stamina is a very important aspect,” says Jerry Skotnicki, who directs
chemical and screening science at Wyeth in Pearl River, New York.
“I don’t mean the ability to trudge, but to sustain one’s effort and
dedication, because sometimes things don’t work out as quickly or as
clearly as one would like.”
Staying focused is another aspect. “Scientists spend a lot of time
thinking about tangential questions, that are academically interesting
but not so important for getting a drug approved,” says Schafer. “To
accumulate the appropriate data to put into a regulatory submission,
you just need to focus on the required information,” he says.
Lehman-McKeeman calls it doing the last experiment first. “It’s the way
we have to think. What is the critical question? And how do we get that
answer?”
Goal-oriented science also requires a willingness to be flexible. “Once
we solve a problem, we move on―as opposed to continuing to drill
deeper down into an academic question,” says Lehman-McKeeman. The
fact that there’s a clear resolution can cut both ways, rewarding when you
have a drug and frustrating when you don’t.
Peter Schafer
Indeed, project team goals in industry are often of the go/no-go variety, where a weak project might get
scrapped at short notice and the researchers need to be able to let go and move on. A similar dynamic is
present in the fast-paced lab at the NCGC, says Inglese, where timelines are relatively short.
But with flexibility comes opportunity―the opportunity for researchers to continually learn new things and
to push their knowledge base into new areas. “Even within the confines of a company, there will always be
so many possibilities,” says Schafer. Companies are looking for new angles of disease, new drug targets.
“We’re constantly challenged to look outside of what we’re doing, because the best opportunity might be
two steps removed from where you’re currently working.”
Importance of Education
Most scientists in drug discovery and development today have learned what they need to know on the
job. NCGC’s Inglese has compound screening experience in both biotech and pharmaceutical companies.
NIDA’s Vocci has a regulatory background from more than a decade of work at the US Food and Drug
Administration. Drexel’s Barrett has a resume that includes an academic faculty position and research
and senior management experience in industrial settings from big and established (Wyeth) to small and
startup (Memory Pharmaceuticals).
Barrett now has returned to academia, starting an educational program in drug discovery and
development at Drexel. “To my knowledge, there is no such formal program that integrates the details,
complexity, and all of the nuances of drug discovery and development into the graduate education
program,” says Barrett, who hopes to ease the transition for students interested in an industrial career.
Making the most of the resources at Drexel and at other institutions in the greater Philadelphia area,
Barrett plans to grow the program into a minor or specialization for graduate students in the biomedical
sciences. Through the program and internship experience, students will be better prepared to start a
career in a biotechnology or pharmaceutical setting. “They’ll have had experience working in project
teams, experience in how you identify a target all the way through to preclinical evaluation and toxicology,
as well as marketing and postmarketing surveillance.”
Hard and Soft Skills
While such tertiary education may tip the balance in your favor, depth of knowledge in a specific scientific
area―whether it’s synthetic organic chemistry or molecular pharmacology―is one of the most important
things on your resume, say hiring managers.
“What I look for is someone with good bench skills, first and foremost,” says Celgene’s Schafer, because
someone has “to generate the work product.”
Beyond how you look on paper, how you present your work in person is key for Bristol-Myers Squibb’s
Lehman-McKeeman. “You cannot hide enthusiasm for what you do. Nor can you hide the fact that
something isn’t that interesting to you,” she says.
“Number one, you have to be passionate about what you do,” says Millennium’s Bolen. If you’re not, no
one else will be. “Number two, you have to have perspective,” he continues. “That perspective says that
what you’re doing is no more important than the guy or the gal in the lab next to you. Everybody’s work is
important.”
A certain breadth of experience is vital as well, because when you’re talking about industry, you’re talking
about teamwork. In addition to bringing your own skills and know-how to the project team table, you have
to appreciate and be curious about what the other team members have to offer.
“Communication is important, because in a mid-size company like Celgene, you wind up wearing
many different hats,” says Schafer. Drug discovery scientists may serve as the drug discovery group
representative on product development teams. When a change in clinical direction occurs, that person has
to convey the change back to drug discovery to work on a new set of data.
Another hat may be to provide scientific information to a company’s marketing group, “to help in the
messaging and to help describe to clinicians and sometimes even to investors what the features of the
product are and how it relates to efficacy and the disease,” says Schafer.
Says Wyeth’s Skotnicki, “The successful people are those who have collaborative skills, leadership
qualities, and a respect for people, coupled with the drive to get things accomplished.”
Jill U. Adams is a freelance writer living in upstate New York.
DOI: 10.1126/science.opms.r0800049
Bristol-Myers Squibb - www.bms.com
Celgene - www.celgene.com
Drexel University College of Medicine - www.drexelmed.edu
Kelly Scientific Resources - www.kellyscientific.com
Millennium Pharmaceuticals - www.mlnm.com
National Institute on Drug Abuse (NIDA) - www.nida.nih.gov
US Food and Drug Administration - www.fda.gov
US NIH Chemical Genomics Center (NCGC) - www.ncgc.nih.gov
Wyeth - www.wyeth.com
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