The drying drug pipeline and looming patent cliff, together with the ailing economy, has hit the drug discovery business hard, forcing the industry to lay off workers and rethink and restructure its research and development models. In the United States alone, the pharmaceutical industry has shed more than 20,000 jobs this year and, over the last decade, layoffs have surpassed 300,000, according to the outplacement services consulting firm Challenger, Gray & Christmas.

Will the industry recover? Probably -- in some form. The need for better health and treatment for disease isn't going away. It's early still, and far from obvious what shape the new pharmaceutical industry will take, but patterns are emerging that can help guide the career-related choices of aspiring pharma scientists. Science Careers spoke to scientists from several companies, big and small, seeking tips on where and how to seek scientific jobs in drug discovery and development. Their answer: Go small, but think big.

Shrinking revenues, shrinking companies

The most important change occurring in the industry is a shift away from the traditional "big pharma" model for drug development, in which research and development are concentrated inside such companies as Pfizer, Merck, and AstraZeneca. As industry giants lose patent rights on big-money drugs such as Lipitor and Plavix, they are looking to offset lost revenues by cutting costs and lowering exposure to the risks and expenses of drug discovery and development.

Also read “A Pharma Industry in Crisis” by Elisabeth Pain. For more coverage of careers in pharma, see our Content Collection.

One of the most important ways they're doing this is by, in effect, outsourcing early-stage research and development to smaller pharma and biotech companies. The result is more jobs at smaller companies -- especially biotech companies -- for innovative scientists, says Steven Braithwaite, senior vice president of drug discovery at Signum Biosciences, a 10-person biotech company located in Monmouth Junction, New Jersey. "I think there is more open opportunity in small biotech for people with an academic background," he says. "Innovative ideas are risky, and taking that [risk] out of big pharma is probably the future."


Courtesy of Steven Braithwaite
Steven Braithwaite

Braithwaite himself, who holds Ph.D.s in neuroscience and anatomy, is an example of the trend. He moved to Signum from a large pharmaceutical company because he wanted to be involved in riskier, more innovative projects. Another advantage: A smaller company allows him to be more involved in other aspects of the business besides research, he says. "You're not just part of a conveyer belt. You have to get involved in a whole range of techniques at the bench, but you also have to get involved in the business side, in the business thinking."

Gretchen Snyder, executive director for molecular neuropharmacology at the 25-person Intra-Cellular Therapies Inc. in New York City, agrees that job opportunities are shifting to smaller companies. "Smaller companies, I think, are in a position to provide some of the early-stage work that big pharma used to do in-house."


Courtesy of Gretchen Snyder
Gretchen Snyder

The poster child is Vertex Pharmaceuticals, a small company headquartered in Cambridge, Massachusetts. Launched in 1989, Vertex won FDA approval in May for a new drug for hepatitis C, which is expected to earn big money. The company, which already has R&D sites at several U.S. locations, as well as in Canada and the United Kingdom, grew by more than 30% -- from 1400 employees to about 1900 -- between early 2010 and September 2011. The company plans to add an additional 500 jobs through 2015 and is building a new headquarters in Boston, where it will relocate its Massachusetts workforce.

Will job growth in smaller companies offset losses in big pharma? Not likely, or not for a while. Vertex is in many ways an exception. Many smaller companies are finding it hard to finance their operations, says industry journalist Ed Silverman, who edits the Pharmalot blog. The global economic downturn has kept many start-ups on the ground, says Derek Lowe, author of the pharma-industry blog In the Pipeline. Still, “those that are financed for the moment to continue their work are going to hire people to do that research,” Silverman says. The bottom line: “The big drug-makers proportionally are doing more cutting back,” he adds.

Traditionally, job security hasn't been as good at smaller companies. As Josh Bloom, director of chemical and pharmaceutical sciences at the American Council on Science and Health in New York City, sees it, “the trouble is if you work for a place like that you lose two ways. If you’re not successful, the company goes out of business, and if you are successful, then the [bigger] company that maybe you’re partnered up with ... will buy you and then you lose your job then.” It makes sense to anticipate layoffs, by living and working in a place like the Boston area or the San Francisco Bay area with a lot of small companies, so “if you have to go to another company, you can do it without calling the moving trucks,” Lowe advises.

Michael Ehlers, chief science officer for neuroscience research at Pfizer, says that even big companies are moving toward something like a small-company model. Ehlers will head Pfizer's new neuroscience research division, stationed on the campus of the Massachusetts Institute of Technology in Cambridge, slated to open by summer 2013. "There's been a trend across the industry within large companies [to organize] around smaller, nimbler units," he says. "Within Pfizer neuroscience, we're clearly autonomous research units. I'd say we're moving toward a highly enabled biotech kind of structure where we have all the innovation of a more biotech setting."


Courtesy of Pfizer
Michael Ehlers

Tailor-made

Another trend in the industry is a shift away from small-molecule/big-market solutions and toward biologically-derived drugs for targeted populations. As new blockbuster drugs for large, general populations become harder to find -- and as scientific advances make new biological approaches possible -- prospective drugs that target smaller populations are getting more attention, says Dale Edgar, a research fellow and chief scientist of a sleep disorders research unit at Eli Lilly, based in Guildford, U.K.

Scientists involved in such projects need to be able to determine why a drug works very well in some patients but fails completely in others. So, scientists seeking work in the pharmaceutical industry benefit, both Edgar and Snyder say, from a deep knowledge of biogenetics, computational biology, and bioinformatics. "A genetics background is extremely important for understanding how drugs work as tailored therapeutics, why one drug might work in one person but fail in another," Edgar says.

Genetics is also important for understanding how research scales up -- or fails to -- and translates from animal models to humans and among different human populations, says Henry Bryant, a research fellow at Lilly Research Laboratories in Indianapolis. "Right now, one of the biggest areas of failure is in phase II trials, when you get to those places where you're looking for efficacy and you suddenly discover that the compound that worked great in your animal model doesn't do much in humans," he says. "That's a long experiment to find a failure. So the more that we can understand the human validation of our targets and perhaps even build model systems that take advantage of human biology," the better off we'll be, he says.

Be fresh, broad, and innovative

Small companies are looking for creative-minded scientists who aren't afraid to involve themselves in several areas of the company, Snyder and Braithwaite say. Small companies with shoestring staffs can't afford to allow their scientists to limit themselves to pet research interests. "Being flexible and trying to expose yourself to as many types of techniques as possible in your training really sets you up in a good place in terms of being in a small company, because the projects, the targets, the approaches all change," Snyder says. Braithwaite adds, "small biotech is really fueled by innovation, … so it's very important to be getting experience in techniques that are really the cutting edge of science and not just the old standard techniques."

Postdocs and Ph.D. students, Braithwaite continues, should do everything possible to establish reputations as innovative thinkers with fresh ideas. When working on a dissertation or a project as a postdoc, "you really need to take the lead and you need to find the interesting, novel aspects of it. Don't just go for the low-level types of experiments; go for something that really is innovative. I think you have to think very early in your scientific career, in your Ph.D., in your postdoc, about doing studies that are worthy of Science and not just worthy of low-level journals. You've really got to take those risks."

Meeting academia halfway

Another place where scientists may find opportunities is in academic labs. “There are a lot of companies that are trying to have closer ties with academic labs and many very good, high-quality academic centers now have the same equipment and research abilities. They’re looking at the same types of pharmacological targets that maybe only used to be pursued at a drug company in the past,” says Philip Mayer, president of the American Association of Pharmaceutical Scientists in Arlington, Virginia. In the United States, Mayer counts a dozen universities -- including the universities of Texas, Kansas, and Kentucky -- that “are interested in providing compounds for industry and taking that compound even into clinical studies if they can.” While discovery-type positions tend to be filled by postdocs and graduate students, people who perform drug formulation research and contract manufacturing at places like the universities of Kentucky, Iowa, and Maryland often take permanent positions as group leaders, supervisors, or technicians, Mayer adds.

Outside the United States, the University of Toronto in Canada and the University of Oxford in the United Kingdom have been working to solve protein structures to identify drug targets as part of the Structural Genomics Consortium (SGC), which is partly funded by GlaxoSmithKline, Novartis, Lilly, and Pfizer, writes Sarah Jones, education and skills manager at the Association of the British Pharmaceutical Industry in London, in an e-mail to Science Careers. At the University of Liverpool, the Centre for Drug Safety Science collaborates with pharma companies to do research on tissue damage to help with drug safety.

Some new kinds of collaboration are also emerging. Like other big pharma companies, Pfizer is partnering with academic institutions to share the risk of drug development and take advantage of academic scientists' broad base of knowledge, says Boston-based Anthony Coyle, vice president of the Centers for Therapeutic Innovation (CTI) at Pfizer. Pfizer created its CTI program a little more than a year ago, forming partnerships with 19 academic institutions in San Francisco, San Diego, New York, and Boston. At these centers, academic principal investigators and postdocs submit research proposals to Pfizer. Pfizer acts like a granting organization, funding projects it deems worthy in exchange for rights to develop the resulting drug.


Courtesy of Pfizer
Anthony Coyle

These partnerships afford valuable training, mentoring, and networking opportunities, Coyle says. Academic postdocs whose projects are approved spend 50% of their time working in a Pfizer facility alongside Pfizer scientists. The project is too new to have produced any Pfizer hires, but Coyle "absolutely expect[s]" some CTI postdocs to be offered positions.

Snyder hopes such partnerships, combined with the emergence of small companies that serve as drug-development innovators, will allow the pharmaceutical industry to rebound and create new jobs. "I think everyone's job picture is a little uncertain right now … but I'm hopeful that an increased focus on small companies and pharma-academic integration might end up creating more companies and more opportunities. I certainly wouldn't discourage anybody from going into this science, if that's their passion. And maybe it will end up creating some new avenues we can't even anticipate now."

Michael Price is a staff writer for Science Careers.

Elisabeth Pain is contributing editor for Europe.

10.1126/science.caredit.a1100137