In the spring of 2006, Laura Gault was frustrated. A clinical faculty member in the autism clinic at Yale University, Gault was doing something she loved -- working with children -- but her inability to offer these desperate young patients and their families better interventions was beginning to gnaw at her.
A self-described "real geek" as a child, Gault had pursued a medical degree and a Ph.D. in neuroscience at Case Western Reserve University  in Cleveland, Ohio, as well as a child psychiatry residency at Yale School of Medicine . "My interest my entire life has been in asking and answering a question. That's what drove me," Gault says. But at Yale, she found she wasn't drawing on her research skills when she immersed herself in clinical duties. "I'd never intended to spend all of my time in the clinic," she says. "The clinical frustration combined with my inability to do research served as a wake up call telling me that I wasn't where I should be."
It's true, Gault says, that she probably could have arranged for protected time to conduct research, but it wouldn't have happened quickly, and she would have found it difficult to stay away from the patients who needed her. So she began to explore alternatives where research would be her primary responsibility. She landed at a pharmaceutical company: Abbott Laboratories  in Abbott Park, Illinois, leading their pediatric attention deficit hyperactivity disorder (ADHD) program. "Being anchored in my clinical specialty [child psychiatry] made it pretty easy to make the jump into industry," Gault says.
Gault is in good company. After thoroughly analyzing their personalities and interests, many M.D.s, M.D./Ph.D.s, and Ph.D.s find their best match in industry. That's not surprising when you consider the crucial role for-profit industry has always played in the development and deployment of basic scientific discoveries.
Choosing a career in industry may seem risky at a time when the pharmaceutical industry has shed many scientific jobs as a result of the global recession and looming restructuring of the drug-development process. However, many industry insiders say these changes are opening up unique opportunities for researchers who focus on translating basic science into real-world cures and are eager to explore the molecular mechanisms of disease, test hypotheses, and do work that benefits patients.
The opportunity to directly help patients is a powerful attraction to the pharmaceutical industry for some scientists, especially scientists with medical training. Bruce Littman, president of Translational Medicine Associates, LLC,  in Stonington, Connecticut, moved to an industry position at Pfizer  after studying the pathogenesis of rheumatoid arthritis as a professor at Virginia Commonwealth University  in Richmond. The decision to move to industry was born of a desire to work someplace "where the focus was still very much on the science but there was still a likelihood that my work will have an impact on human health within my lifetime," he says.
Mario Saltarelli, who once worked with Littman at Pfizer, concurs, noting that after he had completed medical school, a neuroscience residency, and a Ph.D. in neuropharmacology, he found that studying epilepsy as an academic clinician didn't adequately exploit his skill set. He was participating in some industry clinical trials, but the route to helping patients wasn't direct enough. The move to industry has allowed him to "bring therapies to millions of people who weren't able to be helped," says Saltarelli, now divisional vice president for neuroscience development at Abbott Laboratories.
Although the work may benefit patients more quickly, economic considerations can bring projects -- and, hence, a life's main professional pursuit -- to an unceremonious end. Gault got a lesson in this roughly 9 months into her work at Abbott when the ADHD program she was working on was discontinued.
Gault transferred to a new research area -- Alzheimer's disease -- where she is now responsible for several proof-of-concept trials, also known as phase II clinical trials. "I think this really drove home to me something I already knew: In industry, it is highly unlikely that you will study the same thing for your entire career," Gault says. "Things in industry change more quickly, and you have to be adaptable."
Despite the opportunities industry affords, it's not for everyone. Scientists exploring industry careers "have to have the right motivation, the right type of inquisitiveness, and have to enjoy working in a team. It's a different culture," Saltarelli says. "Part of the thing you give up when you come to industry is that you are not your own individual; you are part of a larger team, and it is because you are part of that team that you are able to do all the things you do in industry."
Gault agrees that the culture of corporate science takes some getting used to. "You live and die by Lotus Notes," she says, laughing. "Everything is highly scheduled. The work is more goal-oriented and results-oriented because it has to be."
Every step in the process, from preclinical studies to proof-of-concept clinical trials, has to take place on a timeline to prepare the product for pivotal testing, Gault says. Delays can have cascading and devastating effects on the development of a therapeutic. "You have to think about timelines in a way that you don't in other environments," Gault says. "I like it, but not everyone will."
Although pharma-industry positions have long been considered stable, the global recession and fundamental concerns about the way drugs are developed have resulted in massive industry layoffs over the past 2 years.
Those layoffs were driven in part by the skyrocketing cost of developing drugs. Many believe the drug-development enterprise is unsustainable in its current form, where a company maintains all aspects of research and development in-house. "What we are likely seeing is that the model of a vertically integrated pharmaceutical company capable of taking a molecule from discovery to market is in the process of disintegrating," says Garret FitzGerald, chair of the Department of Pharmacology  and director of the Institute for Translational Medicine and Therapeutics  at the University of Pennsylvania.
The traditional notion of an "industry career" is changing right along with changes in the industry. In an effort to more efficiently develop drugs, the pharmaceutical industry is focusing on highly targeted, smaller clinical studies. As a result, the emphasis in early development is on understanding the molecular underpinnings of disease and developing markers for therapeutic effects.
"I see it as an opportunity," says James Chung, medical sciences director for early development at Amgen Inc.  in Thousand Oaks, California. "The blockbuster model has had its day. It worked because there were very large markets where getting 20 to 50% of the market share with a single drug was profitable. It was low-hanging fruit. The challenge and question now is, how do you develop a sustainable business model for developing drugs for smaller patient populations?"
Scientists whose expertise is in the molecular basis of disease can now apply "the tools of small molecules to cast about hypotheses. It is an extraordinary opportunity," Littman says, noting that most people who choose this path have a clinical background of some sort as well as a strong interest in understanding disease whether they have an M.D. or a Ph.D.
The focus on early development also means opportunities for research on biomarkers to help define the patient populations most likely to benefit from a particular therapeutic intervention. Saltarelli notes that the concept of using biomarkers to conduct smaller trials to test drugs wasn't widely embraced by industry 10 years ago. "There has been a change over the last decade, and companies are putting value on early clinical trials," he says.
Working at an early stage of drug development means dropping drugs that look like they aren't going to be safe and effective, as early in the process as possible. "I see my job as figuring out what kind of legs a drug has, and sometimes the answer is that it isn't going to be efficacious or safe enough," Gault says. Littman adds, "A company that follows the evidence will be happy if you kill their drug quickly and cheaply."
This kind of research generates an enormous amount of data. Mining that data is critical to developing therapies that target key points in relevant biological pathways -- and represents opportunities for bioinformatics experts, Chung says. "There is a huge amount of data coming through, and there is a bottleneck in making sense of that data. In my mind this is the frontier, and it requires people who have both the computational and the biological background."
Despite all the changes, pharmaceutical companies are maintaining a strong internal development program in areas with large markets such as oncology, neuroscience, and diabetes/obesity; and they are hiring people whose skills fit with their drug-development programs. Furthermore, the shifts in the industry may herald a new, more fluid division of labor where nontraditional partnerships take on the earliest stages of drug development. "I think it may be up to smaller biotech companies and academia to come up with new drugs," Littman says. "And smaller biotech companies are very interested in generating biomarkers, working on proof of concept, and testing in smaller patient populations."
It's a modular approach to drug discovery and translational research that both FitzGerald and others believe will become prevalent. They also think this will necessitate changes in the way industry and academia handle things such as intellectual property. People choosing industry careers should be prepared and adaptable.
"I think there is a lot of uncertainty out there in the world right now," says Will West, chief executive at CellCentric , a biotechnology company in Cambridge, United Kingdom. "If you are a young graduate, I can see how basing a career in industry may seem like a difficult choice to make. I see the opposite. I think in a changing model, there is opportunity for bright people to take advantage of that change and be drivers for the solutions."
Photo (top): D. Sharon Pruitt 
Lisa Seachrist Chiu is a science writer in Washington, D.C., and author of When a Gene Makes You Smell Like a Fish ... and Other Amazing Tales about the Genes in Your Body.