Physician-Scientist Careers in the Biotechnology and Pharmaceutical Industries

Abstract

Many careers are open to physician-scientists in the biotechnology and pharmaceutical sectors. However, research is structured very differently in these environments compared to academic medicine. This article highlights these differences and the reasons for them, then outlines the different career paths available to physician-scientists in the variegated worlds of biotechnology and pharmaceutical companies.

The contributions and roles of physician-scientists in research in academic clinical departments are well recognized. Discussions of the physician-scientist career path in the medical literature have typically focused on their criticality to the missions of academic medical centers and on ways to sustain their numbers in national training cohorts [1–3]. This academia-centric focus is not limited to US perspectives, but also dominates international analyses of the subject [4, 5]. Surprisingly, the roles of these individuals in the biotechnology and pharmaceutical industries have been much less widely examined. Here I discuss how physician-scientists are integrated into the complex ecosystem of the biopharma industry, and consider how this relationship is likely to evolve in the future.

SCIENCE IN THE ACADEMY AND INDUSTRY: DIFFERING GOALS AND STRUCTURES

Before examining these issues, it is well to step back and consider the differing missions of academic and industrial research in biomedicine. The primary mission of academic biomedical research is the generation of new knowledge; by contrast, the mission of industrial research is the generation of a product, for example, a drug or vaccine. Certainly the quest for the latter is a knowledge-intensive one that is critically dependent upon recent discoveries in academic science, but the mission is nonetheless a very different and distinctive one. Academic research begins with a question—sometimes a very focused one, but often a very broad or profound one. Industrial research begins (usually, at least) with something very different: a target product profile (TPP). The TPP defines the properties of the medicine or product that the research effort is designed to make. It includes the disease state the drug is intended to treat, the selection of the molecular target of the drug (this is the part that is most heavily dependent upon academic research), whether the envisioned drug is a small molecule or a biologic, and the route (and frequency) by which it will be administered. Clearly, formulation of an achievable TPP requires a great deal of knowledge (much of which is clinical and therefore especially within the wheelhouse of the physician-scientist; see below), but the important point here is that the primary goal of the effort is to use existing knowledge to define the TPP and then design a research plan (usually screens and counterscreens) that will allow the TPP to be embodied in the product. Although new knowledge is sometimes generated during such a program, it is never the sole objective, and the quest for such knowledge is often a distraction that can delay or can even derail the program. Certainly, there are times when a project team will conclude, as a result of experiments conducted in pursuit of a given TPP, that the objective is not possible at the present state of knowledge—but this usually triggers abandonment of the objective rather than launching of a quest for the missing knowledge, a pursuit that may take years and is generally not compatible with the timelines under which industrial research operates.

To achieve these very different objectives, universities and companies structure their research efforts very differently. Academic biomedical research largely operates on a cottage industry model whose basic unit (cottage) is the individual research group, led by a principal investigator (PI) and composed of graduate students and postdoctoral fellows. This group is largely autonomous and self-sufficient; certainly such groups can engage in collaborations with other groups, especially when they need to employ techniques with which the group lacks expertise. However, such collaborations are usually transient, as the criteria upon which success is judged in academic science focus on the degree of independence and the perception of originality shown by the group’s PI. This model encourages and rewards imagination, ingenuity, and originality—all key aspects of knowledge generation. But it is not designed to convert those new ideas into products. The emphasis on attribution of credit to one individual or group virtually guarantees that most such collaborations will not last long, and is the major cultural force opposing teamwork and shared effort in academic science.

Industrial laboratories are structured very differently: Groups of scientists are assembled from diverse domains to create a project team with all the capabilities needed to achieve the TPP. Such teams can be large, including biologists, biochemists, crystallographers, medicinal chemists, pharmacologists, and (later on) toxicologists. Team composition is fluid, with subteams delegated to solve certain issues while other parts of the team advance their parts of the project. Leadership of a team may change several times during the life of a product; biologists are typically in charge when bioassay development and screening are the main activities, but projects often transition to leaders who are expert in medicinal chemistry when lead optimization is the order of the day. (Once the TPP is preliminarily achieved and proof of efficacy and safety in animals is obtained, projects transition to being directed by clinical investigators, who design and conduct the key clinical trials required for proof of human efficacy and registration with the US Food and Drug Administration [FDA].) Unlike academic science, in which emphasis is on individual achievement, in corporate work the reward is for smooth and efficient teamwork and the early attainment of project goals.

Scientists contemplating a career in industry need to consider the above differences carefully as they make their decision. It is a fantasy of some postdoctoral fellows that a career in industry consists of asking open-ended scientific questions of the type they are accustomed to, without the pesky constraints of having to apply for grants. Nothing could be further from the truth. The decision to opt for a career in industry should be based on an underlying commitment to applying cutting-edge science to the development of effective therapeutics (or diagnostics or preventatives) for human disease. If this is not an interest of yours, don’t even think about applying to an industrial job. Certainly this quest will involve solving many sophisticated scientific challenges along the way, but the resolution of those conundra is, in industry, the means to an end, not an end in itself.

The expression industry scientists use to encapsulate this philosophy is “staying on the critical path.” That is, team scientists can address any and all problems directly related to advancing the project, but must avoid the siren song of interesting issues that may arise that are tangential to said mission. Obviously, judgments about what is and isn’t critical are not always easy, and companies do vary in the latitude they give team leaders to adjudicate such issues. (Small, financially stressed startups are typically much more stringent in their demands that teams stay on a narrowly construed path.) But in no case will a team leader allow such a quest to derail or redirect the entire project away from its therapeutic mission.

PHYSICIAN-SCIENTIST CAREERS IN INDUSTRY

In most firms, the bulk of physician-scientists are employed as clinical investigators. While laboratory science training is not essential to being hired into a clinical investigator unit, it remains highly prized in corporate clinical development teams. The reasons are several. First, these individuals often advise preclinical science teams. At the early stages of a project, they supply the clinical expertise needed to help shape the TPP; in many firms, they also consult with the basic science teams as the program matures through hit finding and (especially) lead optimization and selection of candidate compounds for the clinical trials. As such, being at home with the vocabulary and culture of preclinical science is a considerable plus: It allows the physician-scientist to help shape the program at multiple points in its evolution, and avoids potential errors that may arise from miscommunication between laboratory scientists and clinicians. It also helps the clinical team think about what kinds of monitoring the trial will need to implement—often a key step in assuring that the new drug is being dosed correctly in the clinic.

It is important to recognize that if a physician-scientist wants to pursue a career in clinical development, he or she will need to complete not only a primary residency but also training in a subspecialty. Since clinical knowledge is at a premium in this role, it is important for the would-be clinical investigator to have deep roots in a subspecialty; there are few positions available in development organizations for those lacking subspecialty board eligibility. Interestingly, while prior direct experience with clinical investigation is usually a plus, in many companies this expertise can be acquired on the job by those hired into entry-level positions. Obviously, being hired into more senior roles in clinical development organizations does require direct experience with clinical trial organization. Typically, such jobs are awarded preferentially to those who have substantial experience running trials in the industry setting, as leadership positions in this sector of the industry often involve substantial interaction with commercial partners, government regulators, and payers—interactions that are seldom part of an academic career.

Following 7–10 years as clinical investigators, numerous other options usually open up for physician-scientists in clinical development. Because they have acquired extensive experience with the governmental regulatory hierarchy, they often can take leadership positions in divisions of regulatory affairs, the departments in large pharma companies that advise the teams on regulatory strategies. Another well-traveled path for physician-scientists in development organizations is to migrate to senior roles in business development, the branch of companies that deals with in-licensing of novel therapeutics from other firms, as well as mergers and acquisitions of companies. Going down this path usually means forsaking active participation in clinical trials, and learning the vocabulary of finance officers, venture capitalists, and other businesspeople. However, knowledge of science and medicine remains critical here, as every acquisition discussion begins with these questions: (1) How good is the science behind the asset being acquired? (2) Does it address an unmet medical need? (3) How does it stack up against competitor compounds? These are precisely the questions the physician-scientist is in a perfect position to adjudicate.

Surprisingly, in most firms (especially in smaller biotechnology firms), physician-scientists are underweighted in the ranks of preclinical scientists, which are heavily dominated by PhDs in the relevant disciplines (eg, biochemistry, cell and molecular biology, structural biology, immunology, neuroscience, pharmacology, synthetic and medicinal chemistry). Mostly, this is a reflection of the greater numbers of PhDs in these fields but is also partly a reflection of the lesser costs associated with hiring them, relative to MD-PhDs. However, the value of admixing physician-scientists into this early setting has been recognized by several firms, and a few have made it a point to hire biologically and clinically literate physician-scientists into leadership roles in the preclinical research arm of the business. In general, the physician-scientists who have become leaders in preclinical research in pharma companies have tended to enter industry after long and successful careers in academic biomedicine, during which time they not only established deep scientific literacy but also maintained their clinical credentials and interests. The latter are important to companies because, after all, the medicines they make have to fit into the realities of current medical practice. Therefore, a deep awareness of the landscape of current therapy options and their costs/toxicities/ limitations is mandatory, as is a more general fluency with other aspects of contemporary medical practice—for example, the pressures on length of hospital stay, the trends in home intravenous therapy, the roles of antibiotic stewardship, and other regulatory phenomena. Those who abandoned practice soon after their residency do not bring this kind of skill set to the table and are unlikely to be competitive for such top positions.

OTHER CULTURAL ASPECTS OF LIFE IN INDUSTRY

The above remarks have focused on the goals of industrial science, how they differ from those of university research, and how those differences engender a different research structure and culture in industry. But there is another difference that also shapes the culture inside a firm. In academia, there is no mission other than the generation of knowledge. In pharmaceutical companies, however, the research mission exists side by side with 2 other missions: manufacturing of the drug, and commercialization of the resulting product. These 2 activities are far removed from research and their cultures are not even remotely influenced by academia or by the firm’s own research organization. The manufacturing side is influenced more by traditions that derive from other high-tech manufacturing sectors, including chemical manufacturers, aerospace and computer hardware firms, etc. These traditions involve optimization of synthetic routes, quality assurance, supply chain management, and the cost of goods; these are important issues but have little impact on the environment of the research and development (R&D) operation. The commercial side is even more divergent from the research enterprise, but paradoxically can have a greater impact on its culture. Although its job is to sell the firm’s drugs to physicians and hospitals, which requires some physician input, most commercial leaders have no medical lineage; the culture of commercial units tends to be dominated by ideas emanating from the worlds of finance, sales, and marketing—worlds with which the average physician-scientist is largely unfamiliar (and toward which many are either indifferent or hostile). Wall Street and its imperatives loom particularly large in this critical portion of the industry. Current Anglo-American capitalism is in thrall to the notion that creation of shareholder value is the primary mission of public companies—and shareholder value is inspected on a quarterly basis. This creates a strong push on the commercial side toward rewarding short-term thinking. Since it is the commercial side that generates the profits from which the research budget is derived, in many firms those same short-term pressures can reach down into the research organization and subtly but unmistakably influence research directions and practices. Leaders of the most successful firms have found ways to blunt or mitigate these influences, but the pressure is unremitting and, like the steady drip of water on stone, threatens to erode the will of all but the most resolute of R&D directors. At one extreme, there are firms in which commercial forces almost entirely drive R&D prioritization; such firms tend to have disempowered research operations that grow accustomed to taking dictation from their commercial; over time, such firms have trouble attracting or retaining top-notch scientists. Firms that have been able to separate R&D from commercial units have generally fared better in terms of maintaining the caliber of their research staffs, but often at the cost of inefficient transfer of assets from one part of the operation to the other. How to reconcile these competing forces is one of the least recognized—but most important—unsolved problems in pharmaceutical management.

I dwell on these matters because many of the ancillary aspects of life in industry result from traditions and practices that emanate from the business world, not from science. For example, university researchers are accustomed to tenure, or at least to multiyear commitments or contacts, but these are unknown in industry, where even the most senior researchers (and executives) are subject to annual renewal based on performance. Although between World War II and the 1970s, employment in the pharmaceutical industry tended to be very stable, with solid researchers being able to spend most of their careers at a single company, those days no longer exist; trainees now taking jobs in this sector should expect to work at multiple firms over the course of their careers. In addition to the normal churn caused by individual turnover, firms not infrequently restructure their research priorities, exiting whole areas and entering new ones. When that happens, layoffs of several entire research teams can be the result. The good news is that other firms looking to hire staff generally do not regard such layoffs negatively—they understand that these result from corporate decisions rather than individual shortcomings. In fact, because industry experience is highly prized, those released in such layoffs can often rapidly find new employment if they were in good standing at their prior firm and if the overall healthcare sector is not in recession. When comparing job security in industry with that in academics, it is also well to remember that despite the formal assurances of tenure in university life, loss of grant support usually results in major difficulties maintaining a viable presence on a university faculty, and that opportunities to rescue an academic research career following loss of a university position are few.

I am often asked about work-life balance in industry. It is hard to generalize, since small and large companies face different pressures. Startups in biotech often have limited staffing, with the result that the existing staff must stretch its efforts to get all the requisite tasks done. When crises erupt, such as the need to meet a deadline for a regulatory or patent filing, it is sometimes a matter of “all hands on deck,” whether it is within traditional working hours or not. Larger firms, for the most part, are staffed to avoid these difficulties and there, more predictable work hours tend to be the norm. Considering how many demands are made on one’s time in academic medicine, in terms of teaching, clinical care, administration, and research (not to mention pro bono work like manuscript reviewing), on the whole I think it defensible to say that work-life balance is probably more regularly achieved in industry—although exceptions to this dictum surely exist.

OPPORTUNITIES FOR PHYSICIAN-SCIENTISTS TO INTERACT WITH INDUSTRY WHILE IN ACADEMIA

In the past, it has been difficult for academic physician-scientists to interact with their counterparts in industry, save for participating in an industry-sponsored clinical trial at their medical center. However, this landscape is slowly changing, although not always for laudable reasons. In the first decade of this millennium, the view became ascendant on Wall Street and in US business schools that in-house research at Big Pharma companies has little value. This was based on the fact that the sizable escalation of R&D budgets by Big Pharma in the 1990s did not yield a proportional increase in registration of novel drugs with the FDA. Of course, this interpretation is scientifically illiterate; it takes 20–30 years for an initial investment in research to lead to development of a novel drug based on that research [6]. Moreover, since every success in drug development raises the bar for registration of the next drug in that field, drug development becomes progressively more difficult with time—a paradox that puts the lie to simple-minded thinking about drug pipelines based on other research-intensive fields like computer science or electrical engineering.

Nonetheless, under pressure from Wall Street, many Big Pharma companies have slashed their internal research budgets and drastically reduced their internal research staff. In the belief that true innovation comes only from academia or small biotechnology companies, some of this money has been diverted to those venues. This has contributed to a recent boom in the biotech sector, but has also led some firms to invest in academic–industry partnerships. These take many forms, but usually involve grants to individual PIs or groups of PIs. These awards are welcome in academia in times of tight federal grant support, but they rarely result in true partnerships between university scientists and their industry counterparts, in no small measure because of the huge differences in research goals, structures, and culture mentioned at the beginning of this article. On top of those issues, firms can rarely afford to allow mission-critical work in their fields to go on in settings outside of their control, since they would lose intellectual property rights that will be essential to commercialization. As a result, the academic work they fund tends to be rather basic and not immediately related to drug development. This is fine, but academic scientists should not expect that by entering into such agreements they are going to be able to experience what industrial science feels like without having to leave the university. However, such industry-academic contact may provide a venue for academic scientists to get to know some of their peers behind the industrial veil, as firms often make certain technical capabilities (eg, high-throughput screening, metabolomics, or pharmacokinetics) available to their academic partners on a limited basis, as appropriate to their projects.

CONCLUSIONS

Training as a physician-scientist opens the door to a plethora of different opportunities in industry, many of which offer unique opportunities for professional advancement and career satisfaction. But it is imperative that those electing this option understand that they are entering a world with very different predicates and goals from the one in which they trained. Careful consideration of those differences in advance can usually lead physician-scientists to an informed decision that will fit well with their own talents and aspirations.

Notes

Supplement sponsorship. This work is part of a supplement sponsored by the Ragon Institute of MGH, MIT, and the Harvard University Center for AIDS Research P30 AI060354.

Potential conflicts of interest. D. G. is an employee and shareholder of Novartis. The author has submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

References