Course Philosophy

“Research spirals inward; science cascades outward”. This message, which opened a 2007 article on interdisciplinarity from the National Academies Keck Futures Initiative1, has grown ever more timely, as biological and biomedical science overflow with technology-fueled discoveries, and accumulate virtual mountains of data far faster than analysis can keep up. Methodologies for acquiring and digesting knowledge in biology and medicine now cascade so regularly outward into the domains of physics, mathematics, chemistry, engineering, computer science, statistics, game theory and the social sciences, that interdisciplinarity has become a watchword everywhere that scientists are being trained.

In 2009, the National Research Council (NRC) of the U.S. National Academies of Science and Engineering proclaimed the dawning of an era of “New Biology”, characterized by “re-integration of the many sub-disciplines of biology, and the integration into biology of physicists, chemists, computer scientists, engineers, and mathematicians”2. A subsequent 2014 NRC report on “Convergence: facilitating transdisciplinary integration of life sciences, physical sciences, engineering and beyond”, which stressed the need for “a comprehensive synthetic framework for tackling scientific and societal challenges that exist at the interfaces of multiple fields,” drew heavily on examples from biology and medicine to illustrate promises and challenges associated with interdisciplinarity3. It is perhaps not surprising that, by 2011, the journal Science reported that “30% to 40% of all requests for proposals from the NSF and NIH explicitly required an interdisciplinary approach”4.

Interdisciplinarity has also been highly visible on the international science scene, enough to garner a special issue of Nature highlighting the subject in 2014. That issue included quantitative data5 documenting that interdisciplinarity of publication in the natural sciences and engineering has risen steadily since 1980; that interdisciplinary publications tend to have much greater long-term impact (despite lower short-term impact) than disciplinary ones; and that the life sciences and health sciences are among the areas in which the most interdisciplinary work is being done.

One of the many reasons that have been offered for the global rise of interdisciplinarity in the sciences is the increasing focusing of research on complex, real-world opportunities and problems, which tend not to fall neatly within academic disciplinary lines6. Yet for all the publications that have championed the potential of interdisciplinary research, at least as many have called attention to the unique hurdles that need to be overcome in implementing it. Challenges exist in the categories of funding, education, career development, and evaluation. In this proposal, we focus on challenges in education and professional career development associated with interdisciplinary approaches to biological and biomedical science. In our opinion, the unique history of life sciences professional training in the U.S., which has long tended to emphasize “spiraling in” over “cascading out”, poses barriers to the development of an interdisciplinary workforce, and potentially hinders the career success of trainees attracted to interdisciplinary research. Our motivation in developing this program was to help address the pressing need that this situation has created.

Why Systems Biology?

The term “systems biology” has been applied to a variety of activities that have taken root in biological and biomedical research since about 2000 (although its roots go back much farther). Hallmarks of the systems biology approach include mathematical modeling; the application of engineering and control theory; the analysis and visualization of “big data”; the use of physics methodologies to understand “emergent properties”; the development and application of bioinformatics tools; and the promotion of synthetic biology as a research tool. Concepts in systems biology go beyond the search for cellular and molecular mechanisms, and include the elucidation of dynamics, self-organization, robustness and design.

Not truly a subfield of biology—since it considers every aspect of biology within its purview—systems biology is probably best understood as a “movement”, that is, a concerted effort by researchers and educators to ask and address the questions of life in a way that departs substantially from earlier traditions. At the heart of this movement lies a commitment to tackle the daunting complexity of biology through the embrace of interdisciplinarity. Of course, biology is no stranger to cross-fertilization (one need only think of the physicists who helped launch the molecular biology era), but the kind of disciplinary melting pot that systems biologists advocate (and have to some extent achieved) stands apart from anything in the history of biology (and perhaps even the history of science in general). Although they took pains not to use the name explicitly, systems biology is clearly what the NRC was referring to when it laid out plans for a “New Biology” in 20092.

Why UCI?

Over the past 15 years, world funding agencies have developed numerous calls focused on systems biology, with the most comprehensive plans coming from the U.S. National Institute for General Medical Sciences (NIGMS) who, between 2005 and 2015, designated over 15 “National Centers for Systems Biology” around the country. These centers were charged not only with producing exceptional interdisciplinary research, but also with developing successful approaches to training, outreach and institutional transformation. One of these is the Center for Complex Biological Systems (CCBS), a trans-departmental research unit at the University of California, Irvine. CCBS started in 2001 as a discussion forum among a dozen faculty from biology, mathematics and engineering, and grew into a thriving community of over 100 laboratories, supported by a variety of external grants. Its mission has been to promote systems biology research and training to foster the development of a closely-knit community of biologists, clinicians, physicists, mathematicians, chemists, engineers and computer scientists. CCBS has organized workshops, symposia, retreats, pilot grant competitions, “focused interest groups”, and directly sponsored research. Since 2007 it has administered an innovative graduate (Ph.D. and M.S.) training program, known as Mathematical, Computational and Systems Biology (MCSB), which admits students with backgrounds in mathematics, physics, computer science, engineering, and chemistry as well as biology.

Creating MCSB gave CCBS faculty experience in devising interdisciplinary courses; teaching and mentoring across disciplinary lines; and finding creative solutions for addressing the unique challenges of training an extremely diverse cohort of students. Experimental approaches, such as pre-entry “bootcamps”; one-on-one tutoring; and the introduction of student-centered interdisciplinary seed grants, were tested, evaluated, and implemented. The success of MCSB led CCBS faculty members to develop, in 2009, a “national short course” providing three intensive weeks of systems biology training focused on the topic of “Morphogenesis and Spatial Dynamics”. Applicants came from universities and companies from around the U.S. and internationally. The course was funded by the NIGMS for a total of six years, concluding with a final session in January 2016. The present course builds upon many of the lessons learned during these six years. It also broadens the training mission to include a broader view of systems biology, and to include substantial post-course mentoring.

The Challenges of Interdisciplinary Training

Barriers to acquiring scientific skills usually include not only the greater fund of knowledge and breadth of technical expertise an interdisciplinary scientist needs, but also an expansion and re-alignment of scientific vocabulary (a recent survey on interdisciplinarity on Nature’s website humorously noted how ten extremely common words mean vastly different things in different scientific disciplines [they were: cell, division, equilibrium, color, cis, translation, concentration, matrix, fishing expedition and substrate]). Ontology mismatch7 refers to the fact that different disciplines often have very different standards for what counts as suitable explanation. To a molecular biologist, a mechanistic description of how the gene products in a network talk to each may be a satisfactory explanation of the network, but a physiologist might be dissatisfied with anything less than a statement about what the network was “for” in a functional sense; an engineer might demand an accounting of the basic design principles that enable the network to perform its function; and an evolutionary biologist might require an accounting of how the network may have evolved, or is at least maintained under selection. In contrast, epistemology mismatch refers to field-specific differences in what counts as suitable observations to support a scientific conclusion. In some disciplines, it may suffice merely to have qualitative observations that fit a preferred model; in others, quantitative observations are the gold standard (with required degrees of precision varying greatly among fields). In others one may be obliged to consider the locus of all possible models, whereas in still others, arguments based on plausibility or simplicity (e.g. Occam’s razor) hold great sway.

Some of the significant challenges faced by trainees seeking interdisciplinary careers in biology and biomedical science.

At the same time, several career advancement skills (sometimes called “soft skills”), which can benefit all members of the scientific workforce, can be especially important and challenging for the interdisciplinary trainee. Effective communication, whether oral or written, across disciplinary lines requires a great deal more training and practice than communication within a narrow discipline, and mastering the necessary skills can have an enormous impact on the ability of the interdisciplinary trainee to defend a thesis, find a job, advocate for projects, and achieve lasting success. We also find that good listening skills are essential to enable trainees to take in foreign ideas and not dismiss them reflexively. The fact that many interdisciplinary projects, whether inside or outside of academia, often require the work of teams6,8 means that leadership skills and good collaboration skills are especially necessary for the interdisciplinary scientist. And because only a subset of scientific problems may be ripe for interdisciplinary attack at any one time, the interdisciplinary scientist needs to develop a keen sense of risk assessment, so that he or she may both avoid problems that are not yet ripe, without being too easily scared away from those that are.

Still other challenges facing interdisciplinary careers fall into the institutional category, e.g. how departments, universities, journals, and industries foster, assess and reward interdisciplinarity. Although addressing institutional change is not within the scope of this short course, helping trainees develop the skills they need to navigate the hurdles they will face in this area is.

References

1. Porter, A. L., Cohen, A. S., Roessner, J. D. & Perreault, M. Measuring researcher interdisciplinarity. Scientometrics 72, 117-147, (2007).

2. Connelly, T. et al. A New Biology for the 21st Century: Ensuring the United States Leads the Coming Biology Revolution. (The National Academies Press, 2009).

3. National Research Council (U.S.). Committee on Key Challenge Areas for Convergence and Health. Convergence : facilitating transdisciplinary integration of life sciences, physical sciences, engineering, and beyond.

4. Pfirman, S. & Begg, M. in Advice, Issues and Perspectives Professor and Vice Dean for Education at the Mailman School of Public Health and Co-Director of the Irving Institute for Clinical and Translational Research at Columbia University in New York (Science (AAAS), 2012).

5 . Van Noorden, R. Interdisciplinary Research by the Numbers. Nature 525, 306-307, (2015).

6. Ledford, H. Team Science. Nature 525, 308-311, (2015).