In biopharma, we are faced with the problem of understanding human disease well enough to intervene for patient benefit. Due to the complexity of human biology and limitations of traditional laboratory reductionist approaches to discover new basic biologic concepts, innovative perspectives from biology, technology, drug discovery, computational, translational and clinical scientists are needed to discover and develop transformative impactful therapies to help patients. This mindset requires constant questioning of existing paradigms and challenging the status quo to evolve. At Genentech, innovation is ingrained in our culture and is required not only for near-term success but also needed for us to flourish in the long-term as an innovation engine in a highly competitive external environment. Senior leaders must “walk the talk” and exemplify the innovation mindset. We must consistently and purposefully emphasize this mindset and devote resources (time, energy, fostering interfaces and funds) to support a broad spectrum of activities to incentivize and enable creativity.
Interfaces and Colleagues as a Foundation for Innovation
Innovative drugs never emerge based solely on the work from a single individual. Successfully traversing through the “valley of death” of drug development to translate new basic scientific concepts to patients often requires a new approach or insight that arises at the interfaces between disciplines. For example, if a biologist discovers a new biological pathway, successful drug discovery and development requires collaboration across multiple disciplines to identify the appropriate disease or patient subset exhibiting dysregulation of the new pathway, discovery of a new drug and clinical testing potentially with novel endpoints. Similarly, for technology focused scientists, interaction with biologists is critical for understanding how to use or develop a new class of molecules or a new device for patient benefit. Biologists often stop or even fail to start discovery projects if they believe a target is “undruggable”. Bi-directional exchange of ideas between technologists and biologists may provide an opportunity to test new drug discovery approaches not known to the biologist; conversely, the need to perturb an “undruggable” target may stimulate a drug discovery scientist to pursue an entirely new approach to address the biological need. These and other interfaces across disciplines provide the nidus to highlight new needs and opportunities for innovation. Further, as each field becomes more complex and specialized, it becomes ever more necessary to communicate cross disciplines. At Genentech, we emphasize the importance of these interfaces and foster dialogue, collaboration and forums within and across disciplines to increase these opportunities for innovation.
In my 19 years and counting at Genentech, I learn daily from my colleagues. We are fortunate to have both breadth and depth of scientific, clinical, regulatory, legal and business experts and a culture that breaks barriers. I also have learned that the culture of innovation is not restricted to scientists: the successful development of new drugs requires creativity from our clinical, regulatory and business colleagues as well. While I cannot and will never be expert in each of these fields, working closely with these colleagues makes it possible for me (and presumably, them) to constantly obtain a deeper level of understanding beyond my current expertise. With time, each of us accumulates a deeper and broader knowledge base to enable greater abilities and expertise to innovate. Often, this constant learning is mentally exhausting, but at the same time mentally exhilarating to then think about the “What if’s?”
Mastery, Breadth and Continuous Learning
Focusing on science, most biological pathways are conserved across species, though the details, especially about the rheostat controls often differ. While there are still truly new biological paradigms to be discovered, most “new” discoveries in retrospect have been previously described in different systems or species. Similarly, new technologies that inform biology efforts often draw on advances made in related fields. Hence, the ability to make a “new” and important discovery can often be enabled and accelerated with a broader scientific knowledge base. While we all need to focus to maintain mastery in one’s own discipline, one also has to make concerted efforts to read and broaden beyond one’s own research area- i.e., to also become a generalist. This breadth may provide additional insights to accelerate one’s future research. Conversely, one’s mastery may be applied to a totally new system to break open an evolving field. Understanding of the clinical, regulatory, and business barriers to getting medicines to patients also can influence the way a scientist approaches a particular problem, even at the earliest stage of investigation.
I find the need to constantly expand my knowledge base, to anticipate and to successfully solve problems to be the greatest challenge in my own day-to-day work. Organizational responsibilities, family priorities and day-to-day life makes conflicting demands on every researcher’s time. To grow and not be left behind in the fast-evolving world of science, I reserve a significant block of time during the work week (i.e., not just the late evenings or the weekend) to read outside of my areas of interest, to flip journals (yes, I still get the hardcopy) and to explore specific topics that intrigue me that particular week. We are also fortunate at Genentech to have many internal and external speakers on topics very much outside my areas of comfort or familiarity. While I may not understand the technical details of a particular seminar, understanding the capabilities and potential of a field provides me a higher level of understanding of what is possible. Finally, as a leader at Genentech, I try to reiterate to our scientists the need for them to ensure that they invest in themselves and prioritize protected time to “read and think” as a necessity and not a luxury.
Failure as a Form of Learning
We do not like failure, but an innovation mindset requires failure to be part of an acceptable outcome. The Genentech culture strongly supports high risk, high reward solutions to important problems; implicit in “high risk” is that many of these approaches will fail. Importantly, as we pursue new ideas or hypotheses, it is important for us to identify “killer experiments” to disprove our ideas. And if the “killer experiment” tells us that our high-impact hypothesis is wrong, it is incumbent for scientist, team and organization to move on to a new high-impact hypothesis. But the culture of “failing early through rigorous experimentation” has to be celebrated and not feared. At Genentech, we celebrate both our project successes as well as project failures. The latter is often extremely informative for next generation hypothesis or projects. I make a point of highlighting in my organization-wide talks how teams identified critical experiments to make these important science-driven “no-go” decisions. Interestingly, some of the most innovative discoveries are based on open minds analyzing unexpected results from the “positive” or “negative” controls, rather than the actual experiment.
Colleagues Support Innovation
The culture of “killer experiments” is greatly aided by having a group of collegial and collaborative colleagues who are willing to critique one’s ideas and data, offer constructive orthogonal experimental approaches and often contribute their own expertise to experiments. A collaborative environment of “truth-seeking”, rather than “project advancement” is critical to truly create an innovation culture. I myself have benefitted from many of my Genentech colleagues’ ideas in advancing my own research and have had the privilege of witnessing how this collaborative and nurturing environment motivates our researchers leading to synergies to do what was improbable. Unfortunately, I have also on occasion witnessed how non-supportive and non-collaborative environments alienate and disincentivize researchers from making progress.
Organizational Incentives for Innovation
As leaders, it is incumbent on us to foster and enable an innovation mindset. We are continually exploring how we can empower our scientists to create and implement testing of innovative ideas. In addition to supporting innovation within our everyday work, we at Genentech have created new outlets to promote new idea generation and execution of these ideas as a necessary part of our scientific lives. These include having a robust post-doctoral training program which enables us to bring fresh perspectives onto campus and gives the post-doctoral fellow mentors resources to pursue fundamental questions that are often outside of the context of our drug discovery efforts. Similarly, we created an “innovation fund” where individual researchers can apply for resources to pursue discretionary ideas outside of normal management channels. These proposals often explore new technologies requiring capital investment. Further, we encourage cross-functional new idea forums to break down departmental silos and foster free-form brainstorming.
One of our recent experiments at Genentech is the creation of an “Innovation Incubator”. We asked a group of our Staff Scientists (the title for our most experienced and accomplished scientists) to create a mechanism by which researchers can pursue new high-impact ideas that are not presently within Genentech’s portfolio. Researchers submit a < 3 page proposal to the Incubator Committee (consisting of the Staff Scientists) and discuss their ideas and goals in person with the committee detailing experimental approaches and milestones. Often, the proposal evolves with the input of the highly accomplished Staff Scientists. Selected researchers are relieved of most, if not all, of the company responsibilities, devote from half to 100% of their time and are provided the necessary support resources to pursue their proposal. Their progress is mentored and monitored by the Staff Scientists. “Management” does not interfere with evaluation or decisions of the Incubator Committee. To date, successful proposals have ranged from using artificial intelligence to calculate molecular energies, to novel drug delivery technologies, to exploration of multi-mechanistic cellular therapies as well as to advancing new technologies for cryo-electron microscopy.
There are many additional mechanisms that we and other organizations use to foster innovation. There are no single simple solutions, and continued success at innovation requires a multi-modal approach to support different perspectives and working styles. Regardless, putting Innovation and Continuous Learning at our forefront is requisite for us to flourish.
And now, back to reading and exploring. Acknowledgements- I thank my colleagues Eric Brown, Sarah Hymowitz, Andrey Shaw and Melissa Starovasnik for helpful suggestions and critical reading of this work.
Dr. Andrew Chan joined Genentech, Inc in 2001 as Senior Director of the Departments of Immunology and Antibody Technologies, named VP and SVP of Research-Immunology in 2003 and 2007, respectively, and appointed SVP-Research Biology in 2010 where he oversees biological research at Genentech. He is also Associate Professor of Medicine at UCSF.
Chan received his BA and MS degrees in Chemistry at Northwestern University, MD and PhD degrees from Washington University (WUSM) and completed his internal medicine residency at Barnes Hospital and rheumatology fellowship at UCSF. He joined the faculty at WUSM in the Departments of Medicine and Pathology and was a member of the Howard Hughes Medical Institute. His research focuses on signaling mechanisms of immune cells, immunobiology of immunodeficiencies and autoimmunity, human disease heterogeneity and mechanisms of immunomodulatory therapies. Chan is a co-inventor of ocrelizumab approved for the treatment of multiple sclerosis.
Chan serves on the National Council of WUSM, National Research Advisory Council for WU, Russell/Engleman Arthritis Center Board, Medical Scientific Advisory Committee of the Arthritis Foundation and Chemistry Life Processes Institute at Northwestern University. He is a member of the American Association of Physicians, American Society for Clinical Investigation, Henry Kunkel Society and a Pew Scholar.