Abstract
I recently said to Lila, my wife of 25 years, that I had just realized that “science defined my life”. She responded by telling me that she knew that 25 years ago… The story, though, is that it might not have been, and the journey to get to where I am today was a highly circuitous one, taking me places I never thought I would see. Nevertheless, today I can look back on a career as a scientist that has been both fascinating and fulfilling, and…, perhaps the only life I could have lived in complete happiness. My only hope is that, before my career is over, I can give back as much or more than I have received from science.
In September, 1959, when I was seven, we moved from a small town in southern Michigan to a house on a hill overlooking Sand Lake, surrounded by woods. When we moved in, we had no running water, no heat, no insulation, and no electricity. To me, a small child with an active imagination, it was heaven. To my poor mother, it was something else entirely. We finally did get heat, water and electricity, and eventually, we made a real home out of it. I spent hours a day in the woods, following animal trails, finding fox dens, and bringing home knapsacks of snakes and snapping turtles to my very understanding mother, who calmly threw them back into the woods when I wasn’t looking. I was fascinated by the nature that surrounded me. In 1961, my mother’s brother, Russell Steere, came to visit us at the lake. He brought with him his 3 × 5” lantern slides, his bulky lantern slide projector, and his passion for science. Uncle Russ was a naturalist, virologist, and PhD-trained physicist, and was the head of the Plant Protection Institute at the USDA in Beltsville. He also was the inventor of the technology known as freeze-etching. I was fascinated by the grainy freeze-etch pictures of tobacco mosaic virus and the stories about research that Uncle Russ told me. A life as a world-class scientist became my secret passion, but I grew up thinking it was well out of my reach. It turned out that Russell Steere was not the only scientist, or scientific influence, in my family. During visits to my great aunts’ house in Ann Arbor when I was growing up, the Aunts regaled us with stories of their father, Joseph Beal Steere, who was the founder of the University of Michigan Natural History Museum. Joseph Steere was a great naturalist and ornithologist of the late 1800s who spent years in the Amazon basin, the Philippines, and Taiwan studying the natural habitats of hundreds of species of animals. Today, my home is graced with several of his books, a stunning nautilus shell he collected on one of his trips, and many of his writings.
I attended Central Michigan University, a small state college known mostly as a teachers college, on a partial football scholarship, originally bent on becoming a high school coach and biology teacher. A microbiology course taught by Ellis Brockman, who studied myxobacteria and collaborated with pharmaceutical companies on the natural products they produced, changed that. I took an advanced course with Brockman in which I studied myxobacteria-like flexibacters inhabiting the gills of freshwater salmon, which eventually became part of one of my first publications. In my final year of undergraduate school, I also spent several weeks in Russell Steere’s lab at USDA, doing research that also resulted in a publication. These efforts led me to graduate school at Louisiana State University (LSU) in Baton Rouge, and a PhD under John Larkin studying the biochemistry and ecology of very unusual multicellular, sulfur oxidizing bacterium called Beggiatoa. During my last year of graduate school, I was awarded a Deutscher Akademischer Austauschdienst Fellowship to carry out a year of independent research at the Gesellschaft für Biotechnologische Forschung (GBF) in Baunschweig, West Germany. I left school and spent that year working under the guidance of Hans Reichenbach, an expert in the natural products produced by myxobacteria. At GBF, I got my first significant exposure to the natural products field and to the sophisticated GBF fermentation pilot plant, one of the best outside of industry in those days. After a year’s worth of research that ultimately led to four publications, I returned to finish my PhD at LSU.
In 1980, I was offered a faculty position in Microbiology at The Ohio State University in Columbus, Ohio, to teach biology, microbiology, and build my research lab. Within a year of starting at OSU, I started a fermentation lab to carry out biotechnology research. This led to opportunity to collaborate with Adria Laboratories in Dublin, Ohio, on the discovery of new anthracyclines related to doxorubicin. I translated that opportunity into a new career in natural products, culminating with the elucidation of the 34 biochemical steps for the biosynthesis of doxorubicin, and using the genes encoding those pathways to engineer novel polyketides. For the latter effort, I collaborated with Heinz Floss who was the Chair of the OSU Department of Chemistry at the time. Shortly after our collaboration started, Heinz left for University of Washington in Seattle, where he headed up the Chemistry Department. Nevertheless, we continued our collaboration for many years, resulting in several publications on polyketide and thiopetide natural products. Heinz Floss, who epitomizes the saying, “a gentleman and a scholar,” was perhaps the greatest scientific influence in my life. In 1990, we co-published a paper on the generation of novel polyketides via the manipulation of polyketide synthase genes. This was the first time anyone had mixed and matched polyketide synthase (PKS) genes to form novel natural products. Unfortunately, we did not have the foresight to patent our discovery. Later, several research labs, institutes, and even companies such as Kosan and Biotica, built off of this basic principle to engineer thousands of novel Type I and Type II polyketides via PKS domain shuffling. As a professor at OSU from 1980 to 1997, I was fortunate enough to graduate seventeen Ph.D. students. Many of my PhD students have had great careers of their own, with one a professor at Michigan State and four who rose to VP levels at various biotechnology companies. In my last year at Ohio State, I edited a book entitled “Biotechnology of Antibiotics, Second Edition” (1997; Marcel-Dekker, Inc., New York. 842 pp, ISBN # 0-8247-9867-8), which was widely acclaimed as a leading book in the field at the time. I dedicated that book to my mentors and influential colleagues, Heinz Floss, Arny Demain, and Sir David Hopwood, who helped me to achieve the success I attained as a professor at OSU.
The work on doxorubicin biosynthesis and the genetic engineering of novel polyketides garnered me an offer to join Merck Research Labs in Rahway, NJ, in 1997, to run Natural Products Microbiology. I decided to give industry a try, and upon arriving in Rahway, I quickly hired a group of talented young researchers who could help build next generation recombinant natural products. Unfortunately, just as we started to see success in our efforts to make industrial recombinant natural products, it became clear that the field of natural products was on the downswing. In 2000, I was asked by Emilio Emini, who headed up Merck Vaccines R&D at the time, to start up a bacterial vaccines group. For a year, I headed up two departments, one in natural products and the other in bacterial vaccines. Within the bacterial vaccine group, we also started a phage display effort to support a collaboration with Cambridge Antibody Technology (CaT). Within a year, the bacterial vaccine efforts were moved over to Kathrin Jansen and my group was refocused on making antibodies directed against gp41 to determine epitopes that might be employed for a potential humoral-based HIV vaccine. At that same time, around mid-2001, the Natural Products group was significantly reduced, leaving only a small effort primarily focused on a few anti-microbial programs. I pulled several of my Natural Products microbiology colleagues into a new group focused on biologics within Vaccines Research. We in-licensed the CaT library and began seriously panning against targets for several of the therapeutic areas. In late 2003, we moved the nascent biologics group from Rahway, New Jersey, to West Point, Pennsylvania, to work with a broader array of colleagues from the vaccines discovery group to build on biologics within the renamed Vaccines and Biologics department, now headed by John Shiver. There we built a solid biologics group that worked on several interesting programs across several therapeutic areas. Along the way, we also in-licensed the Morphosys phage display library, several antibody technologies to support the growing programs, and several targets for antibodies. In 2005, we started a collaboration with GlycoFi, who had genetically engineered the yeast, Pichia, to express proteins with human-like glycosylation patterns. Then, in early 2006, a team of us was visiting Abmaxis, a small biotechnology company in the San Francisco area we were considering to acquire for their novel phage display and antibody optimization technologies. After a long day of meetings, we were gathering in the hotel bar to get ready for dinner, when Merv Turner, the head of scientific licensing at Merck, received a phone call that GlycoFi was going up for auction. We debated right then and there whether to enter into the fray, literally using a bar napkin to chart out the advantages and disadvantages of acquiring GlycoFi. Ultimately, in spring of 2006, we acquired both GlycoFi and Abmaxis, with an eye on expanding Merck biologics based on those two platforms. In the eight years I was associated with various Merck biologics efforts, I was personally involved with 16 licensing efforts, as well as being the scientific lead for the two acquisitions mentioned above. Ironically, once GlycoFi and Abmaxis were brought in-house, the biologics efforts at Merck evolved in directions I was personally not happy with, so I began thinking about taking on new challenges elsewhere.
In spring of 2008, I retired from Merck and joined Centocor R&D, a leading biotechnology company that had been acquired by Johnson & Johnson in 1999. When I got to Centocor, I was pleased to find several groups of top scientists working on antibody discovery programs. My job was to bring those groups of excellent scientists together to work with more focus on common goals. That worked out pretty well and in October, 2009, I was named VP of Biologics Research, an integrated biologics discovery department within the newly created Biotechnology Center of Excellence (COE). In December, 2011, Centocor R&D officially changed its name to Janssen R&D as part of a reorganization within the Johnson & Johnson pharma sector to pull all of the therapeutic areas and functional groups into a single unit. Since I arrived at Centocor in 2008, both the biologics headcount and the budget for biologics discovery have grown significantly, due in large part to the recognition of the larger role that biologics needs to play across all therapeutic areas at Janssen R&D. Jay Siegel, who was President of Centocor R&D and is now head of the Janssen R&D Biotechnology COE (as well as head of Regulatory Affairs), has been largely responsible for guiding us into a new era of biologics expansion within Janssen R&D, a process that continues to this day.
In Biologics Research at Janssen R&D, we collaborate with our therapeutic area colleagues to make innovative development candidates that we ultimately hope will benefit our end customers, the patients. Our goal over the next few years is to double our output into development while increasing the innovative and differentiating nature of each development candidate. I am excited to be part of a world class organization that has such broad and deep expertise, ranging from phage display technology on one end of the spectrum to peptide biochemistry at the other end. More importantly, I am proud to be part of a biotechnology organization that has a deep soul, with scientists who display a “get it done” attitude and a love for what we do, knowing that we will ultimately help patients with the novel medicines we are developing. The best exemplification of this occurred in 2009 with the approval by the FDA of two fully human antibodies discovered and developed at Centocor R&D, the anti-TNF-α antibody, Simponi®, and the anti-IL-12/IL-23 antibody, Stelara®. The scientists who discovered and developed those innovative biologics drugs are my colleagues today, and I am humbled to be considered as one of their team. Of these colleagues, Jill Giles-Komar, one of the senior directors in my group, personally led the antibody discovery programs for both of those marketed antibodies.
My personal journey through science continues to evolve. Over the past two years, I have worked with my wife, Lila Strohl, who is a professional medical illustrator, to write and illustrate a book entitled “Therapeutic Antibody Engineering: Current and Future Advances Driving the Strongest Growth Area in the Pharma Industry” to be published in fall of 2012 (Woodhead Publishing Series in Biomedicine No. 11 [Cambridge], ISBN 978-1907568374). The most important lesson I have learned from writing this book is that we will face incredible challenges in biologics discovery over the next decade, and it has helped me to focus our strategies at Janssen R&D to face those challenges head-on. I would not be where I am today without mentors, friends, students, colleagues, and foremost, my wife of 25 years, Lila, who have guided me, advised me, and helped me navigate the course of my multiple careers. Many of them are mentioned in this narrative. Like CD34+ hematopoietic stem cells exposed to cytokines and growth factors developing into myeloid progenitor cells, then into monocytes, and later into tissue macrophages, I have morphed from a student of microbiology fascinated with unusual microorganisms, to a professor of microbiology and biochemistry generating and studying novel recombinant natural products, to an industrial natural products microbiologist, and finally to a leader in antibody and biologics discovery. The pathway has been full of twists and turns, good decisions and bad decisions, smart moves and not-so-smart moves, but like the tissue macrophage, I still have much work to do. .
Figure 1. About Dr Strohl: Dr William R Strohl studied Biology and Chemistry at Central Michigan University (Mount Pleasant, MI, USA), and received his PhD in Microbiology and Biochemistry from Louisiana State University (Baton Rouge, LA USA) in 1980. Dr Strohl then joined Ohio State University (Columbus, OH USA) as Assistant, later Associate and Full Professor for Microbiology and Biochemistry. In 1997 Dr Strohl moved to Merck Research Laboratories as Senior Director, later Executive Director with responsibility for various functions including Natural Products Microbiology, Biologics Research and Vaccines. In 2008 Dr Strohl joined Centocor Research & Development (now Janssen R&D), one of the Pharmaceutical Companies of Johnson & Johnson (J&J), as Senior Director and Head, Antibody Drug Discovery; since 2009, he has been Vice President and Head, Biologics Research, at Janssen. At Ohio State University, Dr Strohl pursued the molecular biology and biochemistry of polyketide biosynthesis pathways, in particular doxorubicin, in actinomycetes, and the physiology of E. coli in computer-controlled high-cell-density fermentations. During his time at Merck he started a new department in the field of recombinant monoclonal antibodies (mAbs), and was a leader in Merck’s efforts to discover therapeutic mAbs, as well as in-licensing of therapeutic targets and technologies associated with mAbs. At Janssen Biotech, Dr Strohl leads different successful antibody discovery programs, which have resulted in several new large molecule early development programs in inflammation and oncology. Dr Strohl’s research has resulted in more than 120 publications in peer-reviewed scientific journals and several patents in the field of pharmaceutical drug discovery and development of therapeutic mAbs. He has edited and contributed to many books and Special Issues related to microbiology and biotechnology. Dr Strohl is a regular speaker at national and international scientific conferences, and an active member on many committees and boards, such as the Board of Directors of the Penn State Biotechnology Program and the Phacilitate Meetings Advisory Board.
