Adam Kuspa, Ph.D.
Adam Kuspa, Ph.D., senior vice president for research and professor of molecular and human genetics at Baylor College of Medicine, sat down with Texas Medical Center Executive Vice President and Chief Strategy and Operating Officer William F. McKeon to discuss a renewed focus on collaboration and commercialization, and how an exciting joint venture could help open new doors in medical genetics.
Q | I want to hear about your early days growing up in California…
A | I grew up in a small beach community, north of San Diego, surfing and skateboarding. In junior high, I became interested in biology. I was inspired by a very dynamic high school biology teacher who had a master’s and whose husband was a professor at the University of California, San Diego. So from a very early time, I guess the ninth grade, and being five miles from one of the great research universities, I just assumed I would go in that direction, and sure enough, I did.
Immediately I wanted to do bench research, so I latched onto a laboratory, run by Bill Loomis who had a very infectious enthusiasm, and who really cared about what people did in his lab. It seemed like a great place to work, and it turned out it was. The focus of his lab was developmental biology, using the social amoeba as a model.
Very quickly, I turned into a lab rat. College classes became secondary, and I was usually running out of the lab arriving late to my lectures, and then running back to finish my experiments. I published a paper and was thinking about going to grad school when Bill Loomis advised me to think about the Stanford Biochemistry Department, which was one of the great departments of that era. It had a small number of faculty, but they were all excellent and each of them cared about training future scientists. I did okay in college— Mostly As. But I didn’t think I had a shot at getting in a top graduate school. I remember asking one of the postdocs in the Loomis lab about it. I said, ‘You know, Stanford biochemistry gets 400 applications and they take four students. What are my chances?’ And he looked at me and said, ‘You only need one slot.’
So I applied and got in. Training at Stanford was a transformational experience. You don’t really realize it when you are in the middle of it, but looking back—10, 20 years later—you realize. I was discussing and debating scientific concepts with the folks who would be the leaders in American science for the next 40 years, and sure enough, almost every person that I interacted with in that department 20 years later was in the National Academy, or a department chair, or a professor at MIT, Harvard, and so forth. The intellectual atmosphere was so enriching and so exciting, you couldn’t wait to get to work. You couldn’t wait to interact with your colleagues.
And that’s why I’m here, actually. I did a postdoctoral period back at UCSD, the same where I was an undergrad with Bill Loomis. It’s just hard to find a mentor who is just as interested in every single experiment as you are and who wants to discuss things with you every day. It’s hard to get that kind of mentorship and support.
I did a lot of good things with him, but when I was looking for jobs, I thought I would do a little preliminary job search—just a limited number of applications. I didn’t think I would get a job. But I ended up interviewing at 11 different places, and had three offers: Duke, here and the University of Connecticut. And The Texas Medical Center and Baylor College of Medicine just instantly felt like Stanford. I just walked the hallways and could instantly sense the same kind of collaborative spirit. It’s what they told me in my interviews here, ‘This is a really collaborative place!’ One might think they are just trying to sell you on the place, but you could just feel it in the way people seemed to genuinely care about what everyone else in the place was doing.
I think it’s about the faculty. And I think that’s true across the medical center. Just consistently attracting people who are not so egotistical—to the exclusion of everyone else—but they are genuinely interested in science and biomedicine. They are just genuinely collaborative. And it’s a spirit that has been maintained throughout my 21 years here. And you really learn about the robustness, about academic structures, when you go through the economic downturns. You know, we are just coming out of 10 years of rough financial times, since losing our primary affiliation with the Methodist Hospital System.
What I learned in this time is the robustness of the academic enterprise, being rooted in the faculty. Our faculty members didn’t waiver, and not that many left. They just put their noses to the grindstone and kept getting the grants and driving their programs forward, in spite of the financial challenges. And that’s what carried us through—on the research side, on the education side, and on the clinical service side. It was a great thing to witness.
Q | Collectively, the research engines on this campus are number two in NIH grants—second only to Johns Hopkins. Is there also a compendium effect of having these other institutions on the same campus?
A | People think we are hyper-competitive, and maybe we are on the private clinical side. But in research, the TMC is one of the most collaborative places in the world. Our faculty members collaborate with every other institution equally well. There are few boundaries or feelings of antagonism or competition. And we have lots of cancer folks—about a quarter of our research is in cancer—and yet there are substantial collaborations between MD Anderson and Baylor in research and education. There is a huge amount of collaboration between Rice and Baylor, of course. So the TMC really functions as one big research ecosystem. Sure, at the executive level there is some friction about the movement of faculty, or programs, but even there it is becoming more collaborative.
There is sort of a renewed spirit of collaboration around commercialization, and that’s very healthy. I think that has also spurred on the collaboration around the research cores, and sort of a shared interest in trying to make all of the resources of the individual institutions available to everyone. This is all funded by either public money or local philanthropy. I very much view the whole TMC enterprise as a communal endeavor, and Houston is competing with the rest of the world.
Q | As you are responsible for all research at Baylor, how do you find the time to conduct your own research?
A | Some people would call what I do now vanity research, because although I have a federally funded lab, I can only actually physically be in it about four hours a week. I have to fit my manuscript and grant writing in at nights and on weekends because I have at least eight hours of meetings every day, plus ‘home work’ stemming from my role as senior vice president.
Q | Is that hard for you as a dedicated researcher?
A | Most folks in my position live with a conceit that they will eventually go back to the laboratory. And seeing that Harold Varmus did, after running the NIH and the National Cancer Institute, go back to running a lab at Cornell gives me hope. You see this kind of example and think, ‘That’s me! I am going to go back to the lab eventually.’ I worry a bit about losing the possibility of going back to research full time and I worry about maintaining credibility in my field. Having said that, I love what I do now.
When they asked me to interview for the chair of biochemistry, I had no thought of going into administration, although I was program director for the graduate program for 10 years prior. I had enjoyed helping students and mentoring students and making sure they were taken care of and that they were in laboratories that were best for them, and that they were progressing toward their degree. I knew I enjoyed mentoring students, but I was not sure I would enjoy being chair of biochemistry. However, I found that I really loved it. Just as a lab head worries about how their postdocs and students do in the lab, as a chair you worry about how your assistant professors do; you mentor them, read their manuscripts and their grants and try to give them advice that will advance their career. I found that I really loved the chair role. When they asked me to come downstairs, I thought, ‘Well I liked organizing science at the department level, let’s see how it would be at the college level.’
I was appointed by Bill Butler, who was the interim president at the time. I quickly learned that being a corporate officer, a fiduciary of the institution, is very different from being a department chair. There was a steep learning curve. Paul Klotman, the current president, came just a few months after I was appointed, so it wasn’t clear at all that I would be continuing. One of the first conversations I had with Paul was along the lines of, ‘You don’t know if you want me to be dean of research, and I don’t know if I want to continue to be dean of research. So let’s talk in six months.’ He agreed and about six months later, February 2011, he asked me to stay on and I have been doing it ever since.
I wondered initially whether I could have an impact and help to guide the institution in research. No one is irreplaceable and I knew that if I were unable to do this, I would step aside. But it has been very rewarding, interacting with the leadership at other institutions within the TMC and around the state. Trying to develop programs within Baylor and with other institutions. Under Dr. Klotman’s leadership, the executive team has been trying to effect the kind of change that I think most people would agree needs to happen in science today. We need to operate more efficiently, develop new sources of funding to drive program development, while still allowing the faculty to drive the science and set the direction. That’s what we are trying to do.
Q | What do you see changing over the next five years, relative to the research program at Baylor?
A | From a technical management point of view, we are working towards becoming more service-oriented around clinical trials. Clinical research in terms of reaching outside the institution. We have a pretty big operation: 4,000 human subjects protocols, 11,000 patient accruals a year, with about 4,000 of those having therapeutic intent. But our support infrastructure is pretty decentralized. This is not necessarily a bad thing, but if you want to present a positive, user-friendly face to the outside world, if you want interact productively with industry more, it requires that you centralize resources and have master agreements that don’t have to be negotiated independently for every trial. This is an operational improvement that we would like to make.
On the scientific side, we are paying more attention, and allocating resources, toward taking our basic science toward the clinic. That’s not an original idea— everyone is tying to do that. But we have been a great basic science research institution, so this is a change in direction. We used to joke that we discover a drug target every week, but we don’t do anything about it. And that certainly was true 10 years ago and even five years ago.
We spend $400 million a year on biomedical research and yet we did not have much in the way of drug development or other experimental therapeutics. We have sort of been on both ends of the research spectrum; third-party clinical trials on the one side, basic science on the other and not that much in between.
We are trying to bring forward that opportunity at several levels. We are hiring chemists and developing a center for drug discovery so that we can bring forward small molecule therapeutics. We are building the support structure that would allow that to happen. In terms of pilot projects, we have the opening of an Innovation Development Center, and other commercialization efforts. We are trying to pull the most promising projects out of the lab and put them along a critical path towards some kind of therapeutic or diagnostic outcome. We are just getting started, so it is too early to judge our efforts. But it has been a lot of fun.
Q | Do you believe the multi-institution institutes like Innovation and Clinical Research will serve as a springboard for the next generation of discovery and commercialization?
A | Yes, I can see a future where all of the institutions interact robustly on the scale of the TMC, in much the way you have laid out in your innovation programs. That said, I don’t see the individual efforts of the TMC institutions going away. I only see them strengthened. Because the larger entity—the interaction with the third parties, big pharma, and so forth—they will not want to develop every single project that comes out of all of the institutions. The institutions will want to ensure that their own individual projects have the maximum impact through their own natural course of development.
I have seen enough of these projects now, just going back five years. I started as a chair of biochemistry with one particular small molecule therapeutic starting in 2005, and am seeing how it is only now getting to phase one clinical trials over a 10 year period. These things have such a circuitous root. On the one hand, you wonder if it can only come to fruition in an academic setting. This project could have been shut down five times over if it was in industry, and it may have been rejected in a TMC-wide down-select process. But there are going to be these projects that individual institutions believe in. For whatever reason—the specific need that is being addressed, or the particular faculty member, or whatever set of criteria they have in their own institution—they will want to be able to drive that forward, independent of other exigencies. So I see that going forward we will have a hub-of-hubs sort of model of innovation. There will be hubs at the institutions whose projects may feed into the TMC program or be developed independently.
Q | Someone once told me that on the east and west coasts, they worry most that the Texas Medical Center member institutions will actually come together programmatically, and in doing so, will become the dominant force in discovery and commercialization. Is that all talk, or do you believe there really is an opportunity here?
A | I believe this 100 percent. The strong research institutions in the TMC are fully onboard and this will be a very attractive center in the coming years. The turnover in the leadership of all of the TMC institutions has really changed the culture toward commercialization. This is not just to generate revenue to support our missions, but to maximize the impact of what we do. The Baylor Miraca Genetics Lab is a great example of this.
Q | Tell us more about that. I think it is a perfect example of something that has grown out of research and became a service that grew into a business.
A | It started in the early ‘70s, with Tom Caskey and Art Beaudet starting to see pediatric patients with odd biochemical anomalies that they could trace back to a genetic cause—an inborn error in metabolism. That led to a more robust formulation of a biochemical genetics laboratory and collaboration with Texas Children’s Hospital. The unique features of this from the late ‘70s, when this was formalized and growing into the arena of molecular genetic diagnostics, were: patient volume; our world-class genetics department that was built over decades under Tom Caskey and, later, Art Beaudet; and the national Human Genome Sequencing Center under Richard Gibbs. Those three things together led to this unique opportunity to drive innovation in clinical genetic diagnostics. Art Beaudet saw this and started pushing the model of an academic reference lab, the Medical Genetics Lab (MGL), that would continually innovate and would be essentially forcing the conversation around the clinical utility of molecular genetic diagnostics. They would typically offer a test before most doctors knew it would be useful, and offered it to the academic physician scientists who had patients with complex cases with a suspected genetic component.
In the late ‘90s, early 2000s, the vision was to replace karyotyping by chromosome spreads with chromosome microarrays. So we were the first to launch that commercially, and it was a spectacular success. For the first time you were able to diagnose not only large chromosomal rearrangements and trisomies, but also small deletions and duplications by basically reading a chip. The uptake of that was tremendous. It drove revenues for quite a while. So it developed into a $40-50 million a year revenue business. The latest innovation involved bringing Richard Gibbs and his team on board to create the first clinical whole exome sequence test. They were the first to launch a whole exome test in 2011, doing about 200 cases a month, with a 26 percent diagnostic rate. For you and I, having lived in the days in the mid-‘80s when the suggestion that we would sequence even one human’s genome was thought to be science fiction, this is remarkable. The thought that we can sequence the relevant genes of a patient over a few week period and then interpret the clinically relevant genetic variants and return a diagnoses back to the patient really truly seems like science fiction.
Q | Any closing thoughts?
A | There are intense pressures on how academic medical centers are being funded and have been funded in the past. I think the public does not understand the threat that the TMC institutions face. Our institutions are where the innovative new medical treatments are developed and they are an invaluable national resource. The traditional fee-for-service medical revenues cross-subsidize our education and research programs, and they are under pressure and rapidly changing into a new model of medical care delivery. I view this generally as a good development, but it presents a major challenge for the next five to 10 years. We have to morph our old academic medical center model, with the traditional sources of support, into one where we develop new sources of support through carefully thought-out joint ventures and bring commercial funding into the mix in a meaningful way. To the extent we can align incentives between commercial interests and academic priorities, this should work. I think we have to take advantage of the market forces in biotech and pharma to drive what we do in better ways than we have in the past. I have spent the last five years making this argument to our faculty and they have responded positively, but it is too early to judge the outcome of our hospital joint venture with CHI, or our diagnostics joint venture with Miraca. And we have other JVs in the works. We are trying to leverage our unique capabilities in research into some sort of a commercial format that brings a unique opportunity to an outside venture but also brings a unique opportunity to support the academic enterprise.