Print BCTV: Touching Patients -- How Duke's Rob Califf; QB3's Reg Kelly go beyond the ivory tower

Touching Patients

Transcript of BioCentury This Week TV Episode 123




Robert Califf, Vice chancellor of clinical and translational research, director of the Duke Translational Medicine Institute (DTMI) and professor of medicine in the Division of Cardiology at Duke University Medical Center

Regis Kelly, Director of the California Institute for Quantitative Biosciences (QB3)



Duke University, Durham, North Carolina

David Murdoch, entrepreneur and owner of Dole Foods Inc. (NYSE:DOLE), Thousand Oaks, Calif.

National Institutes of Health (NIH), Bethesda, Md.

Francis Collins, NIH Director

University of Pennsylvania, Philadelphia, Pa.

University of California, Berkeley, San Francisco, Santa Cruz

ACT UP Advocacy Group



Steve Usdin, Senior Editor




STEVE USDIN: Back to the future, how scientists are getting out of their labs and returning to the real world of medicine. I'm Steve Usdin. Welcome to BioCentury This Week.


NARRATOR: Your trusted source for biotechnology information and analysis, BioCentury This Week


STEVE USDIN: Transformative advances in modern medicine came from physician/scientists with one foot in the lab and the other in the clinic. But the complexity of science has caused many researchers to lose touch with patients. Today, we'll hear from two leaders who are working to bring science back to a future where patients and physician researchers work together.


Robert Califf directs a 30-year collaboration between Duke University scientists and the residents of an entire town, Kannapolis, North Carolina. Together, they aim to redefine disease. On the West Coast, Regis Kelly directs QB3, rooted at the University of California, and aspires to help young scientists break out of the ivory tower and create biomedical startups.


Regis Kelly will join us later on the show. First, I'm pleased to be joined by Robert Califf, a cardiologist and Director of Duke University's Translational Medicine institute. Rob, I wanted to ask you about the Murdoch study and what your goals are, what you're trying to achieve with it.


ROBERT CALIFF: Well, we were at a phase in our university where we're realizing that what we've been calling particular diseases of one kind or another really need to be re-characterized by their molecular makeup.


So you look at someone, for example, with arthritis and their clinical manifestations that doctors have used for decades to call it one type of arthritis or another. But we began to realize that with fancy, special genomic technologies what was characterized as one disease may, in fact, be five or 10 different diseases that should be treated differently.


So as we began to look at this, we were looking for a way to get a population of people to involve them in a study and to follow them over a long period of time. And along came a gentleman named David Murdoch who is an entrepreneur, the owner of Dole Foods, very interested in healthy lifestyle and healthy people.


He had a history in the Southwestern part of North Carolina. A place called Kannapolis or Cabarrus County, North Carolina. And he approached us with the idea of starting a biotechnology center in Kannapolis, North Carolina, and then endowing a population study where we would enroll people and then follow them over time and collect specimens so that we could uses this genomic technology to classify people according to the diseases that they had.


STEVE USDIN: So you're really taking, basically, almost as many as you can, as much as you can of the adult population of Kannapolis and putting them under a microscope-- or not really a microscope, you're putting them under a gene sequencer. And you're going to study them and their changes in health status over long periods of time.


ROBERT CALIFF: That's correct. And, of course, this is a very hard thing to get funded, for example, by NIH now because of the budget. It takes a long-term study. Industry would be interested in this, but typically wouldn't fund a 30-year study.


So we're really lucky that Mr. Murdock came along. He was excited about doing this. And you're exactly right, It's about 170,000 or so people. We're going to collect data on about 50,000. So about a third of the people that live there.


And using electronic health records, we're going to follow them as long as we possibly can.


STEVE USDIN: So one of the things that's interesting that might come out of something like this, I imagine, is that you'll have the ability to predict what's going to happen maybe even on an individual basis to people who are living in Kannapolis based on the data that you're getting. Is that realistic?


ROBERT CALIFF: I think it realistic to make a prediction. Of course, I think predictions will always be like the weatherman. I mean, we know weather predictions are getting better and better and more proximal. But you still get a probability. No one can tell you exactly what's going to happen to you, except maybe God.


So we live on probabilities. We want to make those probabilities better.


STEVE USDIN: And you talked-- we started out, you talked about kind of redefining diseases. I've seen also that you've written that you expect this study to rewrite the textbook of medicine. That's a very ambitious goal. How do you get from here to there?


ROBERT CALIFF: Well, it's a little bit of a play on words, obviously. But when I was a medical student back in the '70s, we were just beginning to develop computerized databases. To young people, this sounds very strange-- before computers, who could imagine?


But the idea was we had these textbooks that we all live by in medicine. There were these tomes of written documents. With a living database, with a computer, you're rewriting the textbook as you go.


So it's taken 30 years to get there. But I think we're now in an era where that's really going to happen. Just take something you would take for granted like osteoarthritis. A common problem. You might say not that important until you realize that there are tens of thousands of hips and knees being replaced every month in the United States.


So if you had osteoarthritis at age 50, are you're just going to have sore knees for the next 30 years? Or are you going to go on rapidly to need a mechanical replacement, which is very expensive and carries risk?


And if you could make that prediction of who's really at risk and who's going to just have a mild manifestation of the disease, you could intensify the prevention and the treatment of the people who are really at risk. And I think we now are going to be able to do that. It's going to take time.


STEVE USDIN: One of the things that the Murdoch Study reminds me of, it's reminiscent of the Framingham Study, which changed the way people think about heart disease. What are the similarities/differences between what you're doing and the Framingham Study?


ROBERT CALIFF: Well, first of all, we have to pay homage to the Framingham Study. Sometimes our people get a little enthusiastic and call us a modern Framingham Study. Not realizing, of course, the Framingham Study is still going on, and it's been continuously modernized as it's gone on. The Framingham Study can't be replaced.


But what we are doing is taking a broader look at all diseases in a large, somewhat more heterogeneous population. And what's particularly different, it just so happens this area of North Carolina is what's called a beacon community, designated by the federal government because of a very high penetration of electronic health records. Which it's beginning to happen everywhere, but they've had it for a while.


If you think about the cost of research, if you have to see people back once a year and collect a whole bunch of data, it's very expensive. But if you can harvest data from the electronic health record in a collaboration-- and I think this is another important point. This is not research we're doing on people.


The people of this county are involved in the research. They are participating. And they're contributing their information together with their doctors into our electronic database.


STEVE USDIN: That's interesting. They talk about collaboration and electronic medical records. When we come back, we're going to talk about another ambitious effort to try to integrate clinical research with clinical care and collaboration.


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STEVE USDIN: We're back with Doctor Robert Califf talking about merging academic research and clinical care. Rob, you're the principal investigator for the coordinating center for something that's called the Collaboratory. Can you tell us what that is?


ROBERT CALIFF: Well, I mean, who wouldn't want to work with something called the Collaboratory?


STEVE USDIN: It is a cool name.


ROBERT CALIFF: It's a great name. So the Collaboratory is an effort to move clinical trials into an era where we use electronic health records in the context of clinical care as a backbone of data collection for the clinical trial. It sounds pretty simple, but it's very complicated. The story behind this is-- of course, many of us have been thinking about doing this for a long time.


But we're now finally at the point where the technology is where it needs to be. The NIH began to think about this. And they have a thing called the common fund. The common fund is designated for the director of the NIH, in this case, Francis Collins to use, to do projects which are high risk, cutting edge, and wouldn't be done by any single institute within the NIH. Because all the institutes in the NIH are disease-specific like heart, lung, and blood, cancer, et cetera.


In this case, this is a project that cuts across all the institutes. It's funded by the director's office. And it's meant to last five to seven years. And if it succeeds, it will then become part of the regular NIH funding stream. If it fails, it'll go away.


STEVE USDIN: And Collaboratory suggests that there's an element of collaboration here. What are the parties? Who is it that's collaborating?


ROBERT CALIFF: Well, what the NIH did-- and one of the interesting parts about this, the way the common fund works is a bunch of grantees get together for several years and sort of have a competition for ideas about what's most important to do. And it gradually filters up to the NIH director. He or she makes the decision about what's going to get funded. And then there's a plan to do it.


So what the NIH did was, they said, let's have a coordinating center. The roll of the coordinating center is to distill generalizable knowledge from the clinical trials that are being done, and also to help the clinical trials get done. Now what are the clinical trials?


Clinical trials come from individual groups who've submitted applications in a very competitive peer review-- over 80 applications, seven trials got funded. And our job is to get them all to work together because this is a new area. No one knows exactly what to do. There is a good history, and there are good ideas. But the topics range from-- should you take your blood pressure medicine at night or in the daytime, to suicide prevention, to can you use electronic health records to improve colon cancer screening. So it's like a textbook of medicine. And what we are meant to do is to look across all these projects and pick out the generalizable knowledge, so the next person wanting to do a pragmatic clinical trial can get it done more efficiently.


STEVE USDIN: And when you're talking about a pragmatic critical trial, that's really looking at what's actually kind of a natural experiment, something that's actually happening in the medical system, or something that can do without creating a lot of artificial parameters around it?


ROBERT CALIFF: Right. If we think about the way clinical trials have traditionally been done, you have clinical care happening out here all over the world, then you cordoned off a thing called a clinical trial. You create a separate database. You have a set of rules about what you do. And it's almost like trying to create an experimental laboratory with human beings.


The counter-thinking, which is something I really believe in, is, for many clinical trials, we really want to do them in the context of clinical care. Because when the trial's over, we want the answer to pertain to what would you do with your next patient in real life in clinical care? So the idea here is, it's real-life clinical care, using electronic health records, one of the rules to be one of these clinical trials-- you had to have two integrated health systems, at least, working together.


So it can't just be one group. You've got to work across groups, which means we can now begin to think about very large sample sizes, tens of thousands of people. If you think about 300 million Americans, most with an electronic health record now, you could really begin to do clinical trials very quickly and efficiently this way.


STEVE USDIN: So you basically, you could look at it, and you could say, you could ask a question-- 10,000 people who get this drug for this condition, 10,000 people who get that drug for that condition, what are the differences in the outcomes?


ROBERT CALIFF: That's right. And this is an example of one group. University of Pennsylvania got together with the two big for-profit dialysis companies in the U.S. So it's hundreds of thousands of people getting dialysis every day. What a great context to do clinical trials. I mean, the people show up three times a week. They have to, for their clinical care.


And a very simple question-- how long should the dialysis run be. You'd think we'd know the answer to that. Well, we don't. So they're doing a randomized trial-- there'll be a very large sample size-- to a longer versus shorter dialysis run. And we don't know the answer. So it's a very important question, with many ramifications, both for clinical outcomes, and for costs. So just one example of how this can work.


STEVE USDIN: And how long will it take to get an answer, for example, to that question?


ROBERT CALIFF: Well, one of the interesting parts of this adventure is-- the seven groups that were funded are in sort of a planning phase for about nine to 12 months. And then there's a new starting line where to trial actually begins. And then it should only take one two years to get the answer.


When you think about clinical trials the way they're typically done, now, they're years of planning and then they don't enroll very fast because you have this parallel universe that takes a long time. So we think this will be much more rapid. And if it works, which I think it will, if you think about 200,000 people getting dialysis every day, there are probably 10 or 20 really important practical questions. You could just reel them off one after another.


STEVE USDIN: Thank you, Dr. Califf. We've heard how Rob Califf is working in North Carolina to break life science researchers out of their ivory towers. When we return, we'll meet Doctor Reg Kelly, who's working in California to forge links between universities, businesses, investors, and patients.


NARRATOR: BioCentury this week host, Steve Usdin, named this year's Harvey W. Wiley lecturer by the FDA alumni association. He's the first journalist to receive the Wiley award.





NARRATOR: Now, back to BioCentury This Week.


STEVE USDIN: Reg Kelly directs the California Institute for Quantitative Biosciences. QB3 was created to knit together work being conducted at over 200 University of California labs in Berkeley, Santa Cruz, and San Francisco. It's focused on commercializing academic research, creating a business incubator, and launching a venture capital fund.


I'm pleased to be joined by Reg Kelly. Reg, I wanted to start-- there's a lot of talk. Everybody talks about translational science, and they have different ideas of what it means. For you, it seems to mean coupling academic researchers and the world of business.


REGIS KELLY: You're absolutely right. Many people think of translational research as going from the basic science into the clinical community and back. That's not the way we think about it, because many of the science goes right out to help the public, right out from the scientists right into the community. So what we actually see is-- the way we want to contribute to society is we believe that the constriction in the $30 billion federal investment and government research is not getting out to help the public. And we try to help it get out by starting companies.


STEVE USDIN: So you're saying that there's $30 billion approximately that NIH spends on basic research, and it's somehow bottled up in universities, and you're trying to help it to get out.




STEVE USDIN: When you have a partnership like that when you're bringing together academic scientists and industry, each party has to bring something to the table. What are the unique things that academics bring to the table? Why can't universities, I mean industry, just do it by themselves? And what is it industry brings besides money?


REGIS KELLY: Yeah, it's a good point. What we find is that the academics are really good at coming up with solutions to problems, and they're discovering things, but they're not very sure what the problem is that the solution's to. They've got a widget, they don't know what to do with it. Whereas the industry, our private sector partners, they actually know what the public needs. So when you bring the private sectors with our academic scientists, it's a marriage made in heaven.


STEVE USDIN: And you've got a couple of different ways that you're trying to make these heavenly marriages, right? So, one of them is that you're trying to create entrepreneurs or help scientists become entrepreneurs. Can you teach entrepreneurship?


REGIS KELLY: Yes. Yeah. You don't have to teach innovation. People just innovate all the time naturally, but trying to teach how you can take an innovation and make it practically move forward through the steps ready to make it into something useful, you can teach that fairly easily.


STEVE USDIN: And you do more than just teach, right? You actually hold people's hands and nurture businesses.


REGIS KELLY: You're right, yeah. We have a program we call Startup in a Box, because most of the people we find stocking companies are graduate students from post-docs who don't know much about business. So we help them, we get them free legal help, we teach them how to incorporate their companies. We do all the sort of messy stuff for them so they can focus on their science.


STEVE USDIN: It's interesting that you talk about graduate students and post-docs, because we had Dr. Francis Collins, the director of the NIH, on the show, and one of the things that he described as a problem is that there's a mismatch in the educational system-- that there were far more post-docs created than there actually are tenure track positions for them to be in. Is what you're doing-- can that address some of those workforce issues?


REGIS KELLY: It's not the complete solution, but it's certainly helps solve the problem. You're quite right. Every faculty member will train about 50 students during a lifetime. That's a huge family. It's impossible for the whole system to continue this way. What we do then is for many of these really bright young people, we actually help them to take their talents, their creativity, and start companies with that rather than feel that they have to get a university job.


STEVE USDIN: Reg, I wanted to ask you about the venture capital firm that QB3 has started. What's its purpose? Most people think of a venture capital firm is to try to invest in something and get outsized returns for their investors. Is that what you're venture capital firm's aiming at?


REGIS KELLY: No, we started this-- there are plenty of venture firms out in Sand Hill Road in San Francisco. They don't need another venture firm. What we wanted to do is to come in down in the weeds-- to go in to invest in very small amounts, early seed funding, in companies that were so small that big venture companies were not interested in. So we were coming at this very market, so we invest at about the half million level.


STEVE USDIN: So it's almost like microfinance in the developing countries.


REGIS KELLY: You got it. Yes.


STEVE USDIN: And then once you've done that then, how does it get to the next level? Do these companies have success in attracting the Sand Hill Road venture firms?


REGIS KELLY: Yes. So we very much want-- this is a commercial thing. This isn't a philanthropy. We've got to make money. Our limited partners have invested in us, and we are trying to return profits to our limited partners on this. However, there's 20% of the profits come back to the general partners, who are me, and I turn that over to the university, because I'm a university employee.


STEVE USDIN: And what's your time horizon? That's one thing when venture capital firms are investing, they are looking at a particular time horizon for getting their returns.


REGIS KELLY: Yes. The way it normally works-- and we will try and follow the same model-- is show that we've invested in 10 or 12 very successful companies by four years into this. We're two years into it right now. Then we go out and raise our second fund, and usually you can raise a second fund before the liquidity events on the first.


STEVE USDIN: How big is your-- how big is the fund?


REGIS KELLY: Our fund currently is $11 million.


STEVE USDIN: And you're saying about a half million dollars that you're investing--


REGIS KELLY: Yes. We have about nine companies we've invested in so far.


STEVE USDIN: Do you have any co-investment in the--


REGIS KELLY: Yes, we have co-investors. I'd say several of the big pharma companies want to co-invest in us, because they are trying to get in very early into the markets. And we've done due diligence and derisked the companies, so they co-invest.


STEVE USDIN: So that's interesting. So you're kind of-- in a way, you're proving the concept or you're getting kind of a stamp of authenticity for these companies by investing in them.




STEVE USDIN: Can you give any examples of some of the companies that you've invested in?


REGIS KELLY: Yes. One of the companies is trying to make sure when you take a drug-- you know very often it gets cleared out of your system really quickly, especially if it's a protein. So they've got a ways of modifying the protein so it can stay around in your blood for many times longer than it would normally.


STEVE USDIN: Starting a company is one thing. Starting a successful company or a company that prospers is quite a different thing. What's your track record there, and how do you know whether companies have graduated?


REGIS KELLY: Well, let me go back a little bit. The companies that come into our incubator, we don't subsidize them at all. They've got to pay their own rent. So this is a way of showing that there's fire in people's belly. They've actually gone out and find someone who will pay the couple of thousand dollars necessary for rent each month. Then actually as long as they do that, we let a thousand flowers bloom, because it's very hard at a very early stage to know whether a company has the correct combination of idea, market, management to succeed. So let everyone try, but let them try at a very low cost.


STEVE USDIN: Thank you.


QB3 has helped create companies and jobs, but what impact will it have on health? We'll talk with Reg Kelly about measuring QB3's effects on medical innovation when we return. First, some stats on QB3's economic impact.




STEVE USDIN: We're back with QB3's Reg Kelly talking about commercializing academic research and how it can benefit society. Reg I want to ask you. We just saw some statistics about the numbers of startups that QB3 has helped to create. But are there other ways to measure or to think about the success of what you're doing or the importance of it?


REGIS KELLY: Well, let me just say why am I involved in doing this. I came out of retirement to do this. I really believe that if we want to take advantage of all this government investment, this is really the constriction point. This is actually what's slowing down the development of drugs.


And let me give you a personal story on this. My wife has Alzheimer's. She was a brilliant scientist. Also, she worked for Stanford Research Institute. She got Alzheimer's five years ago.


Because I'm connected to the pharmaceutical industry, I'm able to go around and see where is there some really great new drugs that are going to cure Alzheimer's. I can say there's nothing that's very impressive in the pipeline.


So what is going to happen here? People are saying there's problems in the pharmaceutical industry. Oh, what a problem that is. But for those of us who are watching people with Alzheimer's fall apart every day, this isn't about the money. This is about we've got to make the system work better. And it's not working well right now.


STEVE USDIN: And so there's the sense of urgency that's impelling what you're doing. It's not just academic and it's not just economic development.


REGIS KELLY: I am certainly not in it personally for the money. The money is just the way you make it happen. It's not to make money. It's just to lubricate the process.


STEVE USDIN: So you mentioned your wife. And everybody has been touched by the disease. I have a sense that patients and patient advocates can play a role in creating these linkages between universities and industry. Do you think that's realistic?


REGIS KELLY: That is very realistic. In fact, my wife is a very powerful advocate for Alzheimer's, because she actually helped develop the vaccine that she got in a clinical trial.


And what she realized, the best thing she can do with her life is to try and make Alzheimer's Association behave like ACT UP, because ACT UP got drugs through for AIDS very effectively. So patient advocacy groups are crucial in moving forward and getting through the blockages in the pipeline.


STEVE USDIN: And that's really interesting, because what surprises me continually is that there isn't that kind of advocacy. There's isn't that kind of passion and demand and urgency for change like the AIDS activists had. Why do you think that it?


REGIS KELLY: I think it's because it's embarrassing to expose yourself. The big sacrifice AIDS people made in ACT UP and so on was to go out and say, look, I have the disease. They didn't try and hide.


When you're old and you're stuttering and you can't remember, you're embarrassed and you don't want to go in front of people and show off. So people are afraid to go and advocate, because they don't want people to laugh at them. And so people have to be willing to let their infirmity show in order to get public support for the disease.


STEVE USDIN: Thank you. That's this week's show. Thanks to Reg Kelly and Califf of Duke University. I'm Steve Usdin, and I'll see you next week.