Butte on the Pursuit of the Ultimate Source Code of Humanity

; Atul Butte, MD, PhD


April 13, 2015

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Seeking the Ultimate Source Code

Eric J. Topol, MD: Hello. I'm Eric Topol, editor-in-chief of Medscape, and I have a very exciting One-on-One session with Atul Butte who has moved from Stanford University to the University of California, San Francisco (UCSF). He will lead the Institute for Computational Health Sciences. Atul, it's wonderful to have a chance to visit with you.

Atul Butte, MD, PhD: It's great to be here at the Future Genomic Medicine Meeting.

Dr Topol: You are a veteran, having been here before, but your work has been quite extraordinary. Let's talk about your background as a pediatric endocrinologist and also as a computational scientist. How did you get into both of these fields?

Dr Butte: Back in high school, I knew that I liked computer science and medicine. I thought I would grow up to be a radiologist. At the time, the cover of National Geographic had this technology called "MRIs" and "CT scans," and then while I was in medical school, the genome project started. I realized that to figure out the ultimate source code of humanity was what I wanted to do. This was back in the early 1990s.

I trained as a pediatrician, because to me pediatrics is closest to genetics. Pediatric patients don't do much to themselves; it's all genetics. Then I ended up training some more, and I have been at Stanford for 10 years. Now I am moving to UCSF.

Academia's Role in Changing the World

Dr Topol: Tell us about the 10 years you spent at Stanford. What were you able to accomplish during that decade?

Dr Butte: I started on that first day with a career development award—one of those K awards that we all look for as junior faculty. I'm ending with a team of 30 people. We have published 200 papers and have received 15 or 16 National Institutes of Health (NIH) grants. I'm not saying this to brag, but to tell the junior faculty of the future that it is possible to do this. It's possible to change the world by sticking with academia. I'm still a huge fan of academia; that's why I am remaining an academic when I move to UCSF. It is a harder climate today, but I think it's still about changing the world. The NIH recognizes that. It's possible to do it.

Dr Topol: When I think about big data and medicine, you come to mind, but you probably were thinking big all along. You had a big vision about where you could take this, right?

Dr Butte: Today's term is "big data." Whether you call it "precision medicine," or "computational health," they mean the same thing—first-line medicine. Medicine is becoming more computerized in a data sense.

There are two big drivers. At this meeting, we are talking about the genome and the genome project. A lot of bytes are being measured there, but in medicine we are also recording more of the things that we do or are measuring from patients on electronic health records. The collision or synergy between those two is an exciting place to be.

Dr Topol: When you start at the new institute, will it be tough to leave everyone behind at Stanford, or are you taking some of them with you to UCSF?

Dr Butte: I am hoping to take all of my team, plus or minus a few who have to stay for commuting reasons. I am hoping to take all of them.

To be clear, I was not unhappy at Stanford. I was thrilled. It's just that UCSF has a lot of senior leadership who understand this phrase "precision medicine." They are involved with the Institute of Medicine's plans for precision medicine. Even 4 years ago, Keith Yamamoto and Sue Desmond-Hellmann, who has now left to be part of the Gates Foundation, were part of this recruitment. This recruitment has been going on for 4 years. I see a new building being created around computational health, and a lot of future potential.

A Home for the Big Data

Dr Topol: Where is this field going, at UCSF and on a much bigger scale? We are going to be generating a terabyte of data per individual. We are going to have sensors for blood pressure, and for every heartbeat. There is no home for these data. How are we going to work out all these problems?

Dr Butte: The future is going to be complicated, before it becomes simpler. We will have millions of pieces of data on millions of individuals. This morning at the meeting, we heard Francis Collins talk about cohorts of volunteers across America. UCSF will be a part of that. We have 12-13 million patients at the University of California (not just at UCSF, but University of California-wide) who would love to be a part of this effort. That's part of the reason I am moving. Individuals are able to take more measurements on themselves, whether it's their sleep patterns or heart rates.

I don't think data are going to live in any one place, but across different places. Different places are going to want to get to those data. Patients and individuals will have more control over their data (eg, how to share their data), and medicine has to move faster, and data will be the solution.

Dr Topol: You are leaving a private university—Stanford—which is also known as Start-up University.

Dr Butte: That's right.

Entrepreneurship: Not About Getting Rich

Dr Topol: It's quite a breeding ground for entrepreneurship. You have started a couple of companies. Now you are going to a public university. Do you have any qualms about that?

Dr Butte: I have no qualms at all. In fact, in terms of entrepreneurship, UCSF is up there. It's a little bit more institutionalized. Reg Kelly has been working on something called "QB3" for more than 10 years now—an effort between UCSF, University of California at Santa Cruz, and Berkeley. The building next to where I will be has incubator space for these companies at UCSF. A number of other companies, such as Johnson & Johnson and others, have already built buildings around Mission Bay to incubate some of these biotech and tech companies.

I'm not looking at less entrepreneurship; I'm looking at more entrepreneurship there. I keep mentioning entrepreneurship not because I'm trying to get rich, but because my lab believes that if we want to change the world, we can't just keep writing papers about it. This is how we are going to get it to patients.

Dr Topol: That's quite an important message to get out. You formed one of these companies with your wife, is that right? Can you tell us about that?

Dr Butte: The company is called NuMedii. My wife and I, and now others, are part of a company on drug repositioning—finding new uses for drugs. We all know the classic stories about cardiac drugs with interesting side effects that become such drugs as Viagra®, and minoxidil for baldness. Instead of finding these new uses by accident, how about finding them on purpose? How about finding them using public big data, the kind of huge efforts that NIH is funding in labs? That data have to be shared on the Internet, so we realized that we could reuse data on drugs and data on diseases, put those two together, and find these new uses for the drugs. Making commercial sense out of that is harder.

Dr Topol: You have already published some of your findings.

Dr Butte: We have published a couple; our most recent publication from last year was on an antidepressant that seems to melt small cell lung cancer. That is an example of how we went from actual computational data to launching a clinical trial in about 15 months. The trial cost about $50,000, not $50 million. It's certainly not a billion dollars. In some ways, the future is going to be coming up with more uses for more drugs, and getting them into patient trials in much faster and cheaper ways.

Advice for Young Investigators

Dr Topol: That's pretty striking. You are still a fairly young investigator.

Besides what you have already mentioned, do you have any other message to transmit to the younger folks out there at Medscape about how to proceed with their careers?

Dr Butte: One thing I learned being in Silicon Valley for the past 10 years is that it's no longer right to be cautious in setting an academic lab up now. In some ways, starting a brand-new academic lab is like getting funded for a start-up company. If you are not going to change the world in 3 years, neither are you going to convince investors on Sand Hill Road, or those at the study section in Bethesda, Maryland. There is a lot of synergy in those roles.

Today's role for an innovator is to convince a room full of people to give you money to execute your ideas. When you get that money, you have to change the world in 3 years.

The investigator of the future is going to have think about very high-significance projects. Shoot for changing the world. Leave conservatism behind. That would be my advice.

Dr Topol: That's pretty strong stuff. I have heard that comparison between Silicon Valley and the NIH, and how to appeal to both.

Dr Butte: My wife taught me this about 10 years ago.

Dr Topol: Thank you so much for joining on us on Medscape One-on-One. You certainly are one of the most interesting people in the world of medicine, and I wish you the best of success in your new program at UCSF.

Dr Butte: Thank you very much. Thanks for having me here.


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