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Michael Yaffe

Michael Yaffe
CREDIT: Larissa Sasgen

This week, Science is running an interview with systems biologist and trauma surgeon Michael Yaffe, who treated victims of the Boston Marathon bombings. At Science Careers, we're presenting an extended version of that interview, with extra information on his connections to the bombing and his very unique career path. This interview has been edited for clarity and brevity.

It's not often that a systems biologist is also a trauma surgeon, active in the Army Reserve—and even rarer still that he treats the victims of a historic bombing. On 15 April, Michael B. Yaffe, who holds positions at the Massachusetts Institute of Technology (MIT) in Cambridge and Beth Israel Deaconess Medical Center in Boston, was rehabilitating a broken leg when two bombs exploded near the finish line of the Boston Marathon. Yaffe rushed to the medical center and was soon helping to treat victims. During the last day of the hunt for one of the bombers, he was locked down in the hospital; after injuries, both bombing suspects ended up there. (One died.) In an interview last week, Yaffe noted how injuries to humans parallel insults to cells, and he described the emotions of the "surreal" week, in which an MIT police officer was also killed, outside Yaffe's research lab, by the alleged bombers. "I have had a couple of bad dreams. But overall, I think I am doing pretty well with this. Let's see what happens over time," says Yaffe, who is chief scientific editor of Science Signaling (published by AAAS, which also publishes Science and Science Careers). His remarks have been edited for brevity and clarity.

We see a significant number of laboratories, at least in the Boston area, that are now empty space because people who were trying to bridge the gap between the clinical world and the basic science world have encountered the clinical department saying, "with funding so tight, you would probably be better off spending your time just seeing patients."

Q: Can you talk about your experiences in the aftermath of the bombings?

M.Y.: I was in the gym. I saw on the television that there had been a bombing. I knew that my partner Carl Hauser was on for trauma at Beth Israel, so I sent him a text message. And it goes to show you how much I under-estimated things, I said, "I doubt that it is a mass casualty. But just in case, let me know if you want me to come in." Two minutes later, he sent me a text message that said, "Come on in." They already had half a dozen people or so from the bombing in the emergency room. Everybody came together and worked in a way that I have never seen before. It functioned like a well-oiled machine.

Q: What was your role?

M.Y.: It was mostly as a surgical intensivist and a trauma surgeon. So most of what we did was stabilize patients. Because the wounds were mostly lower extremity, it was really the orthopedic surgeons and plastic surgeons and vascular surgeons that did most of the operating. There were a total of 25 patients. I have to be careful that I don't violate HIPAA [patient privacy] rules. A number of them had traumatic amputations. Extremities missing. Many of them had combinations of injuries: broken bones, soft tissue injuries with significant tissue loss. Some burns. A lot of … it was pretty horrendous.

Q: Did your Army Reserve background play a role?

M.Y.: There were a number of lessons that had been learned by the military in Iraq and Afghanistan that I think had a direct impact on the number of patients who survived this disaster. One was the early use of tourniquets. The other was rapid evacuation without necessarily trying to stabilize people. A number of the hospital personnel and I wrote peoples' injuries in indelible marker on their chests so that if the chart got separated from the patient, we could figure out which patient is which.

Q: After the first shootout, the hospital was in lockdown. What was that like?

M.Y.: It was surreal. I think we would have felt worse if we had been trapped at home and unable to get to the hospital. But it was an odd feeling to know that you could not leave.

Q: Is there some way that your scientific background played a role in your experience or management of events?

M.Y.: My particular area of science is systems biology, which means you have to think in an integrative manner. When you take care of polytrauma patients, you also have to think very integratively, because it is not just a broken bone or a laceration. You have to think about more than the musculoskeletal system; you have to think about all the interactions between [body] systems. And you have to coordinate care among many different specialties, orthopedic, plastic surgery, vascular surgery, trauma surgery, pain management, infectious disease, social work, and psychiatry. So I think that sort of taking an integrative approach to biology lends itself naturally to taking an integrative approach to care.

The other part is that, as a PI [principal investigator], you have to learn how to manage a lab of people effectively because you have a goal and you have all these different assets. And you have to be able to use your assets most effectively to reach your scientific goal.

Q: How does the scientific amalgamation that has been your career translate to medicine?

M.Y.: Critical care medicine really is applied signal transduction. Sometimes you look at a patient and you say, "Well this is just a classic case of too much IL-1," or "Wow, this is really what happens when you have a cytokine storm." You can think through the physiology in molecular terms.

Also, we treat our patients in the intensive care unit, for example, by administering drugs that affect adrenergic receptors. It is all clinical pharmacology, which is really applied signal transduction.

Q: How do you deal with the fact that the suspects were at the hospital where you work?

M.Y.: I can't say whether I was involved in their care or not. But what I will say is that I think the attitude of most of us at the medical center is that we are here to take care of people. Same thing like in the Army. We take care of our soldiers and we take care of insurgents. Our role is to heal the wounded. We're not judges. That is a different part of our society.

Q: As a trauma surgeon, you see severe injuries often. Was there something different about this situation?

M.Y.: I was trained to do this. That helped a little bit. And when you are privileged to be able to take care of the victims, I think that is actually very therapeutic.

Also, we were so lucky that this happened in Boston because we have five level one trauma centers within about 10 miles of where the bombing occurred. The EMS folks did an amazing job of triaging the patients so that no one trauma center got clobbered with 100 patients.  And because it was a holiday, the operating rooms weren't filled with elective cases. And because it was a pseudo-holiday, there were still a lot of staff around. And because it happened at three in the afternoon, that is when nurses change shift, so you had twice the number of nurses that you would normally have. It was just fortuitous that it happened on a day that was most opportune for being able to take care of a disaster like this.

Q: What happened after the subsequent shootouts that involved death of MIT Officer Sean Collier?

M.Y.: I felt like I had a particularly tight connection to those events. It is public knowledge that both of the bombers came to the Beth Israel Deaconess Medical Center for treatment. The officer was shot outside my building at MIT, although thank God it wasn't on campus. So, taking care of the victims has sort of emotionally tied me very closely to this event. I have had a couple of bad dreams. But overall, I think I am doing pretty well with this. Let's see what happens over time.

Q: Now maybe a chapter is closing on the bombings because they've transferred the remaining suspect to a detention facility. What are your thoughts?

M.Y.: I had the experience, I think many of us did, of coming home after they let us go from being locked down. We hugged our children in a different way than I might have hugged them before. I thought about some of these poor victims and realized how fragile we are. You hug your children and you cry. I think there was a certain innocence those of us in Boston have lost as a consequence of this.

Q: How did you begin your journey, as a scientist, a clinician or both?

M.Y.: It was a little bit of both. I have a very strange background. Maybe insane would be a better word. My undergraduate degree was in materials science and engineering.  And I was always interested in surgery and clinical medicine. I kept going back and forth. I'd work 36 or 40 hours in the clinic, and then I'd spend 8 to 12 hours in the lab. I guess I am an adrenaline junkie. That accounts for why I find science and trauma surgery so exciting: They are both a good way to get your fix.

The other thing of great help to me was, before we had children, for whatever reason I didn't need a lot of sleep. I actually don't like to sleep. I view it as a waste of time. For a lot of my Ph.D. and residency training, I could get by on somewhere between 3 and 4-and-a-half hours of sleep a night.

Having kids made it much more difficult. Now I need 5 to 6 hours a night, which makes it hard.

Q: How many kids do you have?

M.Y.: Two. I started late. I have two kids, a 5 year old and a 10 year old. And my wife is a pediatric oncologist who does bone marrow transplantation. She also does basic immunology, part-time, and clinical work, part-time. She has been a big inspiration for showing me how to combine clinical work and basic science.

Q: What were the challenges you encountered in going from materials science to trauma surgery and signal transduction?

M.Y.: I think the biggest problem initially was making the transition from materials science and condensed matter physics to biology. When I started, biology was a very soft science. Whereas physics and engineering, you could control everything except one variable. You could write things in closed-form equations, and you could predict what would happen.

I had an absolutely fantastic undergraduate research mentor who was totally inspirational. He had a really unique ability to take things from one field and bring them to apply to another. That proved to be remarkably useful.

Then, as a graduate student, when I struggled with trying to make this transition to biology, I was lucky again because my Ph.D. mentor had been a chemical physicist who had made the switch to biology. And so, when I would get frustrated with the lack of mathematical rigor or the lack of being able to control every variable except one in biology, he had been through that. He was able to guide me in the transition from being someone focused on engineering and physics to becoming more comfortable with biological systems.

I was lucky to have three great mentors. My postdoc with Lew Cantley (at Harvard Medical School) opened my eyes to the world of signal transduction. There is an engineering element to thinking about cell circuits that is a natural place for biologists that are interested in more physical chemistry and physical approaches to find a home.

Q: Would it be fair to say that given you both a basic scientist and a surgeon, you are one of a rare breed?

M.Y.: I think that is true. There are a handful of surgeons who are also scientists. I am fortunate that some of my colleagues are actually both. I think we probably have the one department in the country where people in the surgery department actually publish in Science and Nature.

I have consistently found that the surgeons are incredible scientists because they have this ability to see things in a way that straightforward biochemists and cell biologists might not be able to see. I think there is certainly a world view that surgeons like to cut and don't think deeply, but I have found my surgical colleagues to be some of the most interested in learning the basic science and then trying to apply it.

Also, I find that the residents, the doctors in training, are really quite excited to try to bridge the basic science they learned in medical school with the clinical care of the patients.

It used to be there was something called the triple threat, which meant that you could do research and teaching and clinical care. And that model served academia in biomedicine for a long time. It has become harder and harder to sustain, in part because in order for people to be productive in bridging the interface between the clinical sciences and basic science, you have to have a foot in each camp. You have to be able to see something at the bedside and think of how you can address it in a model organism or some kind of detailed biochemistry experiment in the laboratory.

And it is hard because metrics are placed on being able to do clinical work. You have to do a certain volume of clinical activity, and you have certain scores and grades from your patients. There is certainly a need for that because you want patients to be taken care of by someone who is clinically excellent. But at the same time, it is hard to do two jobs 100 percent of the time each. I think we have to find some new model, and I don't know what it is.

Q: What would be the effects of sequestration [the across-the board U.S. government funding cuts that occurred this year] on this model? Isn't going to make it even more difficult?

M.Y.: Absolutely. I think as funding gets tighter and tighter, you'll see more and more people who are trying to bridge the interface saying, I'll either just do clinical work or give up my clinical work so that I can write three times as many grants because the funding rate is so low.

Q: Particularly the clinical institutions. Will they say, "You know, we don't have any time now for you to do research"?

M.Y.: We see that happening now. We see a significant number of laboratories, at least in the Boston area, that are now empty space because people who were trying to bridge the gap between the clinical world and the basic science world have encountered the clinical department saying, "with funding so tight, you would probably be better off spending your time just seeing patients."

Q: How does your surgical background influence the experiments that you set up in the laboratory?

M.Y.: We are focused in my laboratory on doing experiments that ultimately will be able to have impact on human disease. We don't do a lot of experiments in areas of biology that are fascinating and important to understand but relatively far removed from medicine. But we do hard-core basic science. We do a certain amount of structural biology and x-ray crystallography. We do a lot of detailed signal transduction pathway mapping, Kinase assays and binding assays. A lot of physical biochemistry. But I can link all these things in about two or three steps to human disease.

One of the reasons I wanted to work in Lew Cantley's lab and learn signal transduction was, I was struck by the fact that we could do the same operation with two different patients and one would do spectacularly well post-operatively and be home in 3 days, and the other would have one complication after another and end up in the intensive care unit for 6 months. There really wasn't anything different about the technical procedures we were doing; something fundamentally different about the signaling response to the injury that we had inflicted as surgeons was responsible for the difference in outcome. I was desperately interested in trying to understand how we could manipulate signaling pathways to improve the treatment of injuries.

Q: Is there some connection to be made between the responses of cells encountering stress or injury versus a whole person? Are there any parallels in recovery?

M.Y.: Yes, absolutely. This is an area that I think really needs to be more thoroughly addressed. We're pretty good at taking cells in isolation and being able to understand, at least in part, their response to injury. But in my mind at least, integrating many cell types within a tissue and understanding how they communicate with one another remains largely a black box. The best understood systems, in this regard, come from immunology. But, particularly in the study of sepsis and trauma, I don't think we have a very thorough understanding.

It is a vastly underfunded area. If you look at largest causes of death in America, sepsis and trauma rank right up there with cancer and heart disease. But the NIH [National Institutes of Health] resources devoted to the study of sepsis and trauma are a tiny fraction of what we spend on treating cardiovascular disease and cancer.  We don't have a constituency. There is no American Sepsis Society—no society that is trying to raise money to fund these diseases despite the fact that they rank right up there in terms of sources of mortality.

Q: Does your work in cellular responses to overwhelming infection and sepsis inform your decisions in the clinic?

M.Y.: I think they do, but not as much as I would like. With burn patients, it certainly changes the way we think about things. In complex wound management, we think a lot about what the signaling pathways are and what factors can be involved and what kind of things we could do to improve things. But we don't yet have the rational therapeutics for tissue injury that we have for things like cancer. Although there has been an effort, we have not been as successful in identifying specific molecular agents for use in sepsis and trauma. I just think it is more complicated.

This is where systems biology or systems pharmacology comes in. The idea that we should look at clinical therapeutics from a systems point of view—that is clearly a big area for future growth.

Q: Is that part of the reason that you decided to launch [the biotech company] Merrimack?

M.Y.: That is exactly why: How could we use systems biology to address the rational use of therapeutic drugs?

Q: What is going on with that company now?

M.Y.: The company is focused in large part on coming up with specific combinations of growth factor receptor inhibitors that have therapeutic efficacy in cancer. It has interests in extending that work into areas like inflammation.

Q: Financially, how were you able to launch it?

M.Y.: We were very fortunate that the CEO Bob Mulroy knew how to do this. I'd say we survived because we weren't dependent on classic venture capital. As a result, we had the freedom to operate for a long period of time, while the people in the company figured out how to make it work.  I think if we'd been funded by a traditional venture capital approach, where you have a very short window in which you have to make a profit, we would never have survived.

It was the wisdom and foresight of the investors that made this possible. I was never under intense pressure to produce something. We were really encouraged to think deeply and do it right. Mulroy and Ulrik Nielsen, the chief scientific officer, were the two people who were absolutely responsible in the early stages for making this work.

Q. If you could offer a take home message about your scientific and clinical experiences, especially in light of recent events, what would that message be?

M.Y.: When I started, and I said, "I am going to be a surgeon and do x-ray crystallography," people looked at me like I was from another planet. But now the world is opening up to this kind of thing. It is very difficult to go between the two fields. But I think if I could say two words for people that try to do this: "Never quit." Keep trying to bridge it.

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