Jilliene Mitchell: Hello, I’m Jilliene Mitchell. I’m talking today with Dr. Kevin Tracey, director of the Feinstein Institute for Medical Research and president of the North Shore-LIJ Graduate School of Molecular Medicine. Later this afternoon, Dr. Tracey will be giving the DeWitt Stetten, Jr. Lecture at NIH. He will discuss the surprising connection he’s discovered between the nervous system and the immune system. The National Institute of General Medical Sciences has funded Dr. Tracey’s research since 1999. Welcome Dr. Tracey.

Dr. Kevin Tracey: Good morning.

Jilliene Mitchell: Can you explain what your research has revealed and what it might mean for patient care?

Dr. Kevin Tracey: Yes, my research reveals that the brain, through nervous connections, through neural connections, can actually control the immune system in real time.

Jilliene Mitchell: You were a practicing neurosurgeon for many years before you decided to focus on basic research. How does your medical background inform your current work?

Dr. Kevin Tracey: We had a privilege of caring for patients for many years. And in that time you see people at the best times of their life and at the worst times of their life. And you really realize that in some cases medicine and the practice of medicine, and in my case neurosurgery, can improve the quality of life. But at other times the practice of medicine or practice of surgery runs up against an inadequate knowledge base. And that can provide, on the doctor side, on the practitioner side, some of the most frustrating and difficult experiences as you have to talk to family and talk to patients about the fact that we don’t understand what to do next. We don’t really understand exactly what’s going on. And I think for me, it was dealing with situations like that and memorable patients like that that really caused me to begin to think about the fact that only by building a research foundation, a basic understanding of how diseases are caused and how diseases can be treated with new ways. For me, that was the only solution for this frustration of not being able to understand what was going on in some patients. So the practice of neurosurgery was a wonderful privilege. I did it for many, many years. I trained in neurosurgery at New York Hospital in Cornell for 10 years and I practiced at North Shore University Hospital; I practiced neurosurgery for 10 years. But during that time much of my focus and many of the questions that I spent a lot of time thinking about in caring for patients was what are the underlying problems in these diseases and how is it that if we studied them or looked at them in a different way how could we change treatments. And so now from that sort of experience has really come, in a roundabout way, a connection back to my basic roots, which is to look at how does the brain and the nervous system interact with the body, in this case the immune system, to control the production of factors that cause disease. And so really in a surprising twist … we didn’t set out to do this 20 years ago or 25 years ago, but in a surprising twist, the two things I’m most interested in turn out to be fundamentally connected. So now looking at it from a higher point of view, it’s possible to understand how to control this system. So looking at the possibility of implanting a pacemaker on the Vegas Nerve, for instance, to control the output of the immune system, and it’s the output of the immune that causes the disease. And so really, being a neurosurgeon made me a better scientist, and I think being a scientist made me a better neurosurgeon.

Jilliene Mitchell: What parts of your work do you find especially satisfying?

Dr. Kevin Tracey: The idea that something we think of or discover or create will be used to reduced the suffering of some patient, someday. And the parts that I find most exciting are those that to me seem to be very close to actually happening in the clinic. We can really talk in real time about the possibility that some of the discoveries that I’ll talk about this afternoon may be translated into either drugs or devices that will reduce human suffering. I had the privilege of working with groups of people over many years in some of the early days of cytokine biology and now we get to enjoy discussions with patients who received drugs that target cytokines, such as anti-tnf or anti-IL1, and these patients will tell you that these drugs have changed their lives. And so I hope every day going to work that something that my colleagues and I are going to do today or tomorrow will actually be translated into a drug that will improve the quality of someone’s life.

Jilliene Mitchell: You’ve written a book called Fatal Sequence about the hospital course of a former patient, a baby girl with severe sepsis, and you connected her case to subsequent scientific discoveries about septic shock. What motivated you to write a book for a general readership?

Dr. Kevin Tracey: I was motivated to get the word out because I found myself haunted by memories of this child. Janice was 11 months old and she was crawling across the kitchen floor when her grandmother was cooking spaghetti. And she crawled under her grandmother’s legs and caused the woman to spill the boiling water onto this baby, which of course burned her severely over almost three-quarters of her body. And she was my patient. And she came to the New York Hospital and we admitted her to the burn unit. And she did fine for the first day or so but then she suddenly had a complication of septic shock. And this was an extraordinarily dangerous problem for her. Her blood pressure plummeted and it was a medical emergency. Fortunately, she survived that experience but I’ll never forget talking to the family and the family asking very simple questions like “What caused this?” And “I don’t know” was the answer, “maybe bacteria.” And they said, “Well, did you find any bacteria?” And we said, “Well actually, no, we didn’t find any bacteria.” “Well then what could have caused it?” And we said, “Well, toxins could have caused it.” And they said, “What kind of toxins?” And we said, “Well, maybe there were toxins from bacteria.” And the family said “But you just told us you didn’t find any bacteria.” So the frustration of talking to anguished parents over a severely critically ill child really burns a memory in your brain. And going forward, we now do have a very good understanding of what happened to Janice. We know the identity of the molecules that cause septic shock. We know that TNF can cause acute septic shock. And we know that other molecules can cause other complications of critical illness. We know that HMGB1 can cause a complication called severe sepsis. And we’re really coming to ask the next question down the road, which is how is the production of these potentially dangerous molecules, how are they controlled. And the answer is they seem to be controlled in part by the brain and by the nervous system. And so there has been a steady progression of our knowledge base which ever since the day we took care of Janice, and we just hope that this growth of this knowledge base will circle back to drugs that would help patients like Janice. Janice survived for a month. And the amazing thing about her case was that we were getting ready to send her home after her first birthday party. She was getting a bottle from a nurse and she rolled her eyes back and died. And it was a devastating personal experience for me. The cardiac arrest was something that I’ve dreamed about for many, many years, and she shouldn’t have died. The reality is that we’ve figured out what causes shock. We’ve figured out what causes severe sepsis but to this day I don’t know what Janice died of. And so perhaps that’s why I wrote the book. Perhaps it was just the time to stop and really try to integrate where we are in this progression of knowledge. But hopefully as in any sort of writing experience or speaking experience, the preparation for the writing and the preparation for the speaking can hopefully contribute to a future advance, and that’s what I hope from this book.

Jilliene Mitchell: What are some of your interests outside of the lab?

Dr. Kevin Tracey: I have a wonderful wife, Tricia, and four daughters and I try to spend as much time with them as possible. I love coaching their soccer team and I love playing with them on weekends and this is perhaps the most inspirational part of my life, which is the family life.

Jilliene Mitchell: Thank you, Dr. Tracey.

Dr. Kevin Tracey: Thank you.