Keith Lanier Black, M.D.
Head of the Comprehensive Brain Tumor Program at Cedars-Sinai Medical Center in Los Angeles.

(Interview at work with BreakThrough reporter Tom Gasparoli in Los Angeles, week of August 25, 1997)

BREAKTHROUGH: You've got three areas of primary interest as far as research goes, correct?

DR. BLACK: Of all the areas, the effort to really develop a tumor vaccine is extremely exciting. Given where we are now with our understanding of the immune system, and the information that we have on how tumor cells suppress the body's immune system to make themselves invisible to the killer immune cells, we have a tremendous amount of information into how this whole process works. We also have an incredible ability to manipulate the system biologically using strategies such as gene therapy and gene engineering to really impact on this system. We're just beginning to test these possibilities. We haven't yet begun to really scratch the surface. I think some of the early steps that we've taken with trying to develop a TGF [Transforming Growth Factor] beta vaccine really just places us at this point in first grade, and we have a tremendous way to go in really testing the paradigm as to whether or not we can really get a strong enough immune response to try to not only control brain tumors, but other types of cancer. I think this is an area that we will begin to just expand in a very dramatic way over the next five years and really test the hypothesis as to whether or not this is something that can make a big impact into our ability to control cancer.

BREAKTHROUGH: What is the hypothesis?

DR. BLACK: The concept that yes, in some select cases if you can enhance the immune response, the immune response can cause regression of cancer. The problem is that we never really understood the process until very recently. A lot of the early efforts by surgeons in the 1890's to infect their patients with bacteria to boost an immune response to cancer were really just a shot in the dark. You got a very non-specific immune response without a specific immune response to specifically attack a specific antigen or protein on a tumor cell. Our knowledge has literally exploded since then. We now know that this system called the immune system is extremely complex. We now understand this complexity a lot better. We now know the difference between a non-specific response and a specific response directed at a particular signal on a cancer cell and we're now beginning to develop methodologies to elicit a specific response on the tumors. For example, the strategy with the TGF beta has identified a particular cytokine which we can attack which we think the tumor is using to make itself invisible or cloak itself to the immune response. This is really a tremendous step forward versus what was done in the 70's and early 80's.

BREAKTHROUGH: How would you attack that?

DR. BLACK: We now understand that one of the things that tumor cells, brain tumor cells in particular, can do is release a protein into the tumor environment. This particular protein that we're interested in is called transforming growth factor beta, TGF beta. The tumor makes this protein, puts it into the environment and essentially turns off the ability of killer immune cells to recognize the tumor and mount an immune response to the tumor. Because of the rapid advances that we've had now and our ability to manipulate biological systems, we now have the ability to take tumor cells out of the patient at the time of surgery, bring those tumor cells into the laboratory and culture them in laboratory. We can genetically engineer the culture cells to now make them unable to release this TGF beta. Essentially uncloaking the tumor cells. Now, taking those genetically modified tumor cells that have been uncloaked and reinjecting them back into the patient as a vaccine under the skin, we believe we can mount an immune response that is specific against that particular tumor. When we do this in laboratory studies, we get almost complete regression of tumors in experimental models. So it's a very promising frontier. Now the TGF beta, we believe, is just one of the many possible modifications in the system. And even though the TGF beta is promising, I think that in the future you're going to see a variety of combinations bringing in different sorts of other pathways into the immune system that may allow us to have a very effective vaccine against not only brain tumors, but also breast cancer, lung cancer, prostate cancer. Other researchers are beginning to attack this, looking at breast, looking at prostate, and some of the strategies that they're beginning to develop we also think will apply to tumors within the nervous system as well.

BREAKTHROUGH: You are doing lab research right now?

DR. BLACK: We're moving into clinical studies with the TGF beta. But the strategy in our laboratory is to intensively research other possibilities that can enhance the TGF beta paradigm and that is what our laboratory effort is about. So even though we've now moved into a phase I clinical study with the TGF beta, we're beginning to think about other strategies to build on that in the laboratory to make the TGF beta vaccine even stronger in other sorts of specialized white blood cells called dendritic cells or antigen-presenting cells. Add in other cytokines, add in other types of strategies to unblock certain other defects that the immune system may have, and we believe that this may lead to very exciting possibilities to enhance the immune response to cancer. In a very focused specific way over the next five to six years.

BREAKTHROUGH: Sounds like you wouldn't mind making your brain surgery expertise obsolete. I mean you wouldn't mind not doing another brain surgery.

DR. BLACK: Yeah, I think that's clearly the goal. Brain surgery has advanced tremendously. It's a very young specialty. In the United States, it really started in the early 1900's with people like Harvey Cushing, when there was a 70% mortality associated with some of those early brain operations. Which meant that if you had to have a brain operation most of the patients would actually die just from the operation. Today, we can do a major brain resection of a large tumor in a patient and have the patient walk out and look nearly normal two days after his operation. So we've made tremendous advances. I think the ability to bring computer technology, image guided technology into the operating theater has made our ability as surgeons much better than we could have ever dreamed of. Even 15 years ago when I started my neurosurgical residency. I really view what we do as neurosurgery as trying to be, in a way, good thieves. I mean we have to devise a strategy for surgery where we can go into the brain almost like a thief, steal the brain tumor or the vascular malformation out of the brain without the person, the patient or the brain ever realizing that we've been there. That's the key to doing successful brain surgery. We have to identify the areas of eloquent brains where the language areas, motor areas, visual areas are located, find a safe door to traverse through the brain to get to the tumor without ever disturbing or manipulating those areas. I think one of the things that we are very excited about in the future is developing technology so that we don't even have to operate. One of the strategies that I'm getting to work on is the device called the Med Array, which is a device that is able to focus microwave energy very precisely with MRI guidance, image guidance that we believe may actually destroy a brain tumor or malformation in the brain without having the patient ever having to have an incision. The goal is actually to make the surgery entirely non-invasive. To have the patient have the ability to have their tumor destroyed while they are getting their MRI scan. We believe that we can very safely and precisely focus the microwave energy to completely destroy the tumor. Since the brain has no sensation the patient would never feel the tumor being destroyed, so they could essentially have the tumor destroyed in the scanner with the patient awake and essentially walk out of the scanner almost instantly having their tumor treated.

BREAKTHROUGH: Sometimes I feel like this is a one-on-one game between Dr. Keith Black and a brain tumor and you're going to fight to the finish.

DR. BLACK: I consider it a privilege, really, taking care of patients with brain tumors. You begin to realize how devastating this disease is, and we've been able to make a very positive impact for a lot of our patients, but that impact isn't as positive always as we would like for it to be. We don't always win and I've promised a number of my patients that we would find a cure to brain tumors. And one of the things that I would like to definitely see done in my career is to develop a strategy to convert this tumor if not at least into a chronic disease like diabetes that patients can just live with a normal function in life, then to actually try to cure it.

BREAKTHROUGH: It's almost like you take it personally and I don't how you couldn't when you spend so much time with it. People who like their jobs do take it a little personally. I mean personal passion.

DR. BLACK: Yes, it's a personal passion and a commitment to the patients that I've treated. My patients are actually some of the bravest people that I know. You know, these are the people that are the real heroes, who teach us the most about life. You know, when someone who is perfectly normal is certainly told they have a malignant brain tumor and they will only survive only one or two years, there's a completely different orientation to what is important in life and what life means and most of those people are the most courageous people that I've ever witnessed. And I think that I can at least try to do my part to try to find a way to better treat these tumors and try to contain them.

BREAKTHROUGH: Without going into great detail, give me an idea what the blood-brain barrier is about, because it is a very significant step you've made in the last few years.

DR. BLACK: The bradykinin opening of the blood-brain barrier is an important part, but it's limited because it's really a delivery technique. It's a way of delivering drugs or anti-tumor compounds to tumors. And so even though we have the gun to fire the bullet directly into the tumor, we don't yet have the magic bullet, so the blood brain barrier work is limited by the therapies that we have to actually deliver into the tumor. So even though we've opened the gates and we can get the therapies into the tumor, we have to find an effective therapy actually to deliver to these malignant areas.

BREAKTHROUGH: I mean you are juggling a lot of balls. You're not working alone are you?

DR. BLACK: Absolutely not. I think the reason that I came to Cedars Sinai is because the institution shares a vision to really build a world class institute to really focus on these problems and in order to do that you need resources . And they committed significant resources to allow me to bring what I feel are the best and brightest talent in one area to focus on this problem. I think once we build that kind of synergy, we've recruited the best scientists from Stanford, Mass. General, Harvard, Johns Hopkins, Mayo Clinic, already within a very short period back to the institute, and I think having that sort of focus and talent in one place will allow us to make the sort of advances that we hope to be able to do. The way that I look at it is like the Manhattan project. I think when we as a nation, as a collective group of people, decided that this is an area that we really want to focus on and tackle and you put those resources into those areas, you can make tremendous progress and strides.

BREAKTHROUGH: Who do you admire or have you admired in science?

DR. BLACK: Well, I think really the ancient Egyptians were probably one of the most impressive groups of discoverers ever. Three thousand years B.C. the Egyptians had already recognized that the brain actually controlled movement and that the left side of the brain controlled movement on the right side and that language was located on the left side of the brain. All of this information, you know, had been recorded by Egyptian physicians and stored in the library of Alexander. And it was really sort of the birth, I think, of as medicine as we know it today, because the Greek physicians that actually really began to establish the current foundation of modern medicine went to the library of Alexander, where the information had been provided by the Egyptians. That really set the whole foundation.

BREAKTHROUGH: Any particular person today, research, any location that inspires you?

DR. BLACK: No, I think it's really more of a collective body. I think this is an extremely exciting time in science. I think that we have possibilities that we never had before. I think as a society we're not recognizing what the potential is. The entire budget for the National Cancer Institute is only 2.4 billion dollars. Our government spends equal that on one B1 Bomber. When our government decides that we're going to build six additional B1 bombers that the president has not even requested, I'm somewhat disappointed in our government because we could double, or even triple our investment in cancer research making an impact into these diseases by just changing some of our priorities.

BREAKTHROUGH: And you're still disturbed enough to try and have a voice in that at the NIH and elsewhere?

DR. BLACK: I've testified in front of the Senate. I try to increase funding for cancer research. It doesn't take much. If our government decided to build one less B1 bomber, we could double our national investment into cancer research.

BREAKTHROUGH: When you think of the strides you've made already, a 100% increase would be extraordinary.

DR. BLACK: It would be extraordinary. I mean the advances will be made, but a half a million people die of cancer every year in this country. If we increase the timetable for finding cures to this disease by two years - if it would normally take us seven years, if we could bring that down to five years - you've saved a million lives. You know, this is really a tremendous opportunity, and I think given where we are now, and our understanding of science and biology, our ability to manipulate biological systems, the opportunity is there.

BREAKTHROUGH: Any message to young people, about careers, the excitement of science and math and astronomy and all of that?

DR. BLACK: I think the most important message that I could deliver is to tell people to find something that they are passionate about, that they love. For Michael Jordan it happens to be basketball. For me it happens to be science. But it makes a tremendous difference in what you do. I mean even though I may work very hard, for me it's not work. When I get up every day and come here, it's coming someplace to play. And if they didn't pay me, I would want to do the same thing, and when you have that sort of privilege, that sort of luxury, that's probably one of the most important gifts that life could give you.

BREAKTHROUGH: Where would Dr. Keith Black like to be in ten years or twenty years professionally?

DR.BLACK: If I could pick a place to be in twenty years, I would like to be able to look back and say that we've cured brain tumors and I would love to be on to something that's entirely different. Entirely new. Seek out a new challenge to discover and to explore.

BREAKTHROUGH: Why did you climb Mt. Kilimanjaro?

DR.BLACK: I climbed it because I think that, at least for me, it's important to experience life, to really have an ability to sort of sense everything that life has out there to provide. It's the same reason that I scuba dive. It's same reason that I learned to fly planes. It's the same reason I went sky diving. I wanted to experience those things to incorporate those experiences into what I am. Just like you learn about the body, try to understand yourself.

BREAKTHROUGH: What was it like up there?

DR.BLACK: It was really quite an amazing experience. I mean being on the highest point in Africa. We got there at 5:30 in the morning before the sunrise, and looking down at the cloud layer at 10,000 feet below, you watch the sun come up from the highest point in Africa below the clouds. It was a very exciting experience for me.

BREAKTHROUGH: So on the issue of parenting, since you have two kids, I'm just wondering if that's a constant tradeoff for you. You have to figure out where that line is all the time.

DR.BLACK: Yes, it's a difficult line. I guess in an ideal situation I would like to be home earlier, spend more time with them. We have three nights during the week where we get home and you know, we're going to come home and have dinner at a set time and if I need to go back, I can go back. The key is really getting it all organized so that you get a balance. You can spend time with them in the evening, find out how the day was at school and particularly try to lock off the weekends for the family and spend time with them. Solid blocks where they can just relax. This weekend, for example, we just drove down to Sea World. Spent the day at Sea World or we'll go out to the boat or we'll just go bike riding. Just do something enjoyable, whatever they like.

BREAKTHROUGH: How did your relationship with your wife start? And she, of course, is a doctor as well, Dr. Carol Bennett. A surgeon and urologist at UCLA.

DR.BLACK: When I was a medical student, I would spend essentially all night in the research laboratory doing experiments. I would go to school in the day, and from 11:00 p.m. at night to maybe 3:00 or 4:00 in the morning I would spend in the research lab. Carol would come down a lot of nights and join me. Bring me food. So she was also in medicine, could help me with some of the experiments, so you know, she has been a good supporter.

BREAKTHROUGH: How would you describe the importance of somebody like Carol, aside from the fact that you love her and have family with her, but kind of the encouragement, patience, whatever it is that she offers and how important is it to have someone like her in your life?

DR.BLACK: What I admire most about her is her ability to really just be an incredible mother. To really provide a loving, creative, compassionate, but academically stimulating environment for our kids. I think she is an incredible mom and I think there is a balance in all things, and some of the things that I've had to sacrifice and not spending as much time with the kids, she certainly has more than made up for. That's been a real tremendous asset to me, and to know that she's there, and it's something that I appreciate an incredible amount.

BREAKTHROUGH: And she's bright enough to keep you stimulated. Do you all talk about work?

DR.BLACK: We almost never talk about work. It's rare that I will come home and say listen, I've done this incredible operation or this great procedure, and she doesn't tell me about her cases. Once we leave and come home, the work stays behind.

BREAKTHROUGH: It seems like it has to because you are already consumed with it to some extent. Your life seems to be happy outside of work. How do you define success?

DR.BLACK: I certainly don't think success is the material things that you surround yourself with. I think in one's own life, the most important aspect of life is the ability to grow, to learn and to be creative. And I think one of the most important aspects for me is to make sure that my kids are also able to be creative, and happy and successful, not in a material way, but successful in sort of finding their own sort of equilibrium in life. Being able to find something that they absolutely enjoy doing and can be very stimulated by and successful in pursuing.

BREAKTHROUGH: So you are creating the same opportunities for them.

DR.BLACK: I would hope so.

BREAKTHROUGH: A way to think?

DR.BLACK: A way to think, a way to learn, a way to approach life. There's a story that I always tell about two soldiers in the trenches, an old soldier and a young soldier and the young soldier turns to the old soldier and says "Why are you doing this?" And he says, "I'm doing this so that my son can be an engineer and so that his son can be an artist." And I think that the ultimate sort of success in life is the ability to reach the point where you are an artist. Where you have the ability to just focus on the creative aspect of what you are doing rather than being in a position where you have to get up and go to work every day to sort of produce and to survive. And whether they are creative and artistic in music, or science, or whatever endeavor that they decide to pursue, I hope that my kids can be artists.

BREAKTHROUGH: You mean an artist in terms of what you produce or an artist in being a creative thinker, a problem solver?

DR.BLACK: An artist in terms of being creative. Art and science, I think, are very interchangeable, because the best scientists are actually the most creative scientists. Art is a discipline that is practiced with passion and science is a passion that is practiced with discipline. You know, the ability to do science is really the ability to create, to make something that doesn't exist. To explore and develop things that people haven't thought of before or haven't developed. That's the most exciting aspect of it.

BREAKTHROUGH: It really is, and I guess part of art also is leaving a legacy. I mean leaving a legacy on a daily basis, a weekly basis, and leaving a legacy in your career. Good art leaves a legacy. You seem to be a man who wants to leave a legacy of discovery, of new methods, and the people behind you. Is that important to you?

DR.BLACK: I think it's important for me to personally know that I've contributed something positive to society, something positive to the world. I would like to leave knowing that I made it a little better than it was when I arrived. It's not that important to me to be recognized for doing that. I don't care if there's a statue or plaque that says "in memory of Keith Black," that's not essential. But I think what would be most important to me is to just know in my own heart that yes, I've made a difference, in that I am leaving it a little better than it was when I arrived.

BREAKTHROUGH: I'm sure that you must feel, especially with some of the advances you've made already, you and your team, that there's never a time when you want to just say, "Well, okay I'll take a year or two off." Because medicine can change so fast, and how many people are going to get brain tumors in that period that you take time off?

DR.BLACK: Right. I'm not sure that I would necessarily want to be doing exactly the same thing I'm doing now, 20 years from now. My dream would be to find a cure for malignant brain tumors. And if I did that I would like to go on to something else, something entirely different. There are a lot of things that the world has to offer in terms of exploring new adventures and entire new bodies of knowledge. I was just telling Carol the other day I would love to go back and take a class in astronomy, for example. That would be fantastic for me to be able to do that, or to go back and take a class in marine biology, but the ability to continue to stimulate yourself academically, to always be challenged is what I find most enjoyable.

BREAKTHROUGH: Who do you look up to in life?

DR.BLACK: I think the person that I probably look up to most is my father. I think of all the people I've met in life, he's the person I admire that most. I think he's probably the most incredible father in the world, even though I never tell him that. He absolutely spent his entire life devoted to making sure my brother and I had the best opportunity that we had to sort of develop into the best that we can be. He's the ultimate educator. I would describe him as the ultimate educator and the ultimate teacher.

BREAKTHROUGH: And you can remember those times, dissecting the frog and whatever it was when you were six and eight and ten years old? You can remember those like it was yesterday?

DR.BLACK: Yeah, and with my father it wasn't so much that he would necessarily sit down and dissect the frog with me, but what he would do is if he saw me dissecting a frog heart, he would go and get a chicken heart, which was a little larger, so that I could see the different chambers, and he would just provide me with the opportunity to sort of explore and learn about the chicken heart. It's almost an independent learning process. And after I had moved through that, he would go and get a cow heart so that I would look at the valves of the cow heart. My involvement growing up was incredible. It was like having a mentor of great stature with you every step of the way. I just hope I can be half the father that my father was.

BREAKTHROUGH: You're not going to shortchange your mom, are you?

DR.BLACK: No, my mother was incredible as well. I mean, she was right there with him.

BREAKTHROUGH: So most of us were throwing rocks at cars and you were dissecting hearts? Did you ever do anything wrong in your life?

DR.BLACK: Oh, absolutely. I blew up the kitchen with a chemistry set. And amazingly, my mother didn't get upset So, yeah, I definitely did some things that were not too great.

BREAKTHROUGH: But you have tremendous self discipline. What stood out for me as I watched you today and yesterday, is focus, drawing everything that you had....15-20 years of medicine right there tapping into it. But you're calm. You're focused. I don't know where you get that. Is that one of your strengths as far as you're concerned?

DR.BLACK: I think that I take it for granted. I would hate to see a neurosurgeon who's not calm.

BREAKTHROUGH: So would the patient! What makes you so calm? Is that something you were born with?

DR.BLACK: I never noticed a change. I never noticed that my personality changed over time. So I would assume that it was a trait that I always had.

BREAKTHROUGH: Is your father like that?

DR.BLACK: No.

BREAKTHROUGH: There's the secret...your rebellious streak?

DR.BLACK: Absolutely.

BREAKTHROUGH: Thank you, Dr. Black.

DR.BLACK: You're welcome.

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