Right Time, Right Place: SFMMS Interview with Donald Abrams, MD

SFMMS INTERVIEW

RIGHT TIME, RIGHT PLACE

Donald Abrams, MD on his career as a pioneer in AIDS care and research, integrative oncology, medical cannabis, the right to die, and more. Steve Heilig, MPH

Donald Abrams, MD finished his hematology/oncology fellowship at the University of California San Francisco just as the AIDS pandemic was exploding in San Francisco. From that challenging, even harrowing start, he went on to do landmark work on HIV itself and then on numerous other controversial medical issues. His papers have appeared in such journals as the New England Journal of Medicine and JAMA. Newly retired, he spent his whole career at “The General” and UCSF, winding up as a full professor of clinical medicine, chair of his division, and a leader in integrative oncology at the UCSF Osher Center for Integrative Medicine. A member of the SFMMS for decades, he looks back at his illustrious career here. This is from a dialogue we did for the New School at Commonweal in Marin. Interviewed by Steve Heilig, MPH.

First I’d like to hear a bit about yourself in terms of where you grew up and how you first found your way into medicine. I was born in New York, and my family moved when I was five to Cleveland. I come from a long line of no doctors. They wanted me to be a rabbi, but I wasn't going to be a rabbi. Medicine, biology interested me and was probably what I was going to do. So I left Cleveland for the first time to go to Brown University where I was initially accepted into a seven-year program that was going to lead to an MD degree. But in the middle of my training, I went to Europe for my first time, came back and said, “Gee, I don't think I want to stay in Providence, Rhode Island for the rest of my life.” So I dropped out of that program and I tried to apply to medical schools, but everybody said, “Oh, you're not going to get in any place because you don't have any grades” because Brown was very progressive and did away with grades. But I wound up getting into Stanford, so that wasn’t too bad. And how did you first get an inkling of your chosen specialty?

I really thought I was going to be a psychiatrist. But I spent time at McLean hospital, which is Harvard’s psychiatric hospital, and I was working in the borderline unit, where I was more accepted as a patient than as a medical student. Then I went off to the Maudsley Hospital, which is the psychiatric Institute in London. And I was disturbed that what we called schizophrenia, they called depression. And what we call depression, they called an adjustment reaction. I said, “We're speaking the same language, but, they say this and we say that and I think I need something that's a little bit more definitive or measurable.”

After Stanford, I did my internship and residency at Kaiser in San Francisco and I really bonded to a lot of my patients who had leukemia and cancers who were dying. I think for me, it had to do with my own fear of death that I always say was probably vibrated into me by my parents who lost three of my four grandparents from my birth to my second birthday. My mother was 22 when I was born. She lost both of her parents and I feel that this sense of fear of losing people you love was inculcated into me and I needed to get over that. So by dealing with people who were at that transition, I found a lot of gratification. I first actually wanted to be a hematologist. But I got into my hematology fellowship at UCSF, right as AIDS broke, and AIDS was cancer-Kaposi’s sarcoma and non-Hodgkin's lymphoma. So in the middle of my hematology/oncology fellowship at UCSF, I changed my course a bit and stayed an extra year so I could get my boards in oncology instead of hematology.

And you ended up staying here, in fact, and practicing and working out of San Francisco General, which really became an epicenter for care and research. Yes. The first year of my hematology/oncology fellowship, I had a young woman die of a very bizarre leukemia. Right after she died, her father, who was in the military, came and showed me his lab report, and he had an even more bizarre leukemia. I said, “Oh, this is weird. This must be viral.” So I did a lecture for the fellows on virally induced malignancy. And in the second year of your fellowship, you're supposed to work in a laboratory and I really had no interest in that. But my mentors invited Harold Varmus to my lecture on virally induced malignancies, and he of course with Mike Bishop later got the Nobel Prize for their work on retroviruses and oncogenesis. This began a conversation between Harold and myself, which ultimately led to me spending the second year of my fellowship trying to work in his retrovirology lab, right at the time that AIDS exploded. I really thought AIDS was a retrovirus, just from what I knew about retroviruses, and I tried to convince some of the 34 postdocs that were in the lab that this disease is caused by a retrovirus, and you should help me look at some of the tissues I'm bringing back from patients that I was seeing in clinic. And everybody said, “Oh, well, there's really no such thing as a human disease caused by a retrovirus, you’re wasting your time.”

Ultimately, I was really unsuccessful and frustrated in the lab. I was more interested in the syndrome of persistent swollen lymph nodes that I had perceived in gay men at Kaiser. I established a cohort, an observational study, looking at 200 gay men with swollen glands to see if they were going to go on and get the more severe manifestations of what we still weren't calling AIDS yet, but the Kaposi’s sarcoma and the pneumocystis, and that work made me think that “OK, I don't really have time to spend trying to extract DNA and RNA from lymph nodes. So I'm going to go back to the clinic” and that's what I did. That's when I moved from UCSF to San Francisco General. Paul Volberding

had become the first ever full- time oncologist at San Francisco General and he had seen his first case of Kaposi’s sarcoma, and he came to me and said, knowing that I was a gay man, "You should get involved in this." And ultimately, I got moved over to General where all the action was.

That meant a sudden and big influx of patients with still somewhat mysterious presentations. It seems maybe you were trying to confront mortality as an oncologist and then you get into HIV where, for quite a few years there, everything that was being done was not effective in terms of saving lives. Everybody was dying for quite a while.

Yes, I think I had to get over my fear of losing people I loved. I had four partners from age 25 to 39. And they all died. We had a lot of loss. In fact, Clint, my husband now for 26 years, just pointed out that my career in medicine has now been bookended by pandemics. And I find it very interesting. You know how my reaction to the first was very different from my reaction to the second. In this pandemic, my last two weeks of inpatient medicine attending on the wards at San Francisco General were scheduled to be April fourth to the 17th. And two weeks before that, I said, “You know what, I'm 70. I'm not going to do this.” Whereas in the other pandemic, I jumped in headfirst. They are really very different diseases, very Yin and Yang, as it were, but sort of interesting to me my response to HIV AIDS and my response to COVID-19 being so sort of diametrically opposed.

You're talking basically about both occupational and a more personal risk. That was a big deal in the very beginning of HIV when we didn't even know how it was transmitted, if it might be aerosolized, etc., and that was pretty much universally fatal. A lot of the people on the frontlines were truly heroic there.

Paul Volberding and I spent many a conversation after we got home from work on the telephone saying, Oh, my God, you know, what is this? One day I was working in the emergency room at Kaiser, moonlighting, and I looked at my hand, and I had these three purple spots on my palm. I freaked out, certain I had Kaposi’s sarcoma. So I called Marcus Conant, I think it was a Sunday, and he said, “Come to my office.” Marc was the premier dermatologist working with this new disease. I met him at his office. He arranged to come in and see me on Sunday, and he looked at my hand, and I thought he would reassure me but instead he took pictures of my hand. I said, “Oh my God.” He said, “If it doesn't go away in a week, then I'm going to do a biopsy.” Well, suddenly, I remembered that probably when I was carrying the canister of liquid nitrogen to collect lymph node biopsy specimens, some had splashed onto my hand. And those three purple spots were actually liquid nitrogen burns, and they went away.

You began a community consortium of physicians who were doing research on HIV and we hosted that at the Medical Society. What do you think are your most significant contributions in this regard to HIV research?

Paul was called to a meeting with Mayor Dianne Feinstein. The goal of the meeting was to make sure that San Francisco General didn't become just an AIDS hospital. Because there was a risk that every patient admitted was going to have HIV AIDS and since we are a teaching hospital, they didn’t want it to be like, if everybody had diabetes, that wouldn't be a very broad spectrum for teaching. Paul came back from that meeting and said, “You know, these are all your friends from the gay doctors’ organization. Why don't you start meeting with this group and figure out how we could make sure that we don't get overwhelmed with these patients so that we could triage some of them to their hospitals if we get too many admissions.” We called this group the County Community Consortium, eventually dropping the County because people always got confused as to what the three C’s stood for. Although we started as an educational group, we actually became the first community-based clinical trials group in the country dealing with HIV AIDS.

I suppose the Consortium was one of my contributions in that the Consortium planted a seed that then grew into a network that was funded by the American Foundation for AIDS research and, later, the NIH. That's how I became a friend of Tony Fauci because he was ultimately in charge of our network. A lot of gay men and women who went into internal medicine or family practice, thinking that the most severe thing that they would ever treat would be syphilis or gonorrhea but now were dealing with all these young men who were dying. I felt that the Community Consortium brought together people for a group therapy, if you will. We educated each other about this new disease, but we also could come together once a month at the Medical Society, and just be together and share the sadness and share the loss. The Consortium had a scientific advisory committee and an executive board. This was at the time that ACT UP was becoming popular in San Francisco. NIH wanted to fund “community based” clinical trial programs and we thought it would be a good idea then to bring these community activists into the Consortium. So we established a community advisory board that was made up of patients as well as the activist community. That was another first - Paul and I wrote that up in the Hastings review of medical ethics because it was a new concept to establish a board that included people dealing with the disease, and that's become popular for other conditions as well now too.

We conducted a lot of clinical trials in prevention of opportunistic infections. We did an inhaled pentamidine trial that was one of the first to try to prevent that infection. We tried to prophylax all the infections. I also defined that subset of patients with persistent generalized lymphadenopathy and described them as being a group at risk to develop the more severe manifestations of HIV AIDS. I also was one of the people who contributed specimens to Robert Gallo’s lab at the National Cancer Institute that he used to first describe HTLV-3, or the AIDS retrovirus, back in 1985. I just retired and left my office at Zuckerberg San Francisco General that I've been in for 37 years, and it required packing a lot of boxes which I donated to the university library archivists. But I would look at this stuff that I did in the 80s. And I said, “Wow, I didn't remember that,” and I was pretty impressed.

You were being published in journals like the New England Journal of Medicine and so forth, and on very important topics. And one was medical use of marijuana. How did that come about?

In 1992 “Brownie Mary” Rathbun had gotten arrested baking cannabis brownies for AIDS patients at Zuckerberg San Francisco General. A letter was sent to the AIDS Program suggesting continued on page 26

that a clinical trial showing the benefit of cannabis should come from Brownie Mary’s “institution,” as if she was our Dean. I said, Okay, I went to college in the 60s and I fought the government to conduct a trial and ultimately succeeded. That began my interest in plants as medicine which ultimately took me to the Telluride Mushroom Festival in Telluride, Colorado a month after I'd done my first ever jury duty, and came home and said, I want to go to law school. But in Telluride, I met Dr. Andrew Weil, who described a two year online distance learning fellowship you could do with his program in Integrative Medicine at the University of Arizona and I said, “I don't want to go to law school, I want to do that.” So I did and when I finished that fellowship, I changed my career direction from HIV AIDS to integrative oncology. How do you define “integrative” here?

I say integrative oncology is the evidence informed combination of complementary therapies with conventional therapy to benefit the whole person, mind, body and spirit living with cancer. It is patient centered and relationship based medicine. When I was pursuing my fellowship, I would be reading about nutrition for the first time because we didn't really learn about nutrition at Stanford Medical School when I was there. This has become my passion now - nutrition and cancer. I tell patients that I see at the Osher center that cancer is like a weed and other people are taking care of their weed because I'm not their primary oncologist. I say it's my job to work with the garden, and to make your soil as inhospitable as possible to growth and spread of weed. And I do that by looking to see how you fertilize the garden. That is, what you eat and what supplements you take. Supplements are also an area of my interest. But physical activity and weight control are also very important. We know that physical activity decreases the risk of a number of malignancies and patients with various cancers who are physically active fare better than those who aren't.

Another big focus is on stress. I see a lot of people when I ask “Tell me your story” who weave a story as if stress caused their cancer. I don't think stress in and of itself causes cancer, but stress which is epinephrine which is lymphocytotoxic and cortisol which is an immunosuppressant. So decreasing stress is important. In the old days (pre-pandemic), when people could be physically close to each other, massage was a good thing to do. Reiki, all of those energy medicine interventions. I like yoga for a stressreducing physical activity. I'm also a huge proponent of traditional Chinese medicine. Traditional Chinese Medicine is all about expelling evil and supporting good. Modern Western medicine really focuses on expelling evil. When people come to see me, I try to support good but when you go to a traditional Chinese medicine practitioner, they do both at the same time, but from a different angle. So they won't say you have stage IV estrogen receptor positive breast cancer, they're going to say “You have decreased spleen qi and increased kidney yang” and they will treat that.

At the end of my questioning the patient before I used to examine them in the old days, I would ask them three questions. “What brings you joy? What are your hopes? And where does your strength come from?” One husband asked if I was interviewing his wife for Miss America. He said “What is this?” But then I met a woman at a conference who told me that her husband had died a few years earlier. And she said, “You know, when we came to see you and you asked him those three questions, he realized that even though he was that far along on his path, that he still did have joy, hope and strength, and that really changed the rest of his life.” So that's what I do in integrative oncology. It's not “alternative.” What I do is integrate complementary and conventional care because after all, I am a conventional oncologist.

Have you had a resistance skepticism, obstacles put in your way by the mainstream in medicine, from both your immediate colleagues and otherwise in integrating this? When I first started, most of the patients who came to see me at the Osher center in 2005 found me on Andrew Weil’s website. But now 15 years later, my colleagues call and say, gee, can't you see this patient sooner than three months? I believe that even though we can't do a randomized placebo controlled trial of integrative oncology versus mainstream oncology, my colleagues at the Helen Diller Family Comprehensive Cancer Center have come to appreciate that patients that we co-manage may do better than patients that they manage alone. Just like I've come to believe that patients that are seen by a traditional Chinese medicine practitioner do better than patients that just see me and their primary oncologist alone.

Yes, there still are people who are naysayers who think that we're all woo-woo and and charlatans, but now we have an established Society for Integrative Oncology. There are a number of journals that publish integrative cancer care research findings. I'm one of the editors of the NCI PDQ Integrative Alternative and Complementary Therapies website, which is a very good website. Commonweal also has the valuable Beyond Conventional Cancer Therapies website. So, there are resources available and there is an increasing database. Oncologists are likely the most evidence-demanding of all medical specialists because we deal with a serious disease and we use pretty potent treatments. So we really demand evidence. Andrew Weil has always said that the degree of evidence should be directly proportional to the potential for the intervention to do harm. If I'm going to say, take this new chemotherapy, your hair is going to fall out, you're going to vomit for three days, and your bone marrow is going to be suppressed, you're going to ask where's the evidence that it works? But if I'm going to say, “Why don't you get a massage twice a month and eat more blueberries and broccoli,” how much evidence do I really need? It's very hard to do placebo-controlled blueberries. That's why I say what we do is evidence-informed.

Let's go back to cannabis or marijuana. How did you first encounter this clinically as a treatment or a palliative measure?

I went to school in the sixties, so I have some experience with cannabis and, as an oncologist in San Francisco for 38 years, the number of patients that I've cared for who have not used cannabis is much smaller than the number who have. I think that's why dronabinol (delta nine tetrahydrocannabinol) was licensed and approved in 1985 as a treatment for chemotherapy-induced nausea and vomiting after the National Cancer Institute and a small pharmaceutical company heard that many patients in the 70s were benefiting from using cannabis at a time when we had very few other agents for nausea. But my experience is that THC is not cannabis because the plant has 400 other compounds in it that

all provide the yin and the yang that balances out the delta-9 THC. When California approved medical marijuana in 1996, I started writing letters for patients to be able to access it. They found that not only is it useful for nausea but sleep, pain, appetite, depression, and anxiety. Whether or not it's useful for treating cancer, again, I've been an oncologist in San Francisco for 37 years. If cannabis cured cancer, I would certainly have a lot more survivors. One of the most painful things I see are people that waited a number of months to see me as a new patient who are treating a potentially curable cancer without conventional care, but with high doses of highly concentrated cannabis products and now they have metastatic disease and can't be cured.

But there have been, at least in vitro, studies that show anticancer activity many attribute mostly to CBD and there’s a big CBD industry now.

I’m not a proponent of CBD, although I tried some last night for sleep, just to see. And it wasn't bad. My patients say that CBD is good for sleep. CBD actually is an antagonist and it changes the shape of the cannabinoid receptor so it no longer could bind THC which is why CBD decreases some of THC’s psychoactivity. The CB1 receptor is one of the most densely populated receptors in our brain. Manual Guzman, PhD, my friend and colleague in Madrid, has demonstrated that THC complexes with the receptor on these brain tumor cells and leads to programmed cell death. In addition, the cannabinoids decrease vascular endothelial growth factor, which allows new blood vessels to form to feed a growing tumor. They also found that cannabinoids decrease the activity of an enzyme that allows cancer cells to become invasive and metastasize. So that's all very elegant, but it's all in the test tube and in animal models. A small study has now been done with an under the tongue spray whole plant extract, modulated to have a 1:1 ratio of THC:CBD. This drug, nabiximols, is licensed and approved in Canada, the United Kingdom and the European Union for treating spasticity associated with multiple sclerosis. It's not yet approved in the US because none of the studies done here have shown it to be effective for anything. But in this study in 12 patients with recurrent glioblastoma multiforme receiving chemotherapy sprayed the nabiximols under their tongue, and nine sprayed placebo. At one year, 83% of the treated group compared to 53% of the placebo group were alive and that was a statistically significant difference. The fact that it's not yet published in the medical literature after first being reported in 2017 is a little bit disconcerting. The study only involved 21 people which makes it less generalizable. But that's the best evidence that we have so far that any cannabis-based intervention impacts a malignancy. So when patients ask me, What should I use, particularly brain tumor patients, I recommend a 1:1 ratio of THC:CBD, but I'm not sure that that's correct, because maybe THC alone would have been better than the 1:1 product. I just don't know.

Finally, how did you get into the “right to die” or physicianassisted dying issue? You published some important research on this issue too.

In those early AIDS days, we had all those gay men waste away and it was truly frightening, and people wanted to have a choice. My colleague Dr. John Stansell called this “orchestrating the good death.” And we figured out that secobarbital with prochlorperazine and alcohol could do it. But I have to say that the number of patients who asked me to do this I could count on two hands. But if you knew what was ahead of you, and didn’t want to burden your partner or family, who were we to deny them, so we would write the prescriptions as requested if it seemed right. Lee Slome, PhD, a psychologist proposed that we survey the Consortium. We provided them with a scenario of a patient requesting assistance and asked “Would you do this?” Then we decided to add “Have you done this?” Those results were published in the New England Journal. We found that the vast majority said they would do it, and over half said they had done so. I didn’t realize at the time that we were ‘outing’ all these colleagues in confessing to a felony.

But on a personal note, my partner who died with me present in 1989 wanted to die at home. His mother came to take care of him one night when I was away, and he fell and she couldn’t pick him up. When I got home she said “He has to go to hospice.” He had the needed medications but had dementia and had forgotten that he had the means. He went to Coming Home Hospice and died there. It was a blessing, and I do believe this is a gift. I am glad we have this option in this state. But dementia is a big issue and currently the way the law is written, dementia disqualifies us from having that right.

At a talk to a large audience not long ago, I asked if dementia patients should still have the right if they have expressed their desires before, and 100% said “yes.”

Well good, that at least means I’m not being so controversial on this topic now! Maybe that’s our next big effort??

You were once President of the national gay and lesbian medical association. How has being a gay man influenced your career in medicine?

Well, I’m not very articulate about this, but I’ve often felt like I was in the right place at the right time in some ways. With AIDS, I was trained in just the right fields when it hit, so what else was I going to do? Even though I think I still have a bit of PTSD from what I experienced in the 1980s and 1990s. Being a gay man in San Francisco wasn’t really an issue – wait, let me say, it took a few times being quoted in the Chronicle about AIDS before I told Randy Shilts that he could say I was gay – and a little tear came down his face. I didn’t have a secure faculty appointment yet so I wasn’t sure my sexual preferences needed to be widely publicized when I was a fellow.

But you wound up a full UCSF professor and chair of a division.

A Professor Emeritus, now, but then again I’ve just been recalled to work part-time in the Osher Center clinic. And I’m really hoping and trying to mentor new people in integrative oncology during this phase of my career.

That, and chasing more total solar eclipses around the planet, right?

Oh yes. But that’s another story.