The Peter Attia Drive - #346 - Scaling biotech and improving global health: lessons from an extraordinary career in medicine | Susan Desmond-Hellmann, M.D., M.P.H.

Episode Date: April 28, 2025

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter’s Weekly Newsletter Susan Desmond-Hellmann is a physician and scientist whose remarkable career has spanned clinical medicine, oncology, biotech innovation, and global health leadership. In this episode, Susan shares insights from her journey training in internal medicine during the early AIDS crisis, treating HIV-related cancers in Uganda, and developing groundbreaking cancer therapies like Herceptin and Avastin. She reflects on her leadership roles at UCSF and the Bill and Melinda Gates Foundation, offering lessons on guiding large-scale health initiatives, navigating uncertainty, and fostering scientific innovation. The conversation explores the promise of precision medicine, the integration of patient care and policy, and the evolving role of artificial intelligence in transforming diagnostics, drug development, and global access to care. We discuss: Susan’s medical training, the start of the AIDS epidemic, and the transformative experiences that shaped her career [3:00]; Susan’s experience working on the frontlines of the HIV/AIDS crisis in Uganda [12:30]; Susan’s time working in general oncology and her transition to biotech where she helped develop taxol—a top-selling cancer drug [26:30]; Genentech’s origins, and its groundbreaking use of recombinant DNA to develop biologic drugs [33:45]; Susan’s move to Genentech, and her pivotal role in the development and success of Herceptin as a groundbreaking therapy in targeted oncology [44:00]; The rise of antibody-based cancer therapies: the development of Rituxan and Avastin [52:15]; The step-by-step drug development process and the scientific and strategic challenges involved [1:01:30]; The ethical and economic controversy surrounding Avastin’s high cost and limited survival benefit [1:12:30]; Susan’s tenure as chancellor at UCSF: leading during a financially strained period, and her strategic approach to fundraising and institutional development [1:14:45]; What Susan learned as CEO of the Bill and Melinda Gates Foundation: strategic processes and decision-making frameworks [1:26:00]; Susan’s philosophy of leadership and how she sought to build an empowering, values-driven culture at the Gates Foundation [1:35:15]; The erosion of public trust in science during COVID, the communication failures around controversial treatments like ivermectin, and the need for better public health engagement and transparency [1:39:30]; The role of AI in transforming medicine: from drug development to cancer detection and beyond [1:53:00]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Hey everyone, welcome to the Drive Podcast. I'm your host, Peter Attia. This podcast, my website, and my weekly newsletter all focus on the goal of translating the science of longevity into something accessible for everyone. Our goal is to provide the best content in health and wellness, and we've established a great team of analysts to make this happen. It is extremely important to me to provide all of this content without relying on paid ads. To do this, our work is made entirely possible by our members, and in return, we offer exclusive member-only content and benefits above and beyond what is available for free.

If you want to take your knowledge of this space to the next level, it's our goal to ensure members get back much more than the price of a subscription. If you want to learn more about the benefits of our premium membership, head over to PeterAtiyaMD.com forward slash subscribe. My guest this week is Dr. Susan Desmond-Hellman. Sue is a physician who is board certified in internal medicine and medical oncology. Her impressive career has spanned multiple fields. She has been a leader in the pharmaceutical industry where she helped develop several

groundbreaking drugs, worked as the chancellor of the health science campus of a major university system UCSF, and served as the CEO of the health science campus of a major university system, UCSF, and served as the CEO of the Bill and Melinda Gates Foundation. She also served on numerous boards of both corporations and nonprofit organizations. She co-chaired the National Academy of Science Committee that pioneered precision medicine

and currently sits on the board of OpenAI. I wanted to have Sue on this podcast to speak about her extraordinary career spanning medicine, oncology, biotech and global health leadership, and to really explore her knowledge on how scientific innovation and leadership can drive better healthcare outcomes. In this episode, we discuss her early days in medicine

training at UCSF during the start of the AIDS crisis before people even knew what it was and the lessons that she learned on handling uncertainty, balancing public health messaging and accelerating treatment breakthroughs. The decision that she made to specialize in oncology and how her time treating HIV-related cancers in Uganda reinforced the need for integrating epidemiology patient care and policy to combat global health crises. We spoke about her transition into biotech, helping develop breakthrough cancer drugs like Taxol, Herceptin and Avastin,

and the role of precision medicine in improving outcomes. Sue talks about her leadership roles at UCSF and at the Gates Foundation, driving innovation in healthcare and global health, and the lessons learned from leading health research institutions and global health initiatives, balancing financial constraints with scientific progress and building culture.

We end this discussion with a perspective on the future of medicine, including AI's role in healthcare, such as the opportunities and challenges in leveraging AI for drug development, diagnostics, and expanding access to high quality care. So without further delay, please enjoy my conversation with Dr. Sue Desmond-Hellman. Sue, thank you so much for making the trip out to Austin. Really,

really was excited to meet you last year. Just an honor to spend part of a day with you and then realize that I could somehow twist your arm into coming on the podcast. I'm happy to be here. I look forward to it. You've had just an unbelievable career. You are an absolute giant in many ways. I love to always give people a sense of how someone got to where they got. So if I recall, you grew up in Reno, is that right?

I did. And you went to high school and college and even medical school all the way through, right? I went to Catholic school for 12 years in Reno. I explain that when people wonder if I was at a casino for my childhood. And then I went to University of Nevada, both undergrad and to medical school.

Then you ended up at UCSF for your residency? You know this, with residencies. My dream residency was internal medicine at UCSF, my first pick, and I got my first pick and went to UCSF as an internal medicine resident. And that would have been what year that you landed there? 1982. Okay, so remind me where we were in the AIDS epidemic

in San Francisco in 82. What was known? If you read MMWR, that's 1981, was the first indication. In 1982, we knew that there was something happening, especially to gay men, but there was a sense it was homosexuals, hemophiliacs, and Haitians. Remember that? Three Hs.

There was so much mystery still involved that I was and my colleagues were in a study to look at drawing our blood to see if we had been infected as a result of treating patients. And what were they presenting with at the time? It's hard for anyone of even my generation. You've never seen a drug-naive patient. All of my experience with HIV,

which was a lot in Baltimore many years later, but everyone was on something. So how would these men present to you as a medicine resident? PAULA FROELICH Numa cistus. PAULA FROELICH Numa cistus carinii pneumonia was the number one diagnosis. So that's what you saw in the hospital that brought patients to attention. It was a disease that immunosuppressed patients could get very rarely. Most clinicians had never seen it before. What was also clear is that there were many other infections that were not as obvious

or life-threatening as pneumocystis was when we saw it right away. What was interesting from an outpatient perspective was Kaposi sarcoma. Tell folks what that is. Capsi sarcoma is a really unusual purple colored tumor, very visible externally, it caused nodules. In patients with HIV infection, it also caused internal organ involvement and patients would cough up blood or they would vomit blood. But what was really sad and difficult is the combination of cachexia and Kaposi sarcoma meant that everybody knew you had AIDS. They sort of wore it. And what was interesting for me was that this old-fashioned Kaposi sarcoma was

fundamentally different than what we were seeing. We also saw non-Hodgkin's lymphoma in numbers much smaller than Kaposi sarcoma. But Kaposi sarcoma was a very big problem in San Francisco. It was very common in gay men and it was common in the population we saw. Adam Fossum And was there ever a sense of fear among the medical staff that we don't know what this is, we don't know how it's transmitted, and therefore we don't know how to protect each other or ourselves or other patients for that matter. It's hard for me to imagine that given how much we take for granted today.

I think it's probably a reflection of my own personality and my own wish to be a physician that my memories of those days are much more about sadness, about my patients, and about people my age dying or being pretty clear they were going to die. I mean a story that brings it to life is many patients started selling their life insurance because they were sure they wouldn't live long enough and they wanted the money now and then when the antiretroviral therapy came along they wish they hadn't which is a good thing to have. But I was just really sad. There were fears about the residents and about contagion, but in San Francisco

there was such a wish to help the patients and such a good spirit about playing a role in helping that we all persevered. But the first patients I took care of in the hospital, I remember very well in 1982, we were gown, gloved, masked, had a cap on. It was like we were going into an operating room. Got it. For all intents and purposes, you were acting like this was Ebola without knowing. Absolutely, absolutely.

And so you finished your residency in internal medicine. Did you go directly into your fellowship? I did a chief residency at the University Hospital, and I think that was the first that I knew I really liked managing. I really liked interacting with people and helping people succeed. So I did that for a year,

and then went into my oncology fellowship after that year. And why did you pick oncology? Oh, to this day, I love oncology. If you love medicine, and I do, and you love patients, and I do, it's the combination of you get to call in your compassion gene and your nerdy science gene. And when I was in Reno at the Reno VA, I had an attending, Stephen Hall, and he was the oncologist who was teaching me about medicine, third year medical student.

And I loved everything about how he showed up. I loved his compassion, I loved his intellect. And after that, I had in my mind this bug about I wanted to be like him. I can really relate to that. When I was in my third year of medical school, I went to the NCI for three months with Steve Rosenberg. Oh.

And it was the exact same experience. And I remember learning many lessons from Steve. One of them was that cancer diagnosis, and of course at the NCI, as you know, nobody's showing up with stage one, two, or three cancer. By definition, every patient there is showing up with metastatic cancer and they've progressed through all standard treatments. So these are people that have six months to live and maybe 10% of them you actually come up with a durable remission for. But he said, look, cancer will do one of two things to a family. It will take a strong family and bring them much closer together. It will take a fractured family and blow them wide apart. As a doctor, as a nurse, as in anybody in the field of oncology,

your ability to kind of be there for that family is as important, potentially more important than it is in any other specialty of medicine. That's really well said. I love that. So, tell me a little bit about the state of oncology in the mid-'80s when you're embarking on your medical oncology fellowship. Help people understand what the world of cancer looked like roughly 40 years ago.

Let me talk about breast cancer. That's a cancer that is such a good example. The common therapy that was used, Cytoxan, Methotrexate, 5-FU, were very old, decades old. There were no new chemotherapy drugs. It hadn't been in a while. The field was stifled, I would say, in terms of medical oncology. There wasn't a lot going on. I was

really interested in cancer epidemiology. That was something to me that asking the question, why did people get cancer and couldn't we do something about it seemed really important to me. I wanted in the second year of my fellowship to study the relationship between hepatitis B and hepatocelular carcinoma and to understand that better and to think about the viral link with cancer. The mentor I was supposed to work with ended up not coming to San Francisco.

So I decided to go to Berkeley and get a master's in public health as a backup strategy. I really scrambled because I didn't want to waste a year. What was the nature of the program? It was a three-year fellowship with a research track on the side because obviously UCSF is such an academic place. It's a very academic place, but you could do two or three years and many people went into the lab.

I didn't want to go into the lab. I wanted to do epidemiology. I wanted to learn more about statistics and epidemiology. I thought I wanted to do it because I wanted to be a cancer epidemiologist. And to this day, I still think that is one of the great opportunities to make a big impact, but you have to be funded.

So I'm a pragmatist. The good news was that all that learning at Berkeley and at UCSF in epi and biostat, I brought to drug development. Clinical trials have a lot in common with doing epidemiology. You brought up the example of hep B and hepatocelular carcinoma.

Was it understood at the time what we now know? It was, yeah. Palmer Beasley, one of the fathers of that relationship was the guy who was supposed to come. There were preliminary papers and something relatively early, but it was emerging science. Do you recall what the incidence of hep B was and hep C back then?

You know, I don't. If you weren't in Asia, it was actually, I think, and you know, I don't if you weren't in Asia It was actually I think relatively low but I believe increasing was just partly why the vaccines are so important Tell me about how you wound up in Uganda After I got my masters in public health I became the oncologist at UCSF in the university hospital for the AIDS clinic. This is Moffitt? This is Moffitt.

So San Francisco General had a very well-known program run by oncologists for AIDS patients who were in the safety net hospital. But in the university hospital, if you were very sick and you had Kaposi's sarcoma, you saw me. And my husband, because we had just gotten married, we were interns together. He was in the lab in ID doing immunology work. So two of the chiefs of medicine at UCSF were approached by the Rockefeller Foundation, who had started to become worried about heterosexual transmission of HIV. Remember I talked about the Haitians and the hemophiliacs and homosexuals? One

age wasn't heterosexual. And so there was a lot of disbelief about African HIV. And in fact, some people thought it must be gay sex, but people are too embarrassed to admit it. There were other theories, but people just did not understand what was going on in Africa. So the Rockefellers said, we'll give you a grant at UCSF, we'll grant you money to study heterosexual transmission of HIV. And this was through an epidemiologic contact tracing lens, not necessarily going into the lab and trying to figure this out. Not going to the lab, but really looking at epi. And particularly, there was a hypothesis that if it was heterosexually transmitted, there was something to do with sexually transmitted diseases. And that there was a hypothesis that if it was heterosexually transmitted, there was something to do with sexually transmitted diseases and that there was something about

increasing your risk if you had untreated STDs, sexually transmitted diseases. So we were asked to go. UCSF had no global health. To put this into context, we had a flat and two Honda Civics. I still remember this. We gave my dad power of attorney, we sublet our flat and we sold our Hondas and moved to Uganda.

I'm laughing in part because I had never been east of Chicago. I mean, this was a pretty dramatic thing to do and it was only- And I'm sorry, you, your husband and who else? The two of us, that's the team. That's the dream team. That's the team, that's the team.

And Uganda was a place where, on the positive side of things, the NCI had set up a collaboration with Uganda Cancer Institute, where they did some really great things in lymphoma and Burkitt's lymphoma, if you remember those stories, and one of the physicians at UCSF had been associated with that, John Ziegler.

So there was a connection to the Uganda Cancer Institute. So on the good side of things, there was that and there also was and is the Ntebi Viral Institute. So there was some infrastructure there. Unfortunately, most of that infrastructure had been ruined by the Idiyaming regime not long before we went to Uganda. So when we went there, it was pretty lawless. There were roadblocks you had to stop at. It was difficult to live there. It was really difficult.

And what about safety? I would say now that I'm used to being in more safe situations and older and wiser, it was probably not that smart the way we lived there, but we weren't reckless. It was probably not that smart, the way we live there, but we weren't reckless. It seemed dangerous when you were in the car to have carjacking or your money go missing or things like that.

Was Idi Amin still ruler? Idi Amin was gone, but when we were there, he made that attempt to come back from Saudi Arabia and go back to Uganda, but it was thwarted. So that was good news. So Nick, my husband, reestablished the sexually transmitted disease clinic and attended in the internal medicine ward.

And I like to say I doubled the population of oncologists in Uganda when I was there. So my colleague Edward Mbitty, who's Ugandan, put all his focus on the pediatric unit, and, put all his focus on the pediatric unit, and I put all my focus on the adult unit, which was so many cases of Kaposi's sarcoma. Can you give me a sense of what this meant? So we're talking late 80s now. This is 89, 90, and 91.

Is AZT out yet? Not yet. Just on the brink. Okay. So we have nothing. And what is the approximate conversion? So for a patient who develops AIDS, what fraction of those will go on to develop KS?

If you were in Uganda at the time, gosh, especially amongst males, but also males and females, it's so hard to give those numbers. But I would say about a third of patients who sought medical attention probably had KS, some KS. What was the prevalence of HIV AIDS in the population in Uganda? Depend on the population you treated.

It was double digits in the country as a whole. If you were 16 years old, if you were a 16-year-old girl and you went to the STD clinic, you had a 50% chance of being HIV positive. 16, and most of those girls, it was their first and only sexual partner. It was Russian roulette to have sex in Uganda then. I mean, Russian roulette's one in six if you've only got one bullet in the chamber. This is brutal.

You got the bullet in one of the two chambers. Yeah, yeah. And the best business in town, coffin maker. We would go, we would drive back to where we stayed and you would see, if you've ever been in an African village, like they'll prop up the coffins made of wood and you just see them because that was so stunning. The feeling of being scared and sad in San Francisco

in 1982, multiply that by a thousand in 1989, it was terrifying. If we hadn't gotten ARVs, this was killing people. But you know, the same time, the first time we went back to San Francisco from Uganda was six months after we had left. I went back to the Kaposi sarcoma clinic that I had led and said to the nurse, oh, you ask about your patients. I had so many great guys who I cared for. All my patients were dead. All of them. Six months. The sense of how bad HIV was before antiretrovirals, it's impossible to overstate it. Just impossible. And when

we were in Uganda, it was really clear that you could see someone's immune status with a good physical exam if they had Kaposi sarcoma. I wrote a paper that I think is a good paper if you do global health and you have limited resources. It was a paper that had one observation. If you had Kaposi sarcoma on your soft palate, on the roof of your mouth, you had HIV, 100% predictive. Kaposi sarcoma, there's a Mediterranean form and an African form. It happens on your skin, it can cause elephantiasis,

but it doesn't go in the mouth as just a surrogate for your GI tract. It doesn't happen unless you're immunosuppressed with HIV. These patients weren't necessarily dying from the KS directly. That's a proxy for how weak their immune system was. I assume they were ultimately dying from a pneumonia? Many would die from pneumonia. There was severe cachexia, and then they were prone to pneumonia and other problems.

But capicyc sarcoma in the lungs or the stomach can also cause bleeding, and you can die from that. What did you know at this point in time about HIV? Because the virus had been identified by this point. What was known and what was unknown? We knew most of the clinical syndromes associated with HIV. Gallo? Was it Gallo?

Yeah, Bob Gallo was one of the, Luukman Yeh was, they had a fight over who deserved the credit. But yeah, we knew about HIV then. And we knew the biology. And we knew as soon as we got to Uganda and examined patients that this was heterosexual transmission of HIV. And we knew that untreated STDs were a big reason.

And that was a very important thing. Adam Felsenfeld Going back to these 16-year-old girls, is the reason that the heterosexual transmission was so high because the viral loads were through the roof? Because today, if a male with HIV had unprotected sex with a female, it would not be that high, would it? It wouldn't be that high, no.

So one of the really important aspects of STDs is high frequency of herpes and chancroid, really open lesions that are very, very, if not treated. So it's the one-two punch. Yeah. Super high viral load. High viral load and transmissible. And opening.

Yes, yes. So we knew all of that. Now, we also knew that some of these were treatable, that both medication, also Museveni, the still leader of Uganda, had this very funny campaign called Zero Grazing. So they raise a lot of cows and this is very important in Uganda is having a herd of cows. It means you're an important man, you know.

Musevenio wears this hat like he's raising cows. So Zero Grazing, the farmers and many people knew what that meant. One wife, one partner, no grazing. And so there was a pretty good public campaign. We did a lot of condom distribution. Adam Benz And so the government was receptive to this. Dr. Sarah Pletka Yeah. Adam Benz They understood the science.

Dr. Sarah Pletka Oh, they knew. Adam Benz They understood the epidemiology and they were completely on board with the campaign. Dr. Sarah Pletka They were very on board. They also knew that this was going to be a geopolitical problem for them if people were dying in the prime of their lives at the rates they were. They got that. This was really clear to them.

JS What other countries in Africa were afflicted to this extent? AMT In East Africa, there was quite a bit, there was a lot of HIV in Kenya and there were programs like the one that we had in Kenya, Tanzania. There were others where it was more unknown, I think not talked about. I mean, the program I know about most today is the program my husband's been working with for 15 years, which is

Elizabeth Glazer Pediatric AIDS Foundation. They work now, I think, in 12 countries in Sub-Saharan Africa, and many of the southernmost countries are heavily affected by HIV still. Can you estimate in a year how many people died from AIDS in Uganda when you were there? Oh, no, I can't estimate it.

I guess the point is it's a staggering number. Yeah. And yet there were so few of you that were on the front lines. If there's 16 million people, it wouldn't have surprised me if there were a million people who died. I mean, it's that kind of numbers. I'm probably exaggerating, but not by much. And I think the sense of feeling overwhelmed

is just really important. What I realized I was doing, I don't know if you've interacted with people in the military much, but if they were on the battlefield, they triaged. I triaged. I triaged in San Francisco. If you didn't need chemotherapy,

but you had Kaposi sarcoma, I didn't see you. What was the chemo? The simple one was vincristine. Vincristine's actually reasonably good against KS. I used it in Uganda a lot. It does cause some neuropathy, but if you're careful about how much, and then bleomycin, again, you have to be careful

because of the pulmonary toxicity. Good old-fashioned, vincristine and bleomy much, and then Bliomycin. Again, you have to be careful because of the pulmonary toxicity. Good old-fashioned, Vincristine and Bliol, and then Texel. Texel was approved for Kaposi sarcoma after I left Uganda. It wasn't a drug before then. I would see the patient and I would literally ask them and their family, can you walk? If you can walk.

If yes, you're too healthy for me. You're too healthy, it will delay. There was triage, because I only had on the shelf a certain amount of chemotherapy. How did you manage the personal toll of the grief and the death of seeing this? I mean, look, I think every doctor, to some extent, goes through this,

where you try to sort of compartmentalize what you're seeing, but the truth of the matter is, virtually no doctor can really comprehend what you are describing there. How did you process that? I have this philosophy, which I don't recommend it for others. It's just my philosophy.

I love people. I love interacting with people. I love getting to know the patients who I care for. And it makes me happy to think I'm helping. Helping might be helping them get better. Helping might be helping with their pain, or they can talk about dying with me because it doesn't make me scared.

So I get a lot of joy in trying to contribute, even if I feel overwhelmed and if I step back and think how can we cope with this? My coping is- Is leaning in. Yeah. Does your husband share that? Was there a yin and a yang to the relationship where you supported each other in a way that

was helpful in that? I do understand what you're saying and I appreciate that there is a joy that comes from helping people, but I can also at least personally say that there are moments when it breaks down and you feel so overwhelmed by sadness. Well, first of all, my husband is more introverted and probably gets more sad, but we are also a good team because we are there for each other. And I think it's a special thing done in small amounts,

not too much, to be able to come home and say, boy, that was tough. Here's what I dealt with today, or I need to tell this story or I want to talk about this. The other thing we did, which is I think so important is I do drive a lot of joy in trying to help, but I'm not a martyr. I don't believe in it. Okay, you worked hard, I worked harder. You suffered, I suffered more. I hate that. So we went to Greece. We still laugh about going to Greece and eating our way through Greece for a week.

When we were in Uganda, we had a couple other good trips. We went on a hilarious safari to a place that was Moya Lodge that had been closed to all tourists had just reopened and it was so great. We saw hippos and elephants and we realized we were the only, what you call in Uganda, Amazungu, which is a white person there. So it was a grand adventure.

So we had some grand adventures and played tennis, enjoyed friends. We did as much to keep our spirits up as one can. And so you came back to the US after about three years. Uh-huh. And did you go back to UCSF? Well, we wanted to go back to UCSF, but we had not kept our academic careers going as much as we should have. We didn't publish enough, and they

didn't have a global health program or money for us. Taking care of a million people with HIV wasn't enough to justify coming back to UCSF. It actually wasn't. So we said, well, gee, when the chief of medicine outlined for us the plan for us to stay, a large part of it was taking care of patients to pay our way. So we said, boy, taking care of patients,

we know what that looks like. So we went into private practice. In San Francisco? No, we moved back to Kentucky where Nick is from. So we moved back to Kentucky, and I was in a two-person oncology practice with a former classmate of Nick's in Lexington. And you were doing, at this point,

oncology unrelated to, not necessarily focusing on HIV and AIDS-related cancer, breast cancer. I was doing good, old-fashioned American oncology. I didn't take my oncology boards when we went to Uganda because I was in Uganda. So I still sort of laugh about taking the Davida oncology book with a yellow Sharpie. I reread the big oncology book twice. Is this the Davida Hellman Rosenberg book? Yes. Yes.

Yeah, yeah, yeah. Of course. Yeah, it's brown these days, I think. I rere-read it twice, took my boards, and did fine. So I was ready. This is unbelievable. So you're sitting in Kentucky, practicing garden variety oncology. Talk to me about what that's like. I mean, that's completely orthogonal

to what you've been doing for the past couple of years. It was so, so, so, so different. And Nick was in a practice where he was more like a hospitalist. Somebody would get a fever in the ICU and they'd call that ID group. And my practice was a two-person practice. It was very classy.

I saw a lot of lung cancer. It was Kentucky. So there's a lot of smoking, a lot of people from Appalachian. I actually like taking care of patients. So that part I liked, but I really missed intellectual research, collegial stuff that I was used to at UCSF,

because we had been there nine years by that time, because we were still UCSF faculty when we were in Uganda. Nick was called about Bristol-Meyers Squibb search for an expert on HIV, because they were trying to follow AZT with the next antiretroviral. I think it was DDI and D4T were both in development then. And so they recruited Nick to come and work at Bristol-Meyer Squibb out of private practice.

And Nick said, I won't come unless you have a job for my wife. And they said, no, we have a nepotism clause. We don't allow couples to work at Bristol Myers Squibb. So he said, fine, I won't come. He's a good husband. This is one of our favorite stories because it's a true story. So they called him back and they said, we really, really want you to come because we

want this program to do well. And could your wife be a consultant? Would she agree to be a consultant and not a full-time employee? And he said, yeah, that'll work. So we moved to Connecticut. He had a job and I was the trailing spouse. And I can just see what this looked like. I'm making this up now.

Oh, God, we've got an LMD. You know what an LMD is. We got this lady from Lexington, Kentucky. She's in private practice oncology and we're stuck with her. Let's have her do drug safety on Taxol. We have this new drug and it's really busy, it looks like it might work, and so we'll put her on drug safety. She can't hurt anything doing that.

So... But did they not understand what you had spent the last couple of years doing prior to being in Kentucky? Did they not know what you had done in Uganda? I don't think that registered, because there were so many people there who were very traditionally trained at NCI, or at Yale, or wherever they were, and they were traditionally trained in oncology.

My experience in Kampala in Uganda didn't make an impact, but here's what was funny. Nick and I didn't have a statistician. As I told you, we just, the two of us went. So we brought this little compact computer and all the SAS manuals. We didn't have a TV. We didn't have newspapers.

We didn't have anything. So we taught ourselves how to do SAS programming. When I got to Bristol-Myers Squibb, one of the really interesting things about Taxol is it causes severe neutropenia. But it's short. It's like this short, severe neutropenia. And so I wanted to study that because I

thought it was really important in why people weren't really getting infections. I always have to remind myself, tell people what Taxol is, how it works. Just give them a quick, what is neutropenia, why would we care? When I talked before about how few new chemo drugs there were, Taxol was one of the first new chemotherapy drugs.

So, Taxol is a product of the U-tree, and it's a microtubule poison. It is, if you think about it coming from the U-tree and you think about sap, think about trying to dissolve sap in water and give that to a patient. That's plenty hard. The dissolving fluid that's given with Taxol.

And the reason we would give somebody with cancer a microtubule inhibitor is because that prevents cells that are dividing. You can't divide. They can't, they need these microtubules when they create new cells and we wanna block that. And we wanna block that. So this was not just a good way to block cellular division which is so important in cancer therapy. It's

really important because it's very different than some of the old chemotherapy drugs and if you're resistant to those old drugs, here you have a brand new mechanism of action. So that's a terrific thing. But it's not easy to dissolve it. So the dissolving agents are like soap, they dissolve the Taxol, and when the National Cancer Institute tried to use it, some patients got severe allergic reactions from that, and they got scared and put it on the shelf.

So Bristol-Meyer Squibb went to the National Cancer Institute and said, you know, that drug might really be active. We're willing to carefully go back in the clinic and test it and give people agents to counterbalance the allergic reactions and see if we can get away with it. So they did that and they got an approval in ovarian cancer, a brand new agent. Now, Taxol was really exciting because first ovarian

and then breast cancer were these indications where we had not had new drugs or really any drugs that were active in the case of ovarian for a long time. And because I was the safety person, I was really trying to understand and put into context all these safety issues so it was possible to safely treat patients with these drugs. It had already been approved.

It had been approved for ovarian cancer when I showed up. So now you're doing post marketing surveillance on safety. We're doing post marketing surveillance on ovarian and putting together a US submission and a European submission for breast cancer. So I started talking to the statisticians there about how I wanted them to program to get the data we needed for the safety label. And I'll never forget the guy looking at me and saying, do you know how to do this? And I said, well, I had to learn in Uganda because I didn't have somebody like you, you know.

So it was sort of funny that I was very happy to prove myself. It didn't bug me. It made me more feisty. Like, I'll show you, I'm not underdosed in the kinds of things you need to do in this place. And by the way, I loved every minute of being at Bristol-Meyer Squibb. They were pros at cancer drug development.

They were pros at monitoring safety. And I thought it was so much fun because you got to make drugs. What was the pharma landscape like in the early 90s? So you had Bristol-Meyer, you had Pfizer, you had Merck. You had Merck, you had Novartis. I think Novartis was a combo of a couple. It was smaller, much smaller,

and cancer was Bristol-Meyer squib. I mean, they had made cisplatinum, carboplatinum. They had a lot of those drugs, and people who had made those drugs were still there. And I was really happy to learn from them. I felt very lucky to get to be around these folks who knew about Taxol. So we got Taxol approved in the US and in Europe

for breast cancer, became Priscilla Mosh Squibb's number one drug. I became the project team leader for Taxol. How long did it take them to thank your husband for forcing them to bring you along? Ha ha ha. Too long. He really enjoys that story because he,

like all good family stories, it gets embellished over the years and he tells this story like, you should actually want her. You don't know this, but you should. He's a good husband. When you pause at where we are in this story, to think of everything that would come from this moment forward,

and to realize there's a scenario under which nobody knows everything that's about to happen, and you're an oncologist in Kentucky right now. That's right. That's right. I'd be better at tennis. Yeah. I had more, I had more free time. But yeah, no, I think that's the thing that I love to mentor.

I think it's really underrated to listen to students and hear what's on their minds. And I remind students about the role of serendipity. And I think I'm a poster child for the role of serendipity. So you left Bristol-Myras Squibb in 95? 95. And you went to Genentech. Tell me where Genentech was in its life cycle then. So Genentech had been around for a while. I mean, when did Genentech get founded?

In the mid-70s? 1976. Okay. Give folks a little bit of a history of Genentech. Genentech's a storied company, but also a different company in that it was founded on a new technology. Genentech's a really interesting company because it claims to be the first biotech company. There's some Cetus back and forth about that, but it was based on genetic technology. That's where the Genentech name came from.

And what Herb and Bob, the co-founders of Genentech, wanted to do is kind of do a proof of concept that you could use genetic technology and make medicines, make big medicines, proteins, antibodies, medicines that would almost certainly have to be injected rather than swallowed because they're large and they're proteins, so you break them down if you swallow them. But their initial goals were focused on insulin, which they out licensed to Lilly and Pfizer, and growth hormone, human growth hormone. So before Genentech, when you were a parent and your child was short, you needed to give that child growth hormone that came from cadavers.

And that had a risk of this slow virus disease and that was not a good trade-off for parents. So the concept of having recombinant, of having human-like growth hormone was a really wonderful thing. So Genentex's first drug was human growth hormone and it was a tour de force. It was really amazing that in the late 70s they were able to do this fermentation and purification because they had to prove to FDA it was pure human growth hormone with no contaminants. And it became famous for that and people were excited and thought this was cool.

Soterios Johnson Tell people briefly how this worked. What was recombinant DNA technology? What were they putting the gene into? How did they get the gene to make the protein? We take this all for granted today because we have... It's tricky, yeah. Yeah, but it's so incredible. So what you see if you go to Genentech or a company like Genentech is you see these tanks and the tanks are like a cell ICU, like an ICU for a cell. So the cell, what you're doing is you're teaching the cell

to make at very high amounts growth hormone, way higher than your cells or my cells would. And then you're teaching the cell through this genetic engineering to secrete it into a medium, into this soup that is really a lot of growth hormone, and then you're taking away the cells after they secrete it. You're purifying that growth hormone, and you put it in little vials.

And that's the process of biotechnology. And you can trick a cell into making almost anything you want, not completely, but almost anything you want, and make it very much like human, which is neat. So you don't have to go to a human to donate you growth hormone because it would be too small. Or in the case of insulin, I mean, they were using insulin from pigs and- Porcine insulin that made allergies and expensive. So human insulin really changed how you thought about treating people who have diabetes. So Genentech made growth hormone and Genentech sold growth hormone and

set up something I actually think is a really neat thing that Genentech did, which people said, how do you know that by giving kids extra growth hormone, it won't cause leukemia or a fourth arm to sprout out or so, you know, weird things to happen? And Genentech said, well, we'll follow every child. So they set up a patient registry, one of the first patient registries ever, and followed every child until they reached their final adult height. And the physicians and their staff entered this into a computer.

And so this is an amazing amount of information. So if the FDA ever asked us, do you have this with growth hormone? Did you have that with growth hormone? We had not an example, you wouldn't even do statistics on it. Every child ever treated with Genentech's growth hormone. Do you have a sense of how many kids that was?

Oh, hundreds of kids, thousands of kids by now. Yeah, yeah. So Genentech got really good at that. And in fact, when I went to Genentech in 1995, the chief medical officer of Genentech was a pediatric endocrinologist, an expert on short stature and growth hormone. But it's a pretty small market.

This is uncommon. By this point, it was being used rampantly in sports. Yeah, and the FDA was not happy about that and pushed really hard on Genentech to control that use. Was it being used by this point also pretty heavily in HIV, right? People were using it in HIV, they were using it in sports, anything where you wanted to have more muscle mass. That's exactly right.

Genentech had done some studies to look at whether that was a good idea and none of the studies came out successful. Meaning there was no benefit to an HIV patient being on growth hormone? The benefits did not outweigh risks of having increased blood sugar and some other things that would happen. So one of the aspects of Genentech

that happened in the early years before I was there is they learned how to make enzymes. Same genetic technology, telling the cell make these enzymes. And some of the enzymes actually got out licensed to make commercial enzymes like the EUs when you wash clothes and things like that. So that wasn't core to Genentech.

But they had an enzyme activase, a TPA, tissue plasminogen activator, that could break down blood clots. Did they go after that knowing what they were doing, or was this a bit of a fishing expedition where they realized in the process of trying to do many things that, oh my God, we can actually make TPA,

which you're gonna explain in a minute why that changed the game of cardiovascular medicine. It was intentional. They had a really great, there's a clinician researcher, Dave Stump, who is a clotting expert. He's hemonc on the heme side. He was there and really pushed them to do this. And the concept was that if you could break down the blood clot, you could cure the heart attack. You could

save lives. And the interesting thing, if you are interested in doing trials, is they started the concept of a large simple trial. This was early on and people in cardiovascular, Gene Brunwald and his followers had started these large simple trials. So Genentech kind of bet the farm on this TPA. And the farm was that they could change the outcomes in 30 days. There'd be more people alive than dead if they were treated with Activase. And two of the people involved in 30 days, there'd be more people alive than dead if they were treated with activase. And two of the people involved in the studies, you probably know their names,

were Rob Califf and Eric Topol. Was Eric at Scripps at that time or where was he? I think he was at the Cleveland Clinic. And they ran a group called the Timmy Group, and they did all these studies named Timmy. And so they did this big trial and it worked. If you treated with Activase you could break down the blood clots. So Genentech started this franchise in cardiovascular

and again did this really interesting patient registry to look at 30-day outcomes for post-marketing. But stints came along. And so the franchise of Genentech and people who were treated with TPA really went down. And the stroke indication was tricky. You had to make sure it wasn't hemorrhagic or you could make things so much worse. So fast. Yeah. And so the stroke indication on paper was really cool, but pragmatically was really tough for hospitals to execute. Genentech also made another enzyme-like molecule, DNase, Pulmozyme, for cystic fibrosis.

And that was approved very tiny. It decreases how thick your secretions are, but with vertexes, CF drugs, it's also been scooped. So when I came in 95, Genentech was really struggling. They had those three drugs. They had growth hormone, TPA, and palmazine. Why did they outlicense insulin?

I think they needed the money. Got it. I don't think they have the scope to even make it. And why did you decide to leave? Bristol-Meyer Squibb is just crushing it. You finally earned the respect you deserve. You've got this struggling company, Genentech. Was it the opportunity? Oh yeah, yeah, for sure it was the opportunity. I will tell you, if you were me in 1995, sitting down with Art Levinson,

and he was the head of research then, and he was talking about the future and oncology, what the plans were, you'd have gone too. You'd have got to. For sure it was an opportunity. We were doing well. I will say that further down on the list of pros and cons was West Coast's home.

I mean, Connecticut was snowy and cold. I didn't come over on the Mayflower, it turns out. I mean, I loved people at Bristol-Meyers Squibb. I loved the job. But heading back to San Francisco. And I loved being in San Francisco, yeah. That was a big deal. But I believed Art when he said,

we're gonna be a cancer company. So what was the first thing you worked on? Ah, thrombopoietin. They hired me to work on thrombopoietin. It was going to be the third leg of the stool. EPO, so make your red cells go up. Neupogen for your white cells and TPO for your platelets. And it was a big race.

Amgen was in the race. Who developed EPO? Amgen. Amgen, okay. EPO and Nupagen. Got it. Amgen and Genentech had always been kind of rivals. And when they cloned ThromboPoetin at Genentech,

I read the paper and then they called me, did I wanna come work on it? It was that kind of thing. When you clone it, if you publish it, that doesn't give you the right, it's a race for everybody. It's a race. So let me ask a silly question. Why do you publish the results of the cloning

before you've gone and made the recombinant protein yourself? So you patent it, then you publish, then you make the recombinant. OK, so once it's published after the patent, you get to make it. Genentech, one of their great assets started by Herb Boyer is they publish. They don't stop the scientists from publishing. They get the lawyers in there quick and they make sure that they protect the IP of the

company, but they want people to publish. Very academic. So thrombopoietins, EPO and neupogen are as if you design them to make recombinant forms and give them for cancer patients or other patients who need them. Thrombo-poetin, not so much. To make it simple, if you said, okay, your platelets are going way down from your chemotherapy and I'm going to give you thrombo-poetin to make them go up, they come back up really late and they go too high. to make them go up, they come back up really late

and they go too high. So I'm making you at risk for a blood clot by giving you a million platelets, but later than you need to and you're recovering on your own already. Was that known only once you started developing and you understood the kinetics of it? Once we looked at how it worked in patients,

we knew better than we had before. The kinetics of really recovering from, not all chemotherapy, as you know, causes your platelets to go low. Yeah, so you can't give it prophylactically because you don't know who's gonna get thrombocytopenia. Right, right. And this tricky thing about going too high,

if you're wrong, it's a problem. What do you do, you plasmapherese the patients if you've overshot? Or not plasmapherese, platelet-pherese? You could platelet-pherese them. I mean, there are remedies, but you don't wanna do that. Anyway, so thrombopoietin proved to be very, very difficult drug,

and I learned a lot about the cancer equivalent or the product development equivalent of tulip mania. When everybody's so excited, you get excited too, and it's like, oh, I did learn a lot. I've often reflected on what might happen that I'm not thinking about now. But what also happened is the labs at Genentech had been working on Herceptin, on Trastuzumab for a while.

Art became the CEO, Art Levinson became the CEO in 95, and he wanted to push on having Trastuzumab Herceptin get into the clinic. Tell folks how that drug worked, what it was for. Trastuzumab, or I'll call it Herceptin because it's less of a mouthful, is a antibody. Like you and I have antibodies that fight disease in our bodies.

And it's an antibody that targets this protein called HER2. And HER2 matters because about one in four women with breast cancer have too much of it. And when you have too much of it, if you've got too much HER2 from the time you're diagnosed, your median average survival is three years. If you don't have too much of it, it's seven years.

So you know it matters. So the concept with this antibody is turn that off. Whatever bad thing that drives it down to three years, turn that off and go back to seven years. Pretty simple concept. Why do you, mechanistically, do you think that the overexpression of HER2 was impeding immune clearance? What was the thesis at the time

for why overexpression of HER2 was cutting life expectancy down? The thesis was that it was telling the cell to grow. That it was giving a growth signal to the nucleus to say grow more. And if you could shut that off, you'd grow less. Now later, we armed Herceptin, we put a payload on it. So then you could say, both change the grow more signal

and you've got a little bomb on there. You kill yourself. Yeah, kill signal, yeah. So you'd get a twofer. In fact, another company has one AstraZeneca that's so powerful with a bystander effect, you don't even have to have overexpression. So that antibody, I'm talking about it now because anybody in breast cancer knows about her too.

Of course, yeah. You see it on TV and direct to consumer ads. Yeah, but I think what I really enjoy about this type of discussion though, Sue, is one, it's the story of your career, but it's also the story of oncology. It is, yeah. It's the story of modern oncology. So you're one of the few people whose careers takes us through the walk of modern oncology. I mention that because it seems impossible.

There was a lot of people at Genentech who were negative about Herceptin. Did not think we should invest. The dogma was that antibodies were all hype. They'd been over-promised as smart bombs, smart missiles, Time magazine, all of this, but that they had flopped. What was the biggest failure at that point commercially?

I don't think the things had even been commercialized. I don't think they had gotten out of the clinic, that people just weren't seeing benefit. I have a very good friend who's an oncologist, and he said you just can't treat a solid tumor, a solid tumor versus leukemia or lymphoma with an antibody. You need something more powerful. And remember what was happening at the same time is if you want to talk about the history of oncology, the

amazing thing is being at ASCO, the American Society of Clinical Oncology, and two different rooms. One room, we hear that Herceptin is going to change forever how we think about antibodies and breast cancer. Way better than we thought, improved survival. The other room, doing bone marrow transplant for breast cancer and having the South African group who published a paper saying it worked, retract the paper and go through

and talk about how much of it was fraudulent, fraud, fraud, fraud. So at the same time, this nearly toxic, nearly lethal bone marrow transplant for breast cancer was debunked at the same time as we said what we call now a naked antibody, no payload, no chemo. You give her septin, you're gonna help that patient with breast cancer, just an antibody.

Welcome to modern oncology. It could not have been more clear. I almost forgot the BMT stuff. It's so archaic. And it was a distraction because people felt like you just needed to hit the cancer hard. You just needed to hit the cancer smart. Hard wasn't the point. Yeah.

I mean, we've got to be getting close to Avastin now too, right? Yes. But don't forget Rituxan. So when I said people didn't believe in you could treat a solid tumor, they thought you could treat lymphoma, because we did. Antibodies were so disliked. People did not believe in antibodies that in 95, 96, IDEC was gonna run out of money.

So IDEC had made an antibody to CD20, a very important marker on all lymphomas. And they were getting them out of money. So some of our business development folks talked to them about Genentech doing a deal with them on rituxan. It is impossible to overstate how important rituxan is in lymphoma. I often think when I'm in product development of patients I've cared for,

I had this great 83-year-old pharmacist when I was in practice, and he had a lymphoma that was low grade, a little tired, he was fine. And so we did watch and wait, my not favorite strategy of oncology. Let's watch and wait as you dwindle. He'd be a perfect candidate for rituxan. Four doses, you can repeat it. In fact, it works so well.

Here's when I changed my mind on antibodies. Somebody runs in my office and said, oh, we have a case of tumor lysis syndrome. So tumor lysis syndrome being somebody got rituxan, they had a lot of lymphoma, and the cells are breaking down so fast their kidneys can't keep up and they have to be dialyzed. Oh, that's only an antibody. No chemo, no payload, nothing. That's when you know you've got a good drug.

How many cells in the body, how many types of cells in the body express CD20? It's mainly a B cell. But it's not as specific as CD19, is it? I think 19 and 20 are both B cells. I'd have to look at it to see. I know CD19 is on the B cell, but I didn't know the, okay. We were talking about this earlier. This is chimeric. It's chimeric, yeah.

So tell folks what that implies, because that's another wrinkle in the story. Well, that's the other thing that I think is, there's so many dogmas that we believe until data proves otherwise. So one of the warts of rituxen was thought that it was a chimera. It had too many mouse parts to human parts and that we would cause human anti-chimera antibody HACA. And FDA was very concerned about this.

So we measured and measured and measured. And it turned out probably because the patients had lymphoma that they didn't get HACA. Very tiny numbers and they're not clinically relevant. And you can treat them a lot. You can treat patients over and over again. Herceptin is 93% human, so not a chimera, but not fully humanized. And none of the patients treated with antibodies that I've seen, not with genetic or IDEC antibodies, have really had problems. They've had other problems based on target related problems,

not based on the antibody. And the CD20 antibody was just also a straight naked antibody? Straight naked antibody. And targeted for an immune destruction? It's targeted to destroy the CD20 positive cells. But it turns out that if you have lymphoma, you've got a reserve in your marrow of other CD20 cells of more immature that grow up and replace.

So it's not like you're really at a huge risk for untoward reactions from your CD20. And why do those patients with marrow that's still producing CD20 positive cells not go on in a constant state of lymphoma requiring? In other words, why is it that you can treat this and create a durable remission? I can guess. I don't know if anyone's done a formal study. I do think at some point in oncology treatment, if you have a tiny amount of disease left, especially something like lymphoma, you may take care of it yourself. So it's just getting rid of enough of the diseased B cells till you get the load down,

the tumor low enough that the immune system can wipe out the clone. And honestly, if it comes back, that's the other thing that I find really interesting about antibodies. The dogma with chemotherapy, if you are on Taxol and your tumor comes back, I wouldn't give you Taxol again.

If you're on Herceptin or Rituxan and your tumor comes back, in a heartbeat, I'd give it to you again. Yeah, it's a very different thing than chemotherapy. What was the price of these drugs at the time they came out? Were these the first chemotherapeutic agents, or you kind of want to distinguish them from traditional chemo,

but were these the first oncology drugs that came with big price tags? Probably they were. I think Taxol kind of went to that next level and then they went the further level compared to today's prices low. But Rituxan, I think more than Herceptin because people started using it more, like you'd use four times or eight times and recurring. Rituxan sales went very high, very fast.

And about this time, we get the whole anti-VEGF story, right? Yeah, yeah. That was. So Judah Folkman over at Boston Children's. At Boston Children's, yeah. Yeah, I never had the chance to meet him. Oh, you didn't meet him? I've never met Judah.

He wrote a fantastic book that I read in medical school, poured over the book. I'm blanking on the name of it. Do you remember the book? It was his story. Yeah, I don't remember. Again, a beautiful story. I'm smiling because I had a word for Judith Funkman talks,

which I heard many of. He was a phenomenologist. He would say, this patient had this, so it must mean that. He just connected dots all the time. I mean, some of it made no sense to me, but some of it was like, wow, I wish I thought of that. He was just a really fun person to listen to. I used to tell this story so many times. His thing was the cancer can't grow larger than a BB if it doesn't have new blood vessels. That was his thing. It stuck at a certain size. And so VEGF is

the primary way, vascular endothelial growth factor, is the primary way that you grow new blood vessels if you're a tumor cell. People went crazy about this hypothesis. It was more than the TPO that I was describing because it was due to Folkman and he's very compelling and very charismatic. And just because the hypothesis really- It's logical. It's logical. It's logical, it resonates, it sounds like a good thing. You know, the saying that I love is, it's the description of science as a beautiful,

compelling hypothesis slayed by an ugly fact. That's perfect. Yeah. Nappo Ferrara, also a great character, Italian OBGYN who came to Genentech and worked in one of the labs, made an antibody, actually same backbone as Herceptin, to VEGF. Mostly human. Mostly human.

Again, I think about 93, 94% human. And so we decided we should go after an antibody for VEGF as our next big oncology program. I still remember, by the way, one of the things that Gwen Fife, who's a great clinical oncology trials expert, was in charge of the program. And Gwen and I talked the day before the first patient was going to get treated with anti-VEGF. And Gwen said, my nightmare is that all the blood vessels fall apart. We've just put that into someone's body.

And I said, well, you know, we did all the tox studies. We're like, I don't think it's gonna be that bad, but we have no idea what, I mean, it just felt. And I'm sorry, this was before the first phase one patient? This was the first phase one patient. This was the first phase one. So you're going very low dose. We're gonna dose this late.

Very low. This is the first time it's going into a human. With the first human dosing of anti-VEGF, and we knew how important VEGF was. So we were scared. And this is also mid-90s. Yeah. Yeah. This is all happening when you arrive.

Yeah. It had just gotten there. I mean, what a time to be a Genentech. Yeah, it was wild. It was wild. Wow. So we're into the clinic, and we make progress, and it's really good news and lots of studies, and we're into the clinic and we make progress and it's really good news and lots of studies and we're ambitious.

We wanna do a lot of different, we wanted to do lung cancer and we wanted to do breast cancer and... How are you picking the cancer to study something like this? Herceptin's obvious, because you're targeting a receptor. Herceptin and Rituximab are easy. Yeah, they're easy, you know what you're doing.

But here, you could be targeting anything. There is one tumor where VEGF plays a seminal role, and that is renal cell carcinoma. And yet, renal cells are really tough to study. It's just not set up clinical trials-wise. Why is that? You've got the IL-2 stuff going on where you've got 10% of people will respond to it,

but 90% won't. Yeah, it should be easier. It may be the sites and where the clinicians are who care for it. It may just be that pragmatic. We kept struggling to figure out how to do a good renal cell study, but we thought we could do a breast cancer study, because we had a lot of networks of breast cancer patients,

and particularly patients who weren't eligible for Herceptin, because many of them weren't. So we wanted to do a late-stage breast cancer study because if we could help these patients, we would find out right away. These were patients with metastatic breast cancer? Metastatic breast cancer who had already tried everything. So really tough high bar.

And the standard you're going to hold yourself to in the phase two is 50% shrinkage? We wanted to have at least 50% shrinkage. We wanted to change time progression. This is a great time to actually hit pause. I wanted to do this later, but I think this is the right drug to go through two things. One, even though I've done this probably half a dozen times on the podcast, you should never assume somebody remembers it.

I want people to understand what the difference is between a phase one, a phase two, a phase three study. Also understand what's preclinical. It's not intuitive to people why it costs a billion dollars to get a drug to market and why it can take a decade. And then within that, if you could just embed enough of the details about decisions that you can make that will make or break you. How many times has a drug failed because the experimental design, the wrong patient selection,

the wrong disease selection, you have got to line up four pieces of Swiss cheese just right to get the pen through to hit it. Sorry to interrupt, but let's go back to, you got Judah Folkman talking about VEGF, VEGF, VEGF, that then turns into, well, if we made an antibody to VEGF, okay, so there's your idea. Now start the clock and start the dollars. So if you start with a target,

often in oncology today, we'll start with a target. There's twoology today we'll start with a target. There's two things you have to start with. One is what's the best way to turn down or turn off that target? Is it a small molecule? Is it an antibody? Tell folks the difference. How do you think of small molecule versus antibody? Where do we draw the line? So here's a really simple way I think of that helps me. Small molecules chemistry. Small molecule it can be not always a pill. A small molecule you're impacting on often pathways or enzymes or things that happen in the cell. A large molecule whether it's a protein or especially an antibody, an antibody's

biology. An antibody you're trying to do something that may be immune in nature, or you use the antibody as a delivery device. You're getting something to the cell. A company like Genentech and many modern companies really like antibodies. I like antibodies because when something happens, it's on target.

It doesn't tend to be off-target Small molecules that chemistry tends to have surprises in negative ways off-target like liver toxicity Kidney toxicity I do this through cardiovascular medicine to explain to people the difference between a Statin and a PCSK 9 inhibitor you have these two very common drugs that are used to lower cholesterol, but a statin is a small molecule. I don't say this in an insulting way, but we use the terminology, it's dirty. It does block an enzyme, but it's got all these off-target things. All this stuff. Yeah. Your liver function gets whacked. You get insulin resistance. Some people get horrible muscle

soreness. So, 5 to 10% of people taking this drug are gonna have a side effect that prevents them from taking the drug. I've never seen a person yet who couldn't tolerate a PCSK9 inhibitor where you inject an antibody into them that binds to a protein and shuts it off. That's really a good example. And the choice of molecule is driven by that. When I was first in product development,

there was this thing of, oh, you need a pill, especially for chronic indications. You need a pill for compliance. Right, who would take an injection for cholesterol? Look at obesity drugs. Turns out a lot of people would take an injection if they want to. But once you have your selection,

you need to make sure you can make it. And one of the critical things for a biotech company, if it's a protein or an antibody, is the small scale production of it, in small, they call it a mini firm. The mini firm has to resemble what is actually gonna be used, because the next thing you start doing is a bunch of models.

Judah Folkman giving a great talk doesn't mean you believe that blocking VEGF will help cancer. So we do models in mice, we may do larger animals. We do fewer animal models than we used to because they're really limited. I would rather have a great target with good biology than an animal model, but it's still helpful. It's still helpful.

And then the critical thing is the preclinical work that you do, what FDA is going to want to ask you, and they should, this is not them being bad, this is them being good, they're going to want to ask you about toxicology. What's your safety plan? Based on biology of edge-off, what are you most worried about? I'm most worried about bleeding. It's an antibody. I'm most worried about an allergy to the antibody. Did any of the tox studies show allergy to the antibody? What are you going to look for and how are you going to look? How often are you going to measure the patient? So the preclinical safety plan is really important and based on what you find in toxicology.

The other thing that's essential is, and especially modern oncology, if you have a targeted therapy, you must have a diagnostic. And that is wicked hard because you've got the therapeutic and the diagnostic at the same time. Now, things like CD20, things like VEGF are very ubiquitous, so it's not really targeted in the sense of HER2 where we needed a diagnostic. But if you need to have that, we had what we call the clinical trials assay for Herceptin that wasn't to be marketed.

Did you guys have to have somebody in parallel developing a CLIA certified assay that a pathologist was gonna use, or did you do that in-house? So we had an in-house clinical trials assay that we used all the way through phase three. And you could quality control the hell out of it? It was fine.

It was nothing wrong with it, except it wasn't approved. So not fine. So when we went to FDA, they said we're not approving Herceptin until you have an approved diagnostic. So whose responsibility is, like how do you encourage the world to make that happen?

So we went to Daco. We went to several diagnostic companies and Daco said, we'll make you a immunohistochemistry test for her too. And her sub-test is made by Daco. But we had to go back and correlate that with the clinical trials to make sure that it was the same as the clinical trials assay.

Now why didn't you guys do that in parallel? Was the cost too great, and did you wanna de-risk the drug before you sunk the cost into that? We were too inexperienced to realize we should have. I see. Okay. So nowadays we're doing that in parallel. Oh, for sure on parallel.

Yeah, for sure. It was a mistake. So how long, just to again, go back to helping people think through the arc of time, from the moment you guys hit a go decision on we want to do this, we want to pursue this path, how long until you file the IND? Oh gosh, it could be years. It could be two, three years because you're doing animal models. Maybe tell folks what the IND is so they understand why that's an important milestone. So the investigational new drug is asking the Food and Drug Administration permission

to ship an unapproved drug across state lines. If you and I wanted to do something in Austin, we could actually do it, which is sort of weird when you think about it, but most people don't really want to do that. So we're going to do the Peter Sue drug. It's going to be amazing. We're going to set the lab up right over there. But the moment we want to run a clinical trial- And ship it.

... and get it out of the state. You got to have the IND. So the investigational new drug is the request. And what happens is that you take all this information I've been talking about, that you know you have a molecule, you trust the way you're producing the molecule, you understand the biology enough, you have a safety plan, and you have a phase one protocol. So phase one has one purpose. We're all greedy.

I've been there. It is only for safety. Phase one is, is it safe to give humans this molecule? Is it safe to give it once? Is it safe to give it multiple times? And there's an art to knowing where to start the dose because it's an escalating dose trial. That's right. But you're extrapolating from what you learned about toxicity in a totally different organism that never translates one-to-one to the organism of choice.

It's absolutely true, and it's not uncommon, and you see people all the time backing up on the dose, thinking, oh, that was more than we needed or more than we wanted. But phase one, with a good pre-clinical package, a good IND, phase one should be uneventful. And because we are greedy in oncology, we always look to see if anybody responds,

just because that's what we do. But phase one often, to be fair, has some really tough patients who are trying something and have tried a lot of other things. So the patient population can be tough to find any efficacy in. So phase one, I always think of phase one as it might be a year that you're in phase one

if you're doing really good job. And typical cost given the relatively low numbers of patients. Oh gosh, in the tens of millions? Tens of millions, yeah. Yeah, tens of millions. And then you get into the 20s and 30s and 40s of millions with the phase two, depending on how big your phase two is.

And phase two, I think that's where people can use their intellect, I think that's where people can use their intellect, I think, in many ways. Phase two, you start to look at what's the right dose and schedule. Very, very important to get the right dose and schedule and... What's the right outcome? What's the right patient? Who do you want to treat? And really what phase two is supposed to do, with one exception, phase two is supposed to get you ready for phase three. You've got a dose, you've got a schedule,

you've got a patient selection criteria, and you've got a hypothesis of where this is gonna be a drug. The exception in oncology is sometimes you wanna get an approval off phase two. When we tested anti-VEGF in breast cancer in phase two, we wanted to use that as an approvable study. Because we would go in and say, look, it can be a contingent approval,

but these patients have nothing else to do. And so I think that can happen, especially targeted therapy, where you've got the perfect target and FDA's feeling good about it too, that can be a phase two study. But most of the time you're getting ready for phase three. So where were you guys with anti-VEGF in phase two? You were at breast cancer and did you do colon?

We did colon, but not the kind of study that I just mentioned for approval. We did a traditional phase two in colon. So what happened is the breast cancer study failed. And I was so disappointed. I was so hoping that that would work. I still remember that day. For me, it was like, oh, we need more better drugs for breast cancer because I often heard from people

when they're the three out of four patients, two-herceptin wasn't for them. If you looked at your stock that day, it also looked really bad because all the hype about Avastin was there. But in colon cancer, we had a phase two, got ready on the dose and schedule, and then we went to a phase three but in colon cancer, we had a phase two, got ready on the dose and schedule, and then we went to a phase three study in colon cancer, much more traditional, just plus minus of Aston. Five FU and the usual suspects. Five FU and the usual suspects, plus minus of Aston,

and that succeeded. That was a stage four? Only stage four. This is a median survival study. You're not doing overall survival, correct? That was a median survival study. Actually, I don't remember all the details of that one. I feel like it was eight more months of median survival study. You're not doing overall survival, correct? That was a median survival study. Actually, I don't remember all the details of that one. I feel like it was eight more months of median survival.

Does that sound about right? Probably right. It was the first new thing in colon cancer for a while too, so people were pretty excited. Now, at this point, I'm in medical school, just down the street. I'm at Stanford. And I remember we had a big discussion about this.

I'm in my first year of medical school. And the discussion we had in class was, I think at the time Avastin was $100,000 for the treatment. Extends median survival by whatever, but I think it was eight months. The UK said no. The NHS said, we are not paying for this because at the time the NHS had this $100,000 quality adjusted life year hurdle, which is understandable, right? That's how you throttle supply side economics. They said, look, we can't pay for a drug.

We can't pay more than $100,000 for an incremental year of quality adjusted life year. This is only giving you eight months. That's why I know it was less than 12. And so the NHS flatly said, we're not paying for this. And I do believe people in the UK could pay out of pocket for it. You can get it out of pocket,

but not through the National Health Service. That's right. People in Canada could not because you couldn't have private insurance in Canada, you could come to the US for treatment. So of course, this just became a great topic of discussion for med school freshmen. What was your thought at the time of have we moved the needle enough? How do we think about the economics of this? So I had a lot of different reactions. First of all, with Avastin, it was the first time I remember reading, and I think it was one of those curtain-raiser things in the Wall Street Journal for the breast cancer

study. The headline was, Avastin might help breast cancer patients, but can they afford to take it? I was shocked that it was the first time I had read, and as long as I had been at Genentech, that somebody couldn't afford one of our drugs. That instead of saying, oh, isn't that cool, rinoxan, herceptin, avastin, it was too much money.

And that felt really important to me and really not good. We had as a company a philosophy that no patient should go without any of our drugs because of an inability to pay. So we had a bunch of patient, what do you call those patient support programs or whatever, so we had a bunch of different things in place. So I knew we had those programs but that doesn't help the patients in the UK and it doesn't help the overall cost because we're actually supplementing but the cost is still really high. And we started to have a lot more discussion

at the executive committee about the price and how we would think about it and how we would price the drugs. Because that was, like I say, that was not good. Did you go straight from Genentech to being the chancellor at UCSF? Just because I want to stay with the story, I want to continue the arc of your career.

We're at the halfway point, right? We're one third of the way in theory. Early days. Yeah, yeah, yeah, career. We're at the halfway point, right? We're like we're one third of the way in early days Yeah, yeah, yeah, yeah, we're in the 90s How did you given you are truly on the cusp of what is happening in? oncology and biotechnology and now the same institution that said you can't come back here to have a clinical appointment after Saving the people of Uganda is now offering you the highest post essentially outside of a provost, I'm guessing, right? I don't even know where the chance-

It is the highest post. It is the highest post. Okay. So that's kind of remarkable. And does that just speak to what they saw as the vision of that institution, which was few people have learned what Sue has learned in the last 10 years and we want that type of leadership here.

So first of all, on the genetic side of things, Roche bought us. That's right. That was 99? That was 2009. Oh, 2009. Oh my God. Okay, I'm off by a whole decade. I thought that was sooner.

2009, which was not what we wanted. It was a- It's a hostile takeover. A hostile takeover, yeah. They call it in the business world a squeeze out. They squeezed us out. So I knew I was gonna leave. I knew I was gonna do something different. And UCSF, I had been really close

with the chief of medicine, who was my chief of medicine when I was an intern, Holly Smith. Do you know Holly Smith? No, I don't. So Holly Smith was a South Carolinian, Harvard-trained, amazing person. And between him and Bill Rudder, who founded Chiron, who's a biochemist, they decided a

long time ago that UCSF should not be a backwater medical school and should be a serious medical school. So Holly on the clinical front and Bill on the scientific front just decided they would start recruiting people to have a great institution, like a pretty amazing thing. And Matt was starting in the 80s? It was probably 80s, 70s, 80s. I was still friends with Holly. I just think there's so many wonderful things about Holly that I admired that I was still friends with him.

So Holly called me and said, Mike Bishop is stepping down. Of Bishop and Varmus, that's Bishop. Of Nobel fame. And you should be chancellor. Of course I said to Holly, I'm not a professor. And I said, well, if they're interested in me, I'd be open to talking to them.

They were, and I went through the interview process. I'm sure that when you're going through that, sorry to interrupt, because you're now interviewing with the Board of Trustees. They have a search committee. Yeah. Yeah. And so they must be asking you to present a vision. They're not interviewing you to make sure you know how to use PowerPoint.

Yeah. Do you remember what the vision is that you presented to them? What I do remember, and I remember, if you remember 2009, was just... Post-apocalypse. Horrible recession and California being particularly in a bad place. So I just talked to them about how I think about managing people, how I think about making sure that you use whatever assets you have maximally. I admitted that I had never done fundraising, but I had done a lot of work with Wall Street and I could talk. You were the president. What was your title at Genentech before you left?

President. Yeah. And I did a massive amount of investor relations because Art didn't like traveling or talking. So- My kind of guy. Mine too. No, we were a good partnership but I also said look if you think about running the faculty meeting I'm probably not your guy but that's what the provost does. I think they really thought they

wanted somebody who could work on the business aspects of the campus. We needed to finish mission. You're really the CEO of the system. Yeah yeah what you're doing. Yeah, yeah. And you manage the hospital CEO, and it's a big hospital system. There's no undergrads at UCSF. So that was what they were looking for, and I thought, well, why not? Were you nervous? I mean, when they called you and said you've got the job,

was there a moment where you thought, have I bit off more than I can chew? This is a huge responsibility. I was really concerned. I was really concerned. I was really concerned about it. And I also realized, because some of the faculty were pretty negative when I first started. Because you're an outsider, you were an alum,

but you weren't coming up through the ranks as the CEO of the hospital or something. I actually think they were just as nervous as I was about money. They weren't convinced that I knew how to get them money. Because if you're running a program, you need money. It's the mother's milk of doing science. So tell me about the budget of UCSF.

Because it's a state school, presumably California provides what fraction of it? Almost nothing. So what's the benefit of being a UC? The brand. There's a curriculum thing. There's some things like that. So in that sense, you and Stanford aren't that far apart.

Not that different. I mean, the most important things, you've got clinical income, you've got NIH-driven income, right? You've got other grant income, and you have philanthropy. Show me the P&L on those things there. So NIH is bringing in how much? Oh, gosh. Percentage-wise, roughly.

Of the money that you use every day, there's this discussion of overheads now. It probably gets up to a third. A third of the revenue for general operations is coming out of the NIH overhead. Probably, yeah. And then clinical revenue. Clinical is a lot, but a lot of it goes back to the hospital. You know, it's a not-for-profit, they spend it on the hospital. Okay.

And then philanthropy is some direct, some into the endowment where you're living off the interest. Okay, and then philanthropy is some direct, some into the endowment where you're living off the interest. Yeah. And that's basically what your revenue streams are, those four things. And then the tuition is tiny. Well, especially because you don't have undergrads, right?

Right, right, because the number of students is really low. And the really good news at UCSF. I didn't even apply to UCSF, by the way, because I mean, I was not in California when I was applying to medical school. I was told it was such a great medical school that I was like, there's no way I'm going to get in as a non-Californian. So I didn't even apply.

So the funny thing for me is- But you did and you got in. I did. Well, there's a story there. We talked about me being at University of Nevada. What we didn't talk about is my first year at University of Nevada, my youngest sister was born. So I lived at home and helped my mom in Reno. Because there's like seven of you, right?

There's seven of us. Yeah, and number seven was born when I was a freshman. It was kind of crazy, but when I went to medical school, I used to have like this sign on the stairs, be quiet, I'm studying down here. That's like probably a giant pain. But I wanted to go to San Francisco. My dad was born and raised in San Francisco.

My grandma lived in San Francisco. So even though I was still pretty young in terms of ever living outside the home, I knew San Francisco I wanted to go. But UCSF had never taken a University of Nevada student, because we were a pretty new medical school. I was only in the second four-year class. Oh, wow.

Yeah. And I was excited like my head would blow off. Like I wanted to go to UCSF so big time. So I'm going back to UCSF, and the really good news, what saved me as chancellor is philanthropy. It turns out that we needed people to care about the mission and the projects at UCSF right at the same time as the Mark Zuckerbergs of the world and the venture capitalists of the world and a lot of people had come into a lot of money. Even though the overall economy was bad,

it was coming back and we had some spectacular successes and my successor, Sam Hawgood, continues to have that kind of success and people are just really generous. Mission Bay. Americans are hands down the most generous people in the world. I think that's demonstrable fact. Yeah, I'm big on New Year's resolutions,

am I not the thing? One big on New Year's resolutions, among other things. One of my New Year's resolutions, I have a mini list. One thing that's always on the list is be more generous. I'm no Mark Zuckerberg, but I can be generous in other ways. I'm sure that you must deserve some of the credit for that. I don't think it's just that a bunch of people

in the Bay Area came into money at that period of time. What was the approach you took towards philanthropy and how did you reach donors that maybe previously hadn't been involved in UCSF? Because again, one of the things that's working against you is you don't have an undergraduate. So Stanford has a big advantage over you in which you've got a lot of people

that are coming through doing engineering degrees, doing CS degrees, who are going on to create enormous enterprises. Anyone who's an alum of UCSF went to graduate school there. There's no business school. There's no law school. So you're missing out on a lot of this. Don't forget the hospital. Yes.

The most important donor base is Grateful Patients. Yes. Or people who love science, technology. I hired John Ford, who had retired as the head of Stanford's fundraising, moved up to the Northeast, and he was my head of development. And I talked to John, and I said, how do you do this? Teach me how to be a good fundraiser. And he talked about, tell people your hopes and dreams.

Tell people what you're excited about, and ask them what they're excited about, and see if there's a match. And I think that was really important and then I also think that because I had been at Genentech and I was sort of gregarious and knew a lot of people and people knew that I had a decent business savvy, I wasn't gonna waste their money. We were very committed to use the money wisely especially in the hard times and do special things at UCSF. So I was surprised, I sort of worried that I would be sad

if people said no, that it would be weird, especially if I knew them well. So I would get myself psyched up for the beginning of it, and then by the end I would be like, oh, that's fine. Next time if you're in town, let's talk again, and maybe it'll change or whatever. But it was actually fun. I got to talk to and meet a lot of great people.

What percentage of your time was spent externally versus internally? Probably 40% externally, a lot external. And what was the internal focus then? Working with the team. So who were your direct reports? The provost? The provost, CEO of the hospital, lawyer, all the deans. That was really important.

And then part of it was monthly we met with all the chancellors, with the president of the university, it was Mark Udolph at the time, and then he stepped down after a while. But the chancellors' meetings were funny because they all had undergrads. And so I always felt like I was squirming, like, are we done yet? I thought it was just really important. because they all had undergrads. So I always felt like I was squirming, like, are we done yet? I thought it was just really important. My favorite thing, every Friday, lunch, Mission Bay, they had a science talk.

And they'd have some pizza, Chinese food, something, and you'd look around the room and it'd be like Bruce Alberts, Liz Blackburn. There'd be four Nobel Prize winners in this little cramped room listening to science. This would be something you did as a scientist, not necessarily as the chancellor. Not as the chancellor. The chancellors weren't doing this all the time. No, I'd just go over on the shuttle bus,

eat a slice of pizza, and enjoy. Yeah, amazing. It was really good. So then let's get to the next chapter. What, all of a sudden, in 2013, 2014, leads to the next transition to being the CEO of the Bill and Melinda Gates Foundation? Well, to my surprise, I think I got an email or I think it was an email from Melinda. Did I have time to talk? And UCSF throws a big event every year that's kind of friend making, fundraising, everything, and we give out awards,

recognition to people whose work we respect a lot. So I had invited Melinda the year before and thought she'll never come. You invite people, the throwaway invite. And she accepted and came, actually came with her mom and dad even better. And I thought that was nice. So she sent me an email and she said that she and Bill

wanted me to look at being the next CEO of the Gates Foundation. And I was surprised, I had not expected that. And I started having discussions with them. It was actually funny. I went up to Seattle and they were having all this hush hush. You know, this was very cloak and dagger. So I went to their house,

because I had had a meeting with Melinda and I needed to meet with Bill, and it was Halloween. The kids are coming and going. It was kind of crazy. And so I had talked to him and I talked to my husband. You know, my husband worked at the Gates Foundation. He led the HIV and TB programs about five years before. Was he still there?

No, no, he had gone. He was commuting to Seattle, which was dreadful. But he knew the Gates Foundation, so he and I were talking about this, and I was like, oh, God, you know, I've only been at UCSF five years, and I just found where the bathrooms are, you know, that kind of thing.

And it was going well, I was happy with that. They asked for a teleconference and they got on the phone. And especially Bill made this big pitch that a lot of people could do the UCSF job, with all due respect, as Bill would put it. But I was the only person who they both wanted and who could do this job. I was perfect for the job,

and it's really important for the world, and I needed to do it. I assume that the rationale for that was obviously their focus is on global health. Global health, yeah. And you have the background in the clinical side, the research side, the epidemiologic side, the management side. So there's kind of those are four legs of a chair. Were there other things that I'm missing that they felt were kind of those are four legs of a chair. Were there other things that I'm missing that they felt were kind of essential pillars?

I think it was less obvious then, but I think now they had started to kind of have disparate views of how the foundation should operate. Melinda has been really all over women's issues, all over. And Bill would do another run at polio. It's like the goal broadly that all lives have equal value, which by the way I think is a wonderful thing,

they share but they come at it from different ways. And so I think that the thing that resonated for me is that I could see both those points of view. But those points of view don't strike me as mutually exclusive for an organization with enormous resources. Yes and no. It's one thing to have enormous resources, it's another to know where one of the most

important assets they have is the time and energy of Bill and Melinda. They actually show up, things happen. So how did you weigh this decision? I thought that I could add value. I thought I would learn a lot. And I did think that UCSF would be fine without me. I felt like we were back on our feet financially. I thought that Sam Hawgood, who was

the dean of the School of Medicine, I had a ton of respect for him and thought he was the obvious person to take my place and that it would be OK. Were they surprised? Did they try to talk you out of this? I don't think they did. I actually think they had a lot of respect

for the Gates Foundation and thought, oh, well, that's a cool job. At least the way they showed up with me. Maybe when I wasn't there, they did. Okay, so you head up to Seattle now. Yes. When you show up to the foundation, how many employees are there?

What does it look like? It's a not-for-profit, but does it run like Microsoft? I mean, how does it operate? It's a couple thousand? It's a not-for-profit, but does it run like Microsoft? I mean, how does it operate? It's a couple thousand. It's a big foundation, big building, big foundation with people all over the world now. There was a lot I wasn't surprised by, like the global health stuff. I knew what they were doing and I thought it was interesting and great. And the challenge for me was Bill's endless appetite for things like learning things, driving things, funding things, and me feeling like I could get my hands around a strategic plan. It was

a little bit like, okay, the staff would be like, Bill's gonna love this. Let's present the, you know, it was that kind of feeling and lots of money. So I kept trying to get my hands around like, okay, what should we do so it's just a little more orderly and we get a great return on our investment. That was the most important focus. I feel good about that. The funny thing was I sent the finance team to Genentech and we had this really great portfolio management process

that we put in place when I was there and they still use it apparently. And we had this really great portfolio management process that we put in place when I was there, and they still use it apparently. And because I recommended to Bill, we just have a portfolio management process. Pretty simple. Everybody knows how you make decisions, what money's up, what we'll do, and we can use that here. Doesn't need to be bureaucratic. Bill said, we don't need it. It's all in my head. I remember that conversation. And I thought, if it wasn't you, I would think that was a smart-ass thing to say. But I actually think you're just being honest. So I encouraged him to understand that just because it was in his head didn't mean that

the rest of us were there. We had a little more ability to make things orderly, I'd say. It was a wild ride. It was six years of a wild ride. What was the most difficult thing for you to impact that you wanted to change? Meaning, was there a global initiative that you wanted to get your hands around that you just couldn't do organizationally or technically or what were the challenges? I would say far the opposite. The things that I felt like I knew about, I felt like really good about.

The TV stuff, there's a HIV cure program now that I'm really psyched about. Technically, I felt really good. Probably the hardest thing for me was the people side of things. I have a very strong sense of how people should treat each other and the competencies that managers should have.

And I'm not willing to move on that because you're a technical expert. And I found that if you do move on that, it just changes the culture. And I struggle with that. Say a little bit more on that. Is that because in the not-for-profit space, you have a different talent pool than you do at Genentech? No, I think it's because Bill really likes technical experts. And if he likes the technical expert, he doesn't want his CEO to come and say anything.

But yes, they are very smart. What did the org chart look like? So I assume Bill and Melinda are co-chairs. They were, yeah. And then as the CEO, who are your direct reports? Is it organized by a bunch of GMs in different programs? Yeah. So there's a TB person, an HIV person, a polio person, a malaria person?

Global health person, there's a global development person, there's an ag person. So under global health, you then have sub? Then you have the subs, yeah. Global health is a big job, obviously. It's a very big job. That's the biggest. Yeah, it's the biggest P&L. And then US education is a pretty big job too. I don't even realize, I'm not as familiar with the portfolio.

Yeah. The one that has been Ag is now Ag Financial Services for the Poor. So it's a pretty broad group. What's the annual budget? Eight billion. Wow. So it's a pretty broad group. What's the annual budget? Eight billion. Wow. So much money. It's amazing.

Yeah. So what are things that you could not have done there in that role had you not had the leadership roles at Genentech and UCSF? Oh, gosh. I think more the people side of things. I remember there was an employee who was really struggling at Genentech and her boss, I was his boss, and he kept talking to me about how she was struggling, how she was struggling, could we do this?

Do we need to give her fewer reports, more reports, make her job harder, make her job easier? Like we couldn't figure it out, couldn't figure it out. Performance was struggling, you mean? Performance was struggling and just not acting like she had been, we just couldn't figure it out. Couldn't figure it out. Performance was struggling you mean? Performance was struggling and just not acting like she had been. We just couldn't figure it out. And finally one day she said oh I'm getting a divorce and after a little while things got better and I thought you know not everything's work. Not everything's work. So I think as a manager I really care about people thriving at work. I really care about it.

And when I went to Gates Foundation, I think I understood better given Genentech and UCSF that a very important principle, work never fills in for home, ever. It never makes up for bad home. So if somebody needs a timeout, I always think how can I improve work? And sometimes it's good to just

understand that that's not always the case. Especially if you're working in global health or global development, you might be in South Africa, you might be in China. It's rough. So just thinking a little bit about how people can show up in ways, it's $8 billion. How do they maximize the benefit of that $8 billion? And what can I do to enable that? Are you basically only able to affect that through your interaction with your direct reports and just hope that that's the infusion of culture that

then trickles down? Because it's hard to go two levels below your management. And yet, the people who probably need this compassion the most are people you're not even going to meet. Yes and no. One thing about traveling a lot, you have big events or things like that is you meet people on trips, and that's different people throughout the organization. So I think there are opportunities.

I also set up meetings when people would have a grant that needed to be signed. The business process was it would show up on my computer. So I changed the business process so I got the group that could fit around the table in my office and we would talk about the grant so I could interact with more people that weren't my reports, which I really liked. So I do think it is mostly through your reports, but I think there are ways that at a senior level you can interact with people culture-wise. Yeah. The word culture, it's very misunderstood. When you think about the culture that you

wanted to bring to the Gates Foundation, I'd like to understand what that was and how successful you think you were able to be. And I say that because you were in an organization where you also had very powerful other present people whose culture was also a part of the organization. So for me, I define culture in a really specific way that when you come to work, you feel like the atmosphere, the surround sound brings out the best in you and that you have some ownership of tweaking it if it doesn't. So that's something that you feel like you can control.

Because if you're in thousands of people or hundreds, thousands, tens of thousands of people and you're the CEO, you're not going to do that. But that you set up that culture. One of my favorite stories from Genentech was being at a product development meeting that my successor as medical officer Hal Barron was running. And Art and I both attended just because we loved it and we wanted to be there, but we weren't decision-makers. We were just attendees.

Which is kind of odd. The person who's the decision-maker is sitting in the presence of the two most senior people in the company leaving it to him to make the decision. Yeah. But in this case, there was someone who, the discussion was about her septum and how well the test to find who was her two positive performed.

And if you got more patients, you would get more commercial, but you would have patients who wouldn't benefit. And someone who I won't name said, but if we have a test that does like this, we can get more money. And as if in unison, Art and I both rose up from our chairs and said, we never do that. We don't do that here.

Done. Everyone kind of sat down and we weren't the decision makers. But see, that's culture. If you wondered, it's right where the decisions are being made and everything else. That for me is culture. The other one that because I'm in so many meetings and was in so many meetings at Gates Foundation, I had a practice. I would sit, Bill would be there or Melinda would be there, but often Bill and me

there and you're presenting. And Bill's peppering you with questions, some of them very tough, in a very tough way. I would look at you, you got this. I can't tell you how many people, I actually didn't even know I did it, that I would nod. You were the coach. Smile, coach. I would also stall. Hey, hold on a minute, Bill. I think he's just getting ready to answer that question. You're talking over him right now. In a nice way, not confrontational. That for me is culture. I want you to succeed. I want you to know I want you to succeed. It's the guy who runs the foundation. It's

the two people who are the chairs. So it's gonna be scary. That's why I think that bringing out the best in people and giving people agency to do that on their own means that if somebody sees Art Levinson say, that's not the way we do it here, they'll go down the hall in a different meeting and say, you know, I heard Art say, I think that's really powerful. That's really powerful. So this brings us up to 2020. And were you at the foundation when Covid hit? I had announced that I was leaving and literally packed in the house as COVID hit.

Actually a few miles from us, the first case in Washington State, nursing home. Yeah, interesting. Let's talk a little bit about COVID. So I've talked before about this idea of the difference between science and advocacy, and I still haven't really wrapped my mind fully around it other than kind of a sense of lost opportunity with COVID. What do I mean by that? Well, on the one level, there was so many pretty incredible things that happened with respect to the speed with which a vaccine could be developed that really made a difference in terms of mortality for a subset of the population.

But a lot of that's overshadowed today by the lingering doubts, the lingering suspicions, the mistakes that were frankly made. And my fear is I'm not convinced we're better off today in terms of preparedness for a pandemic than we were in 2019, which seems like an unimaginable statement, given what we've been through. Do you think I'm too pessimistic? How do you feel? AMT – I do not think you're too pessimistic. I am absolutely horrified.

Horrified. It's shocking to me that the narrative is in the place it is today. And I'm honestly still processing how we got here from there. It is a really bad place. And I think you're right. I think if it happened again today, it would be the way it was with worst of COVID, but even worse.

Because trust and the need to have sides and winning and losing, I don't remember health and medicine being winning and losing and sides as I've been in this business for 40 years. It's just weird. I don't get it. Yep. I concur with all of that. And I do wonder what it will take to restore confidence.

Look, we could sit here and talk about mistakes. It might be that the medical community and the scientific community need to be more vocal about acknowledging mistakes. And I do think an enormous mistake, though it's understandable to me why it happened, because so much was happening so fast. But I believe deep down it was an enormous mistake

to be the head of science, to be the head of advocacy. I think having Dr. Fauci as being both of those hats was a cataclysmic error and it's not about him. No human can do that. A scientist has to be an impartial observer of fact who is happy to change his or her mind in the presence of new information with no attachment to what has been said in the past. An advocate has to be driving policy and action. And sometimes they have to settle for the best you can do any port in a storm. When you put those two hats on the same people, I worry that you lose all trust. I do wish the medical community could have an open and honest discussion about that.

I would say that not if, but when, we will have another pandemic. There's zero doubt in my mind. Bird flu is working hard on it right now. Yeah. We will absolutely have another pandemic. I hope it is decades from now, but we will. I hope somebody will remember that lesson and say, we want our chief communicator of the state of the science to be completely uninvolved in telling the public what to do, simply there to report what we know today.

Today, we think masks work. You know what? We just did a study and we realized they don't work worth a lick. Today we believe vaccines prevent transmission. We just did a follow-up survey. They don't prevent transmission. It's okay. It's okay. I think that's a very forgivable position. I think the public would welcome... Look, I just told you about bone marrow transplants for breast cancer. If you tell people, look, here's what we thought, we thought harder

treatment was better for people, it's now proven that it's not. Science changes, people know that, but you're right. I think that being honest and open when it changes and how it changes matters a lot. It really does. I also think you didn't say, but I would add to your recommendation, which I think is a really smart one, the pace of communication, the social media and misinformation or just stuff gets out there really fast. And having something slow doesn't keep up. I don't have a solution to that.

I mean, the great example, which is a very good example, and I don't have a solution to that. I mean, the great example, which is a very good example, and I don't know the solution is in May of 2020, if you suggested that this came out of the Wuhan lab, I mean, you were kicked off social media, you were kicked off YouTube, you were in the doghouse. That was misinformation. Well, I think almost any observer today would agree that that was actually information. But where do you draw the line? I don't have an insight. This is so far above my pay grade. Yeah. I don't think it's a matter of kicking people off because actually I think you enhance that and you may be wrong, but being part of the dialogue. I'll give you an example that I've been reading the last couple of weeks. Ivermectin for cancer.

Actually, I'm glad you brought that up. I wanted to have a discussion about this. Okay, finish your point, and then I want to make a broader point about oncology. So my point's a simple one. The nature of whore is a vacuum. So if you say I'm not gonna kick off people, the lab is a good example,

but I'm not gonna remain silent. Here's what I know about that thing, about the lab. Here's the facts, here's the publication. You know, I think that the absence seeds that space to people. I feel like the anti-vax, specifically things like autism, many people have seeded that space on social media because you are kicked in the butt if you don't.

So I do think you can't leave a vacuum. Yeah, I think that's a great point. I'm glad you brought the ivermectin and cancer thing up. So a couple of my patients, which is a statement, I'm going to acknowledge that my patients are educated and affluent people for the most part. A couple of my patients have sent me clips of various people claiming that Ivermectin is curing people with stage four cancer. Now, because they're sending these to me in text and I'm really, really busy, I'm responding in a rather glib way, which is usually using phrases like,

this is effing bullshit. But I usually follow it up a few minutes later with a text that says happy to discuss. And usually they say, no, Peter, I just needed to know that this was nonsense. But I also agree that I don't think people should just be taking thing on faith. And I really want to be able to offer. So I think I made a note that actually I wanted to discuss this exact example. And hopefully we'll be able to clip this particular segment so people understand why this is such a idiotic statement.

To believe that ivermectin cures cancer and to listen to the stories of multiple people with all sorts of different metastatic cancers that are cured, you're almost explaining that cancer is a single disease. So explain why at face value the idea that anything could cure multiple forms of cancer is an impossibility.

It is an impossibility. There's no doubt about it. Every cancer has very specific biologies that allow it to grow and spread and cause humans problems. And that's why you don't go to the cancer doctor. You go for a prostate cancer, You go for a gastric cancer. You go because the biology of each of the cancers is different.

And when you go even one step further, as you've alluded to, it's not just that colon cancer and breast cancer are as different as kidney disease and heart disease. It's that breast cancer with an estrogen receptor that lights up versus a HER2NU receptor that lights up versus no receptors that lights up, those pretty much have nothing in common

other than the fact that they originated from the mammary cell of a woman's breast. Right, so we use anatomy to describe where the tumors are, but it is not irrational to use different doses of medicines in combination with other doses. The thing that we went over is the preclinical phase one, phase two, phase three is meant to give whatever cancer patient, whether let's, in this case, I think prostate cancer has been talked about a lot, all the information they deserve on both safety and efficacy.

Does it work? Does it shrink the tumor? Does it help them live longer? I haven't read anything about ivermectin doing that in patients and what the side effects are and how it could harm patients. So I think patients deserve that kind of information. The other issue I have with this type of rhetoric is the next line that follows is the pharma

companies all know this works and the reason they're keeping it from you is so that they can make more money giving ineffective drugs. Now again, I'm going to offer my point of view on this, but you being the veteran of some of the biggest pharma companies in the world, feel free to correct me. I think pharma would be happy to have a drug like ivermectin that cured all cancer because the first thing they would do is put a slightly different modification to it to make it more efficacious, basically less side effects, and they would patent it and they would make all the money in the world.

They'd be all over this. If they're able to make $100,000 on a drug that extends your life by eight months, I promise you they will be making millions per drug if it's curative. So again, such illogical arguments are put forth and it drives me sort of bananas. But if we want to go back and say, how did we get here? I think when my friend Joe Rogan took ivermectin for COVID, which when Joe asked me, what do I think? I said, Joe, I think it's a totally safe drug.

I'm pretty sure it has nothing to do with why you're feeling better today. I think you're feeling better today because you have an amazing immune system. You're an insanely healthy human being. You did 10 other things, two of which might have worked. I'm pretty sure the ivermectin had nothing to do with it. That said, the medical community didn't say that to him. What they said is you're taking horse dewormer, you idiot. Well, that was a strategic error. That's an awful way to talk to somebody. Ivermectin might be a horse dewormer, it also happens to be, and I look this up Sue, there is no drug on planet

Earth that has been taken by more human beings than ivermectin. And it might have the fewest side effects of any drug out there. And look, there may be human conditions for which ivermectin helps. Works beyond, yeah, exactly. Beyond what we know. And I think that's an opportunity for somebody to study it. Good for them. But again, it's something about the elitist nature in which that was handled that has now created this terminal effect of ivermectin is a cause celeb for, I mean, pretty soon someone's going to say it cures Alzheimer's disease, I'm sure.

Well, I think it's a drug that's an anti-smarty pants drug. Yeah, that's a great way to put it. That's what it is. To me, that's heartbreaking. Becausesmarty pants drug. Yeah, that's a great way to put it. That's what it is. To me, that's heartbreaking. Because the answer should have been, I talked about this with Joe very openly on his podcast. I said, look, I've looked at all the RCTs of ivermectin and COVID.

There's no signal, except my memory could be off on this. But there's a little signal in this Brazilian trial. But the methodology of that trial was horrible. So I have to believe this is not working. It's a good try. All about trying. It was a great idea to take off-the-shelf drugs and see if they worked. AMT. NIEPORENTURA Nothing wrong with that. We've done that for other things. S.D. When they don't, we have to move on. By demonizing it and by demonizing the people

that felt it might work, we find ourselves in a situation right now where it's very irrational. AMT. NIEPORENTURA One of the things that I did over the last four years is participate in the President's Council of Advisors on Science and Technology and co-chaired a report on the future of public health. And we ended up thinking that we're focusing on the workforce. One of the remedies for the issue you and I just talked about is having a broader set of people who we think of as the public health workforce. And I think people who are interested in ivermectin, farmers, people who are up close and personal to some of the things with this bird flu, there are a number of different folks who

would be really interesting to involve in public health efforts, and we typically don't. And so I think that's one of the ways that we can go forward in public health is to think about how do we define public health and what does it look like? Yeah, I agree with that. Public health has really struggled in some ways. You've had these incredible success stories

and then some awful failures. On the surface, it's such a great thing. I think that's why Make America Healthy again resonates for people. People universally want- Yeah, how could you disagree with that? Want to be healthy. They want their families to be healthy.

This is a universal thing. And how to capture that and make that real, not ivory tower, but real for people who just want their families to have a chance at being healthy. I think that's a real positive. Yeah. I wanna talk a little bit about AI.

A lot of people might not realize you're on the board of OpenAI, and you're the only person in medicine on that board. So talk to me a little bit about how that came about. I don't wanna obviously talk about the implications of that, what you're excited about and what you're afraid of. So I joined the OpenAI board almost a year ago now, when they had had in November of 2023,

what they call the blip, which is CEO fired, board changed over. And I have been so impressed by the intellect, the commitment, the sense of responsibility of folks at OpenAI. I hope this is maybe a little crazy, but here's what I hope. If I had a top two things for AI, one is in some of the things we've been talking about in product development. I mean talking about in product development. I mean, I love product development.

I think it is the best job on earth. You get to make new medicines for people who are sick. You go home and tell your mom and dad that they're happy. So what if we could take the tool of AI and make easy the things we can make easy? So you don't use AI to change a clinical trial. I still wanna know, does your tumor shrink? Do you feel better?

Do you have side effects? But there's a lot of study reports. There's toxicology reports. There are a lot of things that are labor and paperwork that are actually very important to establishing the safety, especially, but also the efficacy of a drug. I think using AI more and more on pieces of the clinical trials process,

so that if something takes time, it's because it's benefiting a human, not because we just couldn't do it fast enough. So the clinical trials, I think, still has some opportunities for that. Give me a time and money sense in terms of savings. This is a very important question. If you said the entire clinical trials program for a drug is six years, let's just make that

up. IND to approval. IND to approval. I would want to cut it down by two years. And you believe AI can do that right now? Or we're on the path to that? I think we could be on a path to that. Now, the challenge of it is gonna be, if you say this example I like to give,

because it makes sense for people, if I'm changing five-year survival, if this is sort of a mature established thing, I gotta wait five years. I can estimate things and I can work with FDA to make sure if people can benefit. And you could argue with a regulatory change in the FDA, if we said greater emphasis on safety to approval,

greater emphasis on post-market surveillance for efficacy, we shift this thing a little bit. Now you could say at three years we're trending, you get a provisional approval, and now we're going to follow you. There's an example, like Paxlivet in my mind, you could argue maybe should have been pulled, maybe wasn't as effective as it looked in the trials,

and that doesn't mean they were wrong to approve it, because it was any port in a storm. But after the fact, we could have been, oh, you know what, no harm, no foul, it was safe. You can always do that. And so maybe we do that for oncology. I think that the other thing is, you and I both know if you have 500 patients in a trial

and you look at safety, that's so limited. If you have a much more AI driven, why don't we follow safety in every patient on the dark? Exactly, ongoing. Ongoing. So I think the opportunities in clinical trials are massive. The other thing I would love to see is a change in the things that cause burnout of nurses and physicians and others in the hospital. This is across the board, not just in clinical trials.

Not in clinical trials. This is healthcare. Yeah. Healthcare should have tools where it's easier to decrease the load, the burden on both caregivers and families. I think that should be doable. It's not that hard. I think that should be doable. It's not that hard. I think that that is absolutely correct.

On the nursing front, there's a huge demand, obviously. How much of this do you think of absent robotics? So robots can really change the game. I'm not close enough to that, are you? I'm not close enough to the robotics piece of it, no. Yeah, so I don't know how long until a robot is doing what a nurse is doing. But when you think of medical and chart reconciliation

and things like that, is that where you think the greatest opportunity is? I think it is when you're trying to connect all the dots. That's the thing. What AI does so brilliantly is it just takes a lot of data and it comes out with observations. And if there are ways that that can assist at the bedside, that's a massive improvement, especially when people are changing, even me, University of Washington to UCSF.

It's so hard to change caregivers, to change health systems. Those kinds of things can decrease workloads. But I also think it's the kinds of things where clinical observations could be AI driven. So the Nobel Prize last year was awarded for protein folding, AI driven analysis. Explain to people why that is significant. How much do you think that particular achievement is going to advance biotechnology and what remains ahead of it as far as even greater molecule selection? These guys, what they did is they made possible, and we talked about preclinical, this is pre-preclinical.

This is how you even- This is figuring out what you're gonna do. Just figuring out what you're gonna do. If you can make figuring out what you're gonna do much, much faster, which they did, you're gonna have the opportunity. The way I think of it is you've got like a mountain of opportunity, but it's shown a light on just a limited number of things

where you can see the opportunity and take advantage of the opportunity. I think it's a start, but I think it's great that they were recognized. Do you think this is the most important thing from a promise perspective that AI is brought to medicine since? So far, yeah. Yeah, I do.

So far. And so what do you think would be the next mega unlock? Would it be on the data front? Would it be a predictive model? How could we shorten a clinical trial by 60%? Anything where AI can help us with outcome measures. I told you that my husband's an HIV doc. When we were both at Bristol Myers Squibb,

I was doing two by two measurements of tumors on x-rays for Taxol, and he was looking at viral load. Viral load allowed us to have 20 HIV drugs in like five years. It was crazy how good it was. I want a viral load for everything. You need a good biomarker. We need a good biomarker for more things. And you were talking about all the different types of breast cancer. So think about what you just talked about with breast cancer that you have ER positive, ER negative, HER2 positive, triple negative, there's all these. What if actually there's 15? Yeah, there undoubtedly are.

We know there are. There probably are. So then you're in 15 trials, but you only need 10 patients in each trial because it's so obvious you have the perfect remedy for each of those patients. I always think of it as, switch is on, turn it off, and you see clinical benefit. Anything we do that sets up like that,

especially if we can not just measure switch on, but switch off. That's why viral load is so powerful. Sue, what's your level of optimism or pessimism around liquid biopsies, and do you think that AI can help us with these? I have been pretty negative based on the data. I just have not seen the data that suggests to me

that we're helping. And is this on the sensitivity front? Yeah. Yeah. So can AI help us? Possibly. The problem is just really hard. Yeah, I was about to say, do you think the problem is tumors don't shed enough DNA?

I think that appears to be the problem, because if they did, I think it would work. So that's the most important problem. The other problem is something that I think we all tend to underestimate, because I love the concept of prevention. And I think Make America Healthy Again, in part, is we'll go to preventive therapy and stop all these.

And I understand that in oncology we've often celebrated tiny successes, but you can't have big successes before you have tiny successes. I don't think it's easy to do early detection. The only two things that are, well, now three, colonoscopy works. For cervical cancer, a pap smear works. Even better, HPV vaccine is my add. And now you can do a spiral CT for lung cancer. I'm not even using one handful of fingers, and we've been trying to do early detection as long as I've been an oncologist.

I agree with you, by the way. I would add to that PSA in the hands of someone who understands what to do with it. So PSA by itself, pretty bad. PSA density when you know prostate volume and PSA velocity when you have serial measurements starts to become very predictive. So you take a man who has not had a prostate biopsy and you stratify his PSA according to PSA density, the ability to predict if he has a Gleason 3 plus 3 or 3 plus 4 or 4

plus 3 is really quite high. It's high. At least you can then stratify those patients more quickly into a PHI or a 4K and ultimately decide do they need a multi-parametric MRI and you go down that path. It's not turnkey and I completely understand why they've said we're going to make no recommendation. I do take comfort in knowing, it's sad to me, but I take comfort in knowing too many men are dying of prostate cancer. It should not be the third leading cause of cancer death And yet I understand that it's a big ask to get every doctor fully up to speed on the algorithm You know what you just said that's something that if someone wanted to start a company

They could simplify that and make something more turnkey If someone wanted to start a company, they could simplify that and make something more turnkey for patients and physicians. When you go through the four leading causes of cancer death, two of them don't need to be on the list. Colon cancer and prostate cancer don't need to be on the list. They shouldn't be on the list. Now lung, I think we can reduce it a lot,

but it's going to be awfully tough. And breast is still really tough, because it's not health-steady. It doesn't have that straightforward progression from polyp to cancer. No, it's true. That's the neat thing is you can just take out the polyp. That's always been the beauty of colonoscopy. What is your level of optimism that we could ever... So instead of just talking about a

broad liquid biopsy, let's just talk about breast cancer. What do you think it would take? And do you think it would be a protein? Do you think it would be DNA? Do you think it would be RNA? If you had to guess what would be the earliest signature in the blood of different breast cancers, where would you put your money? I think it'd be interesting to look at protein. Think about how that would change breast cancer treatment. It would be tremendous.

It's funny, I say the following, deliberately not acknowledging your gender, because I'm sure you hear all the time, Sue, you are the most remarkable example of a woman in medicine. Gender aside, you are just a remarkable inspiration, period, as a physician, as a business leader, as a public health official. I have been a fan of yours for so long. When I walked into that room last year and saw you sitting there, I was giddy. So thank you for humoring me and making the trip.

Well, it was fun. I'm delighted to talk with you. Really enjoyed it. Thank you for listening to this week's episode of The Drive. Head over to PeterAtiomd.com forward slash show notes if you want to dig deeper into this episode. You can also find me on YouTube, Instagram, and Twitter, all with the handle peteratiamd. You can also leave us a review on Apple podcasts or whatever podcast player you use. This podcast is for general informational purposes only

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