Dr. Susan Desmond-Hellmann on a Career in Medicine, Oncology, Biotech, and Global Health

This episode of The Drive Podcast, hosted by Dr. Peter Attia, features an in-depth conversation with Dr. Susan Desmond-Hellmann, a physician board-certified in internal medicine and medical oncology. Dr. Desmond-Hellmann shares insights from her extraordinary career, which has included pivotal roles in academic medicine, the pharmaceutical industry where she helped develop groundbreaking drugs like Taxol, Herceptin, and Avastin, leadership as Chancellor of UCSF, and as CEO of the Bill & Melinda Gates Foundation. The discussion explores her experiences from the front lines of the early AIDS crisis to the cutting edge of cancer drug development and global health initiatives, culminating in her perspectives on the future of medicine, including the role of AI. This episode is particularly relevant for those interested in medical innovation, healthcare leadership, oncology, the history of modern medicine, and the challenges and opportunities in global public health.

Key Insights

• Dr. Desmond-Hellmann’s early medical career was profoundly shaped by her residency at UCSF during the dawn of the AIDS epidemic in the 1980s. This experience instilled in her crucial lessons on managing uncertainty, the importance of compassion in the face of overwhelming disease, and the urgent need for scientific breakthroughs.
• Her work in Uganda highlighted the devastating impact of HIV/AIDS in resource-limited settings and underscored the critical link between epidemiology, patient care, and public health policy. She emphasized how direct observation and data collection on the ground were vital to understanding and combating the heterosexual transmission of HIV.
• Transitioning to the biotech industry, Dr. Desmond-Hellmann played a key role in the development of transformative cancer drugs like Taxol, Herceptin, Rituxan, and Avastin. She detailed the scientific rigor, challenges, and serendipity involved in bringing these precision medicines from concept to patient, revolutionizing cancer treatment.
• Leadership roles at UCSF and the Bill & Melinda Gates Foundation provided Dr. Desmond-Hellmann with unique perspectives on driving innovation in academic medicine and global health. She stressed the importance of strategic planning, fostering a supportive culture, and the power of philanthropy in advancing scientific progress and addressing health disparities.
• Reflecting on the COVID-19 pandemic, Dr. Desmond-Hellmann expressed deep concern over the erosion of public trust in science and the politicization of health. She advocates for clear separation between scientific reporting and policy advocacy, and for more open, honest communication about the evolving nature of scientific understanding.
• Looking forward, Dr. Desmond-Hellmann is optimistic about the potential of Artificial Intelligence (AI) to transform healthcare, particularly in streamlining drug development, improving diagnostic accuracy, and reducing administrative burdens on healthcare professionals. She highlighted AI's role in areas like protein folding and biomarker discovery as crucial for future medical advancements.
• Throughout her career, Dr. Desmond-Hellmann has emphasized a patient-centered approach, the power of combining scientific rigor with compassion, and the importance of perseverance and adaptability in navigating complex challenges in medicine and public health.

Early Medical Career and the AIDS Crisis

Dr. Susan Desmond-Hellmann began her medical journey in Reno, Nevada, attending medical school there before securing her dream internal medicine residency at UCSF in 1982. This period coincided with the emergence of the AIDS epidemic in San Francisco. She described the profound uncertainty surrounding the illness; in 1982, it was known that something was affecting gay men, hemophiliacs, and Haitians (the "three Hs"), but the cause and transmission routes were still mysterious. Healthcare workers, including Dr. Desmond-Hellmann, participated in studies to see if they had contracted the unknown illness from patients.

Patients typically presented with Pneumocystis carinii pneumonia (PCP), an opportunistic infection rarely seen before, and Kaposi's sarcoma (KS), a distinctive purple-colored tumor that was externally visible and internally devastating. Dr. Desmond-Hellmann noted the tragic visibility of KS, combined with cachexia (wasting), meant patients "wore" their diagnosis. She recalled the initial stringent precautions, likening entering a patient's room to preparing for an operating room, with gowns, gloves, masks, and caps. Despite the fear, her overriding memory was sadness for her young patients dying from the disease. The medical community in San Francisco, she noted, showed a strong spirit of perseverance and a desire to help.

Journey into Oncology and Global Health in Uganda

After a chief residency, which sparked her interest in management, Dr. Desmond-Hellmann chose to specialize in oncology. She was drawn to the field's unique blend of compassionate patient care and rigorous science, inspired by an oncologist mentor during medical school. In the mid-1980s, medical oncology was somewhat stagnant, with breast cancer treatments, for example, relying on decades-old drugs like CMF (cyclophosphamide, methotrexate, 5-fluorouracil). Dr. Desmond-Hellmann developed an interest in cancer epidemiology, leading her to pursue a Master's in Public Health (MPH) at UC Berkeley, focusing on epidemiology and biostatistics – skills that would later prove invaluable in drug development.

A pivotal experience was her time in Uganda from 1989 to 1991 with her husband, Nick. Funded by the Rockefeller Foundation, they went to study the heterosexual transmission of HIV, a concept then met with skepticism by some in the Western world. Uganda, recovering from the Idi Amin regime, was a challenging and sometimes dangerous environment. Dr. Desmond-Hellmann effectively doubled the number of oncologists in the country, focusing on the adult cancer unit, which was overwhelmed with Kaposi's sarcoma cases linked to HIV. At the time, antiretroviral drugs like AZT were not yet available there. She described the dire situation, with HIV prevalence as high as 50% among 16-year-old girls attending STD clinics. Her clinical observations led to a significant finding: Kaposi's sarcoma on the soft palate was 100% predictive of HIV infection, a crucial diagnostic clue in a resource-limited setting. Their work confirmed high rates of heterosexual HIV transmission, often linked to untreated sexually transmitted diseases (STDs) which created open lesions, facilitating viral entry, especially with high viral loads. The Ugandan government was receptive, launching public health campaigns like "Zero Grazing" to promote monogamy and condom use. The personal toll of witnessing so much death was immense, leading to a triage system for scarce chemotherapy (like Vincristine for KS). Coping involved "leaning in" to help, mutual support with her husband, and taking breaks for rejuvenation.

Pioneering Drug Development at Bristol-Myers Squibb and Genentech

Upon returning to the US, Dr. Desmond-Hellmann initially found it difficult to re-enter UCSF academically, as they lacked a global health program. After a period in private oncology practice in Kentucky, her husband was recruited by Bristol-Myers Squibb (BMS) for HIV drug development. Due to a nepotism clause, she joined BMS as a consultant, initially assigned to drug safety for Taxol (paclitaxel). Taxol, derived from the yew tree, was a novel chemotherapy agent that worked as a microtubule poison. Its development was challenging due to solubility issues and severe allergic reactions caused by its dissolving agent. BMS had revived Taxol after the NCI had shelved it. Dr. Desmond-Hellmann's background in epidemiology and biostatistics, honed in Uganda where she taught herself SAS programming, proved crucial in analyzing Taxol's safety profile, particularly its short, severe neutropenia. Taxol gained approval for ovarian and then breast cancer, becoming a major drug for BMS, with Dr. Desmond-Hellmann eventually leading the Taxol project team.

In 1995, she moved to Genentech, attracted by Art Levinson's vision to build a leading oncology company, despite Genentech struggling at the time. Genentech, considered the first biotech company, was founded on recombinant DNA technology, initially producing human growth hormone and out-licensing insulin. They had also developed TPA (tissue plasminogen activator), a clot-busting drug for heart attacks. Her first project at Genentech was Thrombopoietin (TPO), intended to boost platelet counts, but its kinetics proved problematic for chemotherapy-induced thrombocytopenia.

A major focus became Herceptin (trastuzumab), an antibody targeting the HER2 protein, which is overexpressed in about 25% of breast cancers and associated with a much poorer prognosis. The concept was to block the HER2 growth signal. There was initial skepticism within Genentech and the broader oncology community about the efficacy of antibodies against solid tumors. However, Herceptin proved highly successful, significantly improving survival for HER2-positive breast cancer patients. Its success, contrasted with the simultaneous debunking of high-dose chemotherapy with bone marrow transplant for breast cancer, marked a turning point for targeted antibody therapy.

Genentech also developed Rituxan (rituximab) through a deal with Idec. This antibody targeted the CD20 protein on lymphoma cells and became a cornerstone of lymphoma treatment. Dr. Desmond-Hellmann recalled an instance of tumor lysis syndrome (rapid cancer cell breakdown overwhelming the kidneys) in a Rituxan-treated patient as a stark indicator of the drug's power. Another major development was Avastin (bevacizumab), an antibody targeting VEGF (vascular endothelial growth factor), based on Judah Folkman's theory of angiogenesis (new blood vessel formation) being essential for tumor growth. Dr. Desmond-Hellmann recounted the initial trepidation before the first human dose, fearing systemic collapse of blood vessels. Avastin initially failed in a Phase 2 trial for late-stage breast cancer but later succeeded in Phase 3 trials for colon cancer, extending median survival, albeit at a significant cost that sparked debates about value in healthcare.

Dr. Desmond-Hellmann explained the drug development pathway: starting from a target, choosing a modality (small molecule or antibody), extensive preclinical work (animal models, toxicology, diagnostic development for targeted therapies like Herceptin), filing an IND (Investigational New Drug application), Phase 1 (safety), Phase 2 (dose, schedule, patient selection, efficacy signal), and Phase 3 (large confirmatory trials). She noted the importance of developing diagnostics alongside targeted therapies, a lesson learned with Herceptin where the commercial diagnostic had to be correlated with the clinical trial assay post-hoc.

Leadership in Academia and Philanthropy: UCSF and the Gates Foundation

Following Roche's acquisition of Genentech in 2009, Dr. Desmond-Hellmann was recruited as Chancellor of UCSF. This was a challenging time due to the economic recession. Her vision focused on sound financial management, maximizing assets, and fundraising. UCSF, despite being a state school, received minimal state funding, relying heavily on clinical revenue, NIH grants, and philanthropy. Dr. Desmond-Hellmann found success in philanthropy by clearly articulating UCSF's "hopes and dreams" to potential donors and building trust. Her role involved significant external engagement (about 40% of her time) and internal leadership, managing deans, the hospital CEO, and other key figures. She fondly remembered attending weekly science talks at Mission Bay, a testament to UCSF's vibrant research culture.

In 2014, she transitioned to become CEO of the Bill & Melinda Gates Foundation. Recruited by Bill and Melinda Gates, she was seen as someone who could navigate their sometimes-differing approaches to philanthropy. The Foundation, with around 2,000 employees and an $8 billion annual budget, was a massive operation. A key challenge was translating Bill Gates's "endless appetite" for new initiatives into a coherent strategic plan. She introduced a portfolio management process, similar to what Genentech used, to bring more order to decision-making. Dr. Desmond-Hellmann emphasized that the "people side" and fostering a positive organizational culture were her priorities. She defined culture as creating an environment where employees feel they can do their best work and have agency. She shared anecdotes from Genentech and her practices at the Gates Foundation, such as supporting presenters during tough questioning, to illustrate how leadership shapes culture.

Reflections on Public Health, COVID-19, and Misinformation

Dr. Desmond-Hellmann was leaving the Gates Foundation as the COVID-19 pandemic began. She expressed being "horrified" by the subsequent erosion of public trust in science, the politicization of health, and the spread of misinformation. She believes the US is no better prepared for a future pandemic than it was in 2019. A critical mistake, in her view, was combining the roles of chief scientific advisor and public policy advocate in one person (referencing Dr. Fauci implicitly). She argued that science requires impartiality and a willingness to change views with new data, while advocacy involves driving policy, sometimes with incomplete information. This conflation, she believes, damages trust. She stressed the need for honest, transparent communication about evolving scientific understanding, especially in a fast-paced social media environment where misinformation can thrive if not countered by credible voices.

Discussing the Ivermectin controversy, she highlighted how claims of it curing various cancers are scientifically implausible because cancer is not a single disease; each type has a unique biology requiring specific treatments. She argued that pharmaceutical companies would readily develop and patent a modified version of Ivermectin if it truly were a pan-cancer cure. Dr. Desmond-Hellmann posited that the medical community's dismissive and "elitist" response to Ivermectin's use for COVID-19 (e.g., calling it "horse dewormer") backfired, turning it into an "anti-smarty pants drug" and fueling mistrust. She advocated for a more inclusive public health workforce that engages diverse communities to rebuild trust and improve health outcomes.

The Future of Medicine: AI's Role and Challenges

Currently serving on the board of OpenAI, Dr. Desmond-Hellmann is the only medical professional in that group. She is enthusiastic about AI's potential in medicine. Key areas include: 

1. Accelerating Drug Development: AI could significantly reduce the time and cost of clinical trials by automating laborious paperwork, report generation, and data analysis, potentially shortening a 6-year drug development timeline by two years.
2. Enhancing Post-Market Surveillance: AI can enable more comprehensive and ongoing safety and efficacy monitoring once drugs are on the market.
3. Reducing Clinician Burnout: AI tools could alleviate administrative burdens on doctors and nurses (e.g., chart reconciliation, connecting disparate patient data), allowing them more time for direct patient care.
4. Improving Diagnostics and Biomarker Discovery: AI's success in protein folding (like DeepMind's AlphaFold) is a significant step in pre-preclinical drug discovery. She hopes AI can help identify robust biomarkers, akin to viral load in HIV treatment, which dramatically accelerated HIV drug development. This could lead to more precise patient stratification and tailored therapies.

Regarding liquid biopsies for cancer screening, Dr. Desmond-Hellmann expressed a current skepticism based on available data, primarily due to issues with sensitivity – tumors may not shed enough detectable DNA. While AI might help improve analysis, the fundamental biological challenge remains. She noted that truly effective early cancer detection methods are still few (colonoscopy, Pap smears/HPV vaccine, low-dose CT for lung cancer), and even PSA for prostate cancer requires nuanced interpretation to be beneficial. She remains hopeful that AI could aid in identifying new, reliable biomarkers, perhaps protein-based, for earlier cancer detection, such as in breast cancer.

Conclusion

Dr. Susan Desmond-Hellmann's career is a testament to the profound impact one individual can have across diverse sectors of medicine and science. From facing the unknown during the AIDS crisis to spearheading the development of life-saving cancer therapies and leading global health initiatives, her journey underscores the power of integrating rigorous science with deep compassion and effective leadership. Her reflections on the challenges of public trust, the complexities of drug development, and the transformative potential of AI offer valuable lessons for the future of healthcare. Ultimately, her story is one of relentless pursuit of better health outcomes for all, driven by a commitment to innovation, collaboration, and an unwavering focus on the patient.