#346 - Scaling biotech and improving global health: lessons from an extraordinary career in medicine | Susan Desmond-Hellmann, M.D., M.P.H.
Dr. Susan Desmond-Hellmann, a physician, oncologist, biotech leader, and former CEO of the Bill and Melinda Gates Foundation, discusses her extraordinary career, from the AIDS crisis and drug development (Herceptin, Avastin) to global health leadership and the future of medicine, including AI's role.
Deep Dive Analysis
14 Topic Outline
Early Medical Training and the AIDS Crisis at UCSF
Experiences Treating HIV-Related Cancers in Uganda
Transition to Biotech and Early Work on Taxol
Genentech's Origins and Recombinant DNA Technology
Pivotal Role in Herceptin Development at Genentech
Rise of Antibody-Based Cancer Therapies: Rituxan and Avastin
The Step-by-Step Drug Development Process
Ethical and Economic Controversy of Avastin's Cost
Leadership as Chancellor at UCSF: Financial Strategy and Fundraising
Lessons from Leading the Bill and Melinda Gates Foundation
Building an Empowering, Values-Driven Organizational Culture
Erosion of Public Trust in Science During COVID-19
The Role of AI in Transforming Medicine and Drug Development
Challenges and Opportunities in Early Cancer Detection
10 Key Concepts
Pneumocystis carinii pneumonia (PCP)
A rare lung infection that immunosuppressed patients could get, commonly seen in early AIDS patients, indicating severe immune compromise and bringing patients to medical attention.
Kaposi's sarcoma (KS)
An unusual purple-colored tumor, very visible externally and internally, common in early AIDS patients in San Francisco and Uganda, serving as a visible marker of HIV infection and immune status.
Recombinant DNA Technology
A genetic engineering process used to teach cells to produce specific proteins, like human growth hormone or insulin, in high amounts, which are then purified for medicinal use, enabling the creation of 'biologic' drugs.
Antibody-based Therapies (Naked Antibodies)
A type of drug therapy that uses antibodies (proteins that fight disease in the body) to target specific proteins on cancer cells, aiming to turn off growth signals or directly destroy the cells, often without a chemotherapy payload.
HER2 (Human Epidermal Growth Factor Receptor 2)
A protein overexpressed in about one in four women with breast cancer, which drives cell growth and is associated with a worse prognosis; targeted by drugs like Herceptin to shut down growth signals.
VEGF (Vascular Endothelial Growth Factor)
A primary factor that promotes the growth of new blood vessels, essential for tumors to grow larger than a certain size; targeted by anti-angiogenic drugs like Avastin to starve tumors of blood supply.
Phase One Clinical Trial
The initial stage of human testing for a new drug, focused solely on determining the drug's safety, identifying a safe dose range, and observing for side effects in a small group of patients.
Phase Two Clinical Trial
The second stage of human testing, which aims to find the right dose and schedule for a drug, identify the appropriate patient population, and gather preliminary data on efficacy, preparing for larger trials.
Phase Three Clinical Trial
The final stage of human testing, a large-scale study designed to confirm the drug's efficacy, monitor side effects, compare it to standard treatments, and collect information for regulatory approval.
Tumor Lysis Syndrome
A potentially life-threatening complication where a large number of cancer cells are rapidly killed and release their contents into the bloodstream, overwhelming the kidneys and causing electrolyte imbalances, often indicating a highly effective cancer treatment.
13 Questions Answered
In 1982, it was known that something was happening, especially to gay men, with initial indications appearing in 1981. Patients often presented with Pneumocystis pneumonia and Kaposi's sarcoma, and medical staff initially used extreme precautions due to unknown transmission.
HIV prevalence was in the double digits across the country. For 16-year-old girls attending STD clinics, there was a 50% chance of being HIV positive, often from their first and only sexual partner.
The high heterosexual transmission was due to a combination of very high viral loads in infected individuals and the high frequency of untreated sexually transmitted diseases like herpes and chancroid, which caused open lesions that significantly increased transmission risk.
The field was stifled with few new chemotherapy drugs for common cancers like breast cancer, relying on decades-old therapies. There was a growing interest in cancer epidemiology and understanding the viral link to cancer.
Genentech pioneered using genetic technology to produce large protein-based medicines like human growth hormone and human insulin, which were previously sourced from cadavers or animals, offering safer and more effective treatments.
Antibodies were largely considered 'hype' that had over-promised and flopped in earlier attempts, with a prevailing dogma that they were not powerful enough to treat solid tumors effectively.
For targeted therapies, a diagnostic test is crucial to identify patients who will benefit from the drug, and it must be developed and approved in parallel with the therapeutic to ensure appropriate patient selection.
Avastin, priced at around $100,000, extended median survival by about eight months for metastatic colon cancer patients, leading to debates, particularly in the UK, about whether the survival benefit justified the high cost based on quality-adjusted life year thresholds.
UCSF's primary revenue streams include clinical income from its hospital system, NIH-driven grant income (including overheads), other grant income, and philanthropy, with very little coming from state funding or tuition.
AI can significantly accelerate drug development by making preclinical stages faster, reducing the duration of clinical trials (potentially by years) by streamlining labor-intensive paperwork and improving safety monitoring through ongoing, real-world data collection.
AI can decrease the burden on caregivers and families by providing tools that simplify tasks like chart reconciliation and connecting disparate data points, assisting at the bedside, and making health system transitions smoother.
Cancer is not a single disease; each type of cancer, and even subtypes within the same anatomical location, has distinct biologies. A single drug curing multiple, biologically diverse cancers is an impossibility.
Based on current data, liquid biopsies have generally been viewed with pessimism due to insufficient sensitivity, meaning they often don't detect enough circulating tumor DNA to be reliably effective for early detection.
30 Actionable Insights
1. Separate Science and Advocacy
To maintain public trust during health crises, separate the roles of scientific communication (impartial reporting of facts) and public health advocacy (driving policy), as combining them can erode confidence.
2. Cultivate Empowering Culture
Strive to create a workplace culture where the atmosphere brings out the best in employees and empowers them with ownership to tweak the environment if it doesn’t meet that standard.
3. Uphold Ethical Values
Consistently uphold and vocalize core ethical principles and company values in all decision-making processes, even if not the primary decision-maker, to reinforce a strong and principled organizational culture.
4. Prioritize Self-Care, Avoid Martyrdom
To sustain well-being in demanding roles, avoid the mindset of martyrdom and actively prioritize self-care through breaks, travel, and social activities, ensuring spirits are kept up.
5. Lean Into Helping Others
When faced with overwhelming sadness or difficult situations, cope by actively ’leaning in’ to help others, finding joy and purpose in contributing to their well-being, even if it’s just providing comfort or a listening ear.
6. Develop Specific Biomarkers
Focus on developing specific biomarkers for disease subtypes, similar to viral load for HIV, to enable highly targeted clinical trials with fewer patients and more obvious clinical benefit from personalized remedies.
7. Streamline Trials with AI
Utilize AI to streamline the labor-intensive aspects of clinical trials, like report generation, to accelerate drug development and ensure that the time taken is focused on patient benefit rather than administrative tasks.
8. AI for Continuous Safety Monitoring
Use AI to enable continuous, ongoing safety monitoring for every patient on a drug, vastly expanding safety data beyond the limited scope of initial clinical trials.
9. Reduce Burnout with AI Tools
Implement AI-powered tools in healthcare to decrease the administrative and cognitive load on caregivers and families, aiming to reduce burnout and enhance the overall care experience.
10. Integrate Health Crisis Combat
To effectively combat global health crises, integrate epidemiology, direct patient care, and policy-making, as demonstrated by the lessons learned from treating HIV-related cancers in Uganda.
11. Balance Finance, Science, Culture
In leadership roles at health research institutions or global health initiatives, balance financial constraints with scientific progress and actively work on building a strong organizational culture.
12. Fundraise with Shared Excitement
To be an effective fundraiser, share your hopes and dreams, express genuine excitement about your mission, and actively ask potential donors about their passions to find common ground.
13. Build Trust Through Prudence
Cultivate a reputation for business acumen and a commitment to using resources wisely, as this builds trust with donors and stakeholders, particularly during difficult financial periods.
14. Fill Information Vacuums
Do not leave an information vacuum in public discourse; actively engage and provide factual information to prevent misinformation from taking root, especially on social media platforms.
15. Be Transparent About Science Changes
When scientific understanding evolves, be honest and open about what has changed and how, as this transparency is vital for building and maintaining public trust.
16. Coach and Support Team
In leadership, actively support team members during challenging interactions by offering non-verbal encouragement, subtly intervening to create space, and demonstrating a clear desire for their success.
17. Prioritize Colon, Prostate Screening
Advocate for and utilize effective screening and early detection methods for colon and prostate cancer, as these diseases are largely preventable and should not be among the leading causes of cancer death.
18. Utilize Proven Early Cancer Detection
Actively engage in proven early cancer detection methods such as colonoscopy, Pap smears (and HPV vaccination), and spiral CT scans for lung cancer to improve health outcomes.
19. Simplify Complex Medical Algorithms
Look for opportunities to simplify complex but effective medical algorithms, such as prostate cancer stratification, into user-friendly, turnkey solutions for both patients and physicians, potentially forming the basis of a new company.
20. Broaden Public Health Workforce
To improve public health efforts, broaden the definition of the public health workforce to include diverse individuals like farmers and community members who have direct experience with relevant issues.
21. Frame Health Universally
To gain broad support for public health initiatives, frame them around the universal desire for personal and family health, making the message real and accessible to everyone, not just an ‘ivory tower’ concept.
22. Establish Patient Registries
For new treatments, especially in novel areas, establish comprehensive patient registries to track long-term outcomes and safety, providing robust data for regulatory scrutiny and ongoing understanding.
23. Leverage Diverse Skills
Understand that skills gained from diverse academic backgrounds, such as epidemiology and biostatistics, can be highly valuable and transferable to other fields like drug development and clinical trials.
24. Develop Backup Strategies
When a primary career or research plan falls through, proactively seek alternative educational or professional paths, like pursuing a master’s degree, to ensure continuous progress and avoid wasted time.
25. Be Resourceful, Self-Teach Skills
When faced with a lack of resources, be resourceful by teaching yourself necessary skills, such as SAS programming, to overcome limitations and achieve your objectives.
26. Identify Career Enjoyment
Pay attention to early career experiences, like a chief residency, to identify what you truly enjoy, such as managing and helping people succeed, as this can be a strong indicator for future career paths.
27. Listen to Mentees, Value Serendipity
When mentoring, actively listen to students to understand their thoughts and remind them about the important role serendipity can play in shaping their career paths.
28. Attend Informal Science Talks
Make time to attend informal science talks or learning events, as this allows you to stay engaged with scientific progress and fosters a culture of continuous intellectual curiosity.
29. Understand Pharma Profit Motive
Recognize that pharmaceutical companies would eagerly pursue and patent any truly curative, broadly effective drug, as such an innovation would generate immense profits, countering claims of suppression.
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8 Key Quotes
If you love medicine, and I do, and you love patients, and I do, it's the combination of you get to call on your compassion gene and your nerdy science gene.
Susan Desmond-Hellmann
The sense of how bad HIV was before antiretrovirals. It's impossible to overstate it. Just impossible.
Susan Desmond-Hellmann
It's the description of science as a beautiful, compelling hypothesis slayed by an ugly fact.
Peter Attia
Work never fills in for home. Ever. It never makes up for a bad home.
Susan Desmond-Hellmann
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.
Susan Desmond-Hellmann
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.
Peter Attia
The nature abhors a vacuum. So if you say I'm not going to kick off people... but I'm not going to remain silent. Here's what I know about that thing... I think that the absence seeds that space to people.
Susan Desmond-Hellmann
Ivermectin might be a horse dewormer. It also happens to be... 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.
Peter Attia