#06 - D.A. Wallach: music, medicine, cancer screening, and disruptive technologies
Peter Attia and D.A. Wallach discuss D.A.'s journey from musician to investor, the evolution of the music industry (MySpace vs. Facebook, Spotify's impact), and the future of medicine. They delve into cancer screening, liquid biopsies, and the potential for a "singularity" in biomedicine.
Deep Dive Analysis
16 Topic Outline
D.A. Wallach's Background and Early Music Experiences
Chester French's Formation and Shift to Online Music
MySpace's Role in Artist Discovery and Its Design
Comparing Facebook's and MySpace's Underlying Philosophies
D.A.'s Intellectual Development and Approach to Learning
Musical Influences and Drumming Techniques
Disruption of the Music Industry by Piracy and iTunes
Spotify's Business Model and Artist Compensation
Healthcare's Resistance to Technological Disruption
D.A.'s Vision for a Biomedicine Singularity
Impact and Future of the Human Genome Project
Liquid Biopsies for Early Cancer Detection: Grail's Approach
Glimpse's Nanoparticle-Based Cancer Detection Method
Challenges of Cancer Screening: Sensitivity and Specificity
Future of Personalized Diagnostics and Risk Stratification
Immune System, Inflammation, and Allergy Treatments
8 Key Concepts
Musical Speaking
Singing is essentially a controlled form of musical speaking, where one learns to control pitch and airflow with fine-tuned physical processes. This perspective can make singing easier by reframing it as an extension of natural speech.
Artist's Artist
This term describes a musician whose work primarily resonates with other musicians or those with deep musical understanding, rather than a broad mainstream audience. Chester French was identified as an 'artist's artist' because their fans tended to be musically inclined.
MySpace Top Eight
A feature on MySpace where users could publicly display their eight favorite friends or artists. This became a coveted spot for bands to gain visibility, as being in a famous artist's top eight could lead to significant fan discovery.
Complex Adaptive Systems
A category of systems, including economies, weather, and physiological systems, that share characteristics of complexity and may eventually be described by overarching predictive theories. The Santa Fe Institute is a key organization for studying these systems.
Biomedicine Singularity
D.A. Wallach's vision of a future moment when complex biological systems can be digitally represented and simulated at zero marginal cost. This would allow for rapid, cost-free, intervention-based experiments, profoundly accelerating our understanding of biology and disease.
Synthetic Biomarker (Glimpse)
An engineered nanoparticle designed to be introduced into the body, circulate, and break apart upon encountering specific disease-related enzymes, releasing smaller fragments detectable in urine. This approach aims to generate a larger, more easily detectable signal for early disease, such as cancer.
Needle of Hay in a Haystack
A metaphor used to describe the extreme difficulty of detecting tumor DNA in the blood for early cancer screening. The challenge lies in finding extremely low concentrations of target (tumor) DNA that is genetically very similar to the abundant background (self) DNA.
Swiss Cheese Metaphor (Diagnostics)
A conceptual model for improving diagnostic accuracy by layering multiple imperfect screening tools (like mammograms, DWI MRI, liquid biopsies) and probabilistic risk assessments. Each layer has 'holes' (weaknesses), but when stacked, the holes align less often, increasing overall reliability and reducing false results.
9 Questions Answered
Parents can foster musical curiosity by not negatively sanctioning questions or 'why' questions, and by providing an environment for free exploration, such as allowing a child to experiment at a piano for 30 minutes daily before introducing formal theory.
MySpace allowed for viral cultural permeation through features like legal spamming, a 'top eight' friends list that incentivized artist promotion, and extensive user freedom in page design, enabling users to express identity and connect with like-minded communities.
Piracy decimated the music industry's revenue by allowing free music sharing, while iTunes, pioneered by Steve Jobs, further disrupted it by unilaterally controlling music distribution and becoming the sole dominant retailer, reducing record labels' leverage.
Spotify keeps 30% of the monthly subscription fee, with the remaining 70% distributed pro rata to music originators (record labels, publishers, and artists) based on the amount of time a user spends listening to each song.
Healthcare primarily relies on labor, with hospitals and payers having low profit margins, and pharmaceutical companies taking significant financial risk for innovation. Additionally, the industry is fragmented by numerous regulatory bodies, and technology's ability to deliver substantial new dividends beyond existing progress is unclear.
D.A. Wallach envisions a moment where complex biological systems can be digitally represented and simulated at zero marginal cost. This would enable rapid, cost-free, intervention-based experiments, profoundly accelerating our understanding of biology and disease.
The main challenge is finding extremely low concentrations of tumor DNA (a 'needle of hay in a haystack') among self-DNA, and then accurately distinguishing between aggressive cancers and preclinical tumors that the immune system might naturally clear.
Sensitivity refers to a test's ability to correctly identify those with the disease (true positives), while specificity refers to its ability to correctly identify those without the disease (true negatives). A test with high sensitivity but low specificity can still be a poor test, as it might incorrectly identify many healthy individuals as having the disease.
The change was due to the statistics of false positives. Even with a 73% sensitivity, a positive mammogram for a woman in the general population (with a low incidence of breast cancer) still results in a sub-1% chance of actually having breast cancer, leading to unnecessary follow-up tests and anxiety.
14 Actionable Insights
1. Adopt Bayesian Thinking for Diagnostics
Understand that the utility of a medical screening test depends on your prior probability of having a disease (e.g., genetic risk). A positive test result updates your likelihood, but its significance varies greatly based on your initial risk, not just the test’s sensitivity.
2. Prioritize Test Specificity
When evaluating diagnostic tests, prioritize high negative predictive value (specificity) to avoid false negatives, meaning you never want someone with cancer to be told they don’t have it. You can tolerate some false positives (people without cancer told they do) if the follow-up is manageable.
3. Layer Diagnostic Tests Strategically
Combine different screening tools, like mammography, DWI MRI, and future liquid biopsies, to leverage each test’s strengths and weaknesses. Use liquid biopsies as confirmation rather than leading candidates, especially for conditions requiring invasive follow-up.
4. Focus on Theoretical Frameworks
When encountering a new subject, prioritize understanding its theoretical framework or ‘skeleton’ rather than getting lost in details. This approach helps grasp the underlying structure and how things work.
5. Nurture Children’s Curiosity
Instead of teaching curiosity, focus on not stifling it, as children are born with it. Avoid sanctioning questions or ‘why’ questions to foster an environment where their natural inclination to understand is fed, not suppressed.
6. Balance Rote Practice with Exploration
When learning an instrument or any skill, start by playing around and exploring without a rigid framework before introducing theory. Theory becomes an ‘amazing gift’ that answers questions you’ve already encountered through exploration, rather than an imprisoning set of rules.
7. View Technical Skill as More Colors
Embrace learning technical skills in any creative field, as they provide ‘more colors to paint with’ and expand expressive options without diminishing authenticity. It doesn’t cost anything to gain more ways to articulate your ideas.
8. Develop Singing as Musical Speaking
Approach singing by thinking of it as ‘musical speaking,’ controlling pitch deliberately. This mental reframing can make learning to sing easier and improve vocal control, similar to how physical activities are mastered.
9. Prioritize Preventable Suffering
Focus efforts and investments on reducing suffering from preventable diseases and conditions that afflict people prematurely or in the second half of life. This pragmatic approach addresses immediate human health challenges.
10. Evaluate Tech: Short-Term Over, Long-Term Under
When assessing new technologies like genomics or blockchain, recognize that their short-term impact is often overestimated, while their long-term, transformative potential is frequently underestimated. Focus on the collective intelligence and effort being directed towards the technology.
11. Advocate for Rapid Standard of Care
Physicians and the community should actively work to streamline the process by which definitive scientific advancements, like new medical treatments, become standard of care for all patients everywhere, overcoming bureaucratic hurdles.
12. Encourage Drumming for Kids
For children learning drums, emphasize that they don’t necessarily need to know musical material as well as other instrumentalists. As long as they can quickly learn or figure out a beat, they can play along, which can make it more enjoyable and less practice-intensive.
13. Connect with D.A. Wallach
If you are a ‘genius’ or have an interesting, novel idea that could be deemed genius, reach out to D.A. Wallach via his Twitter (@DAWallach), Instagram (@DAWallach), or website (DAWallach.com).
14. Listen to ‘Time Machine’ Album
Explore D.A. Wallach’s music by listening to his most recent solo album, ‘Time Machine,’ which was released around 2016.
8 Key Quotes
The future is already here, it's just not evenly distributed.
D.A. Wallach (attributing it to venture capitalists)
Singing is just a musical speaking.
D.A. Wallach
It's just going to give you more colors to paint with. It doesn't cost you anything. It just, it just gives you more things that you can say with those ideas you've got.
Herbie Hancock (as quoted by D.A. Wallach)
Facebook is a little bit totalitarian, not necessarily in a bad way... it doesn't have a lot of flavor.
D.A. Wallach
By the time cancer becomes visible on an imaging study, you can make the case you've lost the war.
Peter Attia
The number one risk factor for all diseases is age.
D.A. Wallach
The pithy aphorism that I think applies to genomics and a lot of things in technology is that it is probably short-term overestimated and long-term underestimated.
D.A. Wallach
You never want someone who has cancer to be told they don't have cancer. You can tolerate some people who don't have cancer being told that they do.
D.A. Wallach