<p><a href="https://www.google.com/url?q=https://peterattiamd.com/alexaravanis/?utm_source%3Dpodcast-feed%26utm_medium%3Dreferral%26utm_campaign%3D241902-pod-alexaravanis%26utm_content%3D241902-pod-alexaravanis-podfeed&source=gmail-html&ust=1708122062309000&usg=AOvVaw2R6KWcag952NdPqq-WOCNQ" rel="noopener noreferrer" target="_blank">View the Show Notes Page for This Episode</a></p> <p><a href="https://www.google.com/url?q=https://peterattiamd.com/subscribe/?utm_source%3Dpodcast-feed%26utm_medium%3Dreferral%26utm_campaign%3D241902-pod-alexaravanis%26utm_content%3D241902-pod-alexaravanis-podfeed&source=gmail-html&ust=1708122062309000&usg=AOvVaw0J8mvamxJPyEnE6RMhHDy5" rel="noopener noreferrer" target="_blank">Become a Member to Receive Exclusive Content</a></p> <p><a href="https://www.google.com/url?q=https://peterattiamd.com/newsletter/?utm_source%3Dpodcast-feed%26utm_medium%3Dreferral%26utm_campaign%3D241902-pod-alexaravanis%26utm_content%3D241902-pod-alexaravanis-podfeed&source=gmail-html&ust=1708122062309000&usg=AOvVaw1UdXhQ4tW_GNc56aGza8lI" rel="noopener noreferrer" target="_blank">Sign Up to Receive Peter's Weekly Newsletter</a></p> <p>Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging.</p> <p><strong>We discuss:</strong></p> <ul type="disc"> <li>Alex's background in applying engineering to problems in medicine [3:15];</li> <li>A primer on human genetics, and the history and current landscape of DNA sequencing [11:00];</li> <li>The advent and evolution of liquid biopsies for early detection of cancer [23:15];</li> <li>The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15];</li> <li>The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00];</li> <li>Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00];</li> <li>DNA methylation explained [58:15];</li> <li>Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45];</li> <li>The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00];</li> <li>The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00];</li> <li>Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45];</li> <li>The role of epigenetics in aging [1:39:30];</li> <li>How cell-free DNA methylation patterns can help identify a cancer's tissue of origin [1:45:30];</li> <li>Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and</li> <li>More.</li> </ul> <p>Connect With Peter on <a href="https://www.google.com/url?q=https://twitter.com/PeterAttiaMD&source=gmail-html&ust=1708122062309000&usg=AOvVaw19LzSmYccfHYcRBUY5kZpv" rel="noopener noreferrer" target="_blank">Twitter</a>, <a href="https://www.google.com/url?q=https://www.instagram.com/peterattiamd/&source=gmail-html&ust=1708122062309000&usg=AOvVaw3TR0Dt8TtHs9glgtIXvpgt" rel="noopener noreferrer" target="_blank">Instagram</a>, <a href="https://www.google.com/url?q=https://www.facebook.com/peterattiamd/&source=gmail-html&ust=1708122062309000&usg=AOvVaw15ws3l8xDqVWQ4dGdNWvUc" rel="noopener noreferrer" target="_blank">Facebook</a> and <a href="https://www.google.com/url?q=https://www.youtube.com/channel/UC8kGsMa0LygSX9nkBcBH1Sg&source=gmail-html&ust=1708122062309000&usg=AOvVaw0mGnZY79ajJKvdvU7r-G5e" rel="noopener noreferrer" target="_blank">YouTube</a></p>
Actionable Insights
1. Explicit Patient Consent for Screening
Physicians should explicitly discuss the implications of screening tests, including the positive predictive value and potential for false positives, with patients before testing. This empowers patients to understand the demands of follow-up and make informed decisions, including declining the test.
2. Prioritize Screening Specificity
When developing or evaluating population-wide screening tests, prioritize high specificity (e.g., <1% false positive rate). This prevents unnecessary follow-ups for benign conditions, which can be a significant burden.
3. Consider Multi-Cancer Blood Test
Consider adding a multi-cancer early detection blood test, such as Grail’s Gallery, to standard-of-care screening. This can double the number of cancers detected, especially for those without existing screening methods.
4. Understand Liquid Biopsy Function
Recognize that liquid biopsies are functional assays, detecting cancers actively growing, dying, and shedding DNA into the blood. This means they may not detect small, encapsulated, or indolent tumors that are not shedding DNA.
5. Negative Test, Better Prognosis
If a cancer is undetectable by a liquid biopsy, it correlates with a very good outcome, suggesting the cancer is less dangerous or existing care is effective. The test primarily detects dangerous cancers associated with higher mortality.
6. Healthy Lifestyle for Methylation
Engage in healthy lifestyle choices like not smoking, regular exercise, and maintaining a healthy weight. These behaviors are correlated with more favorable methylation patterns, which are crucial for cellular function and aging.
7. Build to Understand
Adopt the engineering principle: if you can’t build it, you don’t truly understand it. Apply this by conducting experiments to test if you can make a concept work, even in biology, to deepen your understanding.
8. First-Principles Learning
Approach problems from first principles, asking if you truly understand how something works. Design experiments that guarantee new learning about the system, regardless of hypothesis confirmation or rejection, avoiding experiments that yield no new knowledge.
9. Exhaustively Evaluate Methods
When tackling a complex problem, exhaustively evaluate every potential method or feature, rather than focusing on a single preferred approach. This ensures a comprehensive understanding and identification of the most effective solution.
10. Solve or Disprove
Approach challenging problems with the mindset that you will either figure out how to achieve the goal or definitively prove that it cannot be done. This provides clarity and direction in research and development efforts.
11. Consider NIPT for Trisomies
If pregnant, consider Non-Invasive Prenatal Testing (NIPT) to screen for trisomies (e.g., chromosome 21, 18, 13) using cell-free DNA in the blood. This highly sensitive and specific method can reduce the need for invasive procedures like amniocentesis.
12. Support Podcast, Gain Knowledge
Subscribe to the premium membership at peteratiyahmd.com/subscribe to support ad-free content and gain exclusive member-only benefits. This helps take your knowledge of health and longevity to the next level.
13. Anticipate Rejuvenation Therapies
Stay informed about advancements in rejuvenation therapies, as experts anticipate treatments for specific organs, tissues, and cell types within the next decade. These could improve health span and resistance to diseases like cancer.