Liquid biopsies for early cancer detection, the role of epigenetics in aging, and the future of aging research | Alex Aravanis, M.D., Ph.D.

**Peter Attia** (0:11)
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My guest this week is Alex Aravanis. Alex is the CEO and co-founder of Moonwalk Biosciences.
I should note up front that I am also an investor in and an advisor to Moonwalk Biosciences. Alex and I were colleagues in medical school, so I've known Alex for a little over 25 years now. Before Moonwalk, Alex was Illumina's chief technology officer, the SVP and head of research and product development. And under his leadership, Illumina launched the industry leading product for generating and analyzing most of the world's genomic data. He developed large genome-based research and clinical applications, including whole genome sequencing for rare disease diagnoses, comprehensive genomic profiling for cancer, and for selected optimal therapies. And the most advanced AI tools for interpreting genomic information. Alex has been the founder of several biotech and healthcare companies, including Grail Bio, where he served as the chief science officer and head of R&D.
At Grail, he led the development of its multi-cancer early screening test gallery, which we'll discuss at length in this podcast. He holds over 30 patents and serves on the scientific advisory board for several biotechnology companies. Alex received his master's and his PhD in electrical engineering and his MD from Stanford University, and his undergrad in engineering from Berkeley. In this episode, we talk about two related things, liquid biopsies and epigenetics. We cover the evolution of genome sequencing and tumor sequencing. We then speak at length about Alex's work with Grail and liquid biopsies, including an understanding of cell-free DNA, methylation, sensitivity specificity, along with the positive and negative predictive value of liquid biopsies. We then get into epigenetics, methylation and the biology of aging.
This is an especially complicated topic, but truthfully, there are few topics in biology today that excite me more than this. And I suspect that my enthusiasm will come across pretty clearly here. So without further delay, please enjoy my conversation with Alex Aravanis. Hey Alex, great to be sitting down with you here today. I kind of wish we were doing this in person, because we haven't seen each other in person in a few months, and even that was sort of a chance meeting. So I guess by way of background, you and I go back over 20 years now, I guess it's 25 years that we both started med school together. It's hard to believe it's been that long, huh?

**Alex Aravanis** (3:40)
Seems like a million years ago, but it also seems like yesterday. Yeah, those were good times.

**Peter Attia** (3:45)
So Alex, one of the things I remember when we first met was that we pretty much clicked over the fact that we were both engineers coming in, and we had a good group of friends that I remember in medical school. And the one thing we had in common is not one of us was a pre-med. We were all kind of whatever the term was they used to describe as non-traditional path to medical school. So let's talk a little bit about just briefly your background. You came in as an electrical engineer, and then you did a PhD in a lab of a very prominent scientist by the name of Dick Chen.
Maybe tell folks a little bit about what you did in that work and what it was that got you excited enough about science to deviate off the traditional MD path.

**Alex Aravanis** (4:23)
Yeah, my PhD was in electrical engineering, and Stanford has a cool configuration on the campus where the engineering school is literally across the street from the medical school. And so over time, I became more and more interested in applying signal processing techniques, circuit design, imaging, AI, things like that, but the problems in medicine that were more interesting to me than some of the traditional engineering products and things like that. Met a world famous neuroscientist, name as you mentioned, Dick Chen, who was very interested in fundamental questions about the quantum unit of communication in the brain, which is the individual synaptic vesicle. And there was a question of just what did it look like and how did it operate? And it was the beginning for me of just applying these engineering tools to really important questions in biology and helping answer them. That first story was a great article in Nature where we definitively answered the question of how that quantum is transmitted between cells.