Thank you to one commenter for introducing me to this totally awesome interview of Dr. Alex Marson, conducted by Dr. Andrew Huberman. It’s a two and a half hour video interview where they discuss a wide range of aspects associated with the genetic engineering revolution occurring today in all subfields of biology. They speak of the general cancer revolution, then they turn to the prostate cancer revolution.
It begins with a quick overview of what Dr. Marson describes as a complete shift in the attack on cancer in general, and prostate cancer in particular owing the past discovery of DNA, the historical mapping of the human DNA, DNA sequencing, and finally the series of lucky circumstances surrounding the ability to edit DNA right at the time when human curiosity was ready for it.
The DNA editing tool is CRISPR, as I have described in detail elsewhere. Dr. Marson does a good job of recapping what I had to say about it, and he continues with how he proceeded to work with a key discoverer in the CRISPR field. Here are the segments of the program as parsed by the source website.
Watch them all for a great background it what is going on, or skip to the one that starts at 1:22:17 to jump ahead to the discussion about Prostate Cancer.
“Recent Science Fiction has become Reality.”
- 00:00:00 Alex Marson
Dr. Marson, “We are living in this amazing moment in Biology where we can put a gene which encodes something on the surface of T-cells that will make them programmed to search and destroy for cancer cells. This is largely known as CAR T-cells, Chimeric Antigen Receptor T cells. This is a cell that is designed in a lab, does not exist in nature. When those cells get reinfused into a patient, like a blood transfusion, Those CARs are directed to go against cancer.“
Our Host, Dr. Huberman, who runs his “Huberman Lab” video/pod cast series, is no slouch either! As a professor at Stanford School of Medicine, Dr. Huberman certainly asks the right questions of Dr. Marson, and has some common research experience which he fondly reminisces about as Dr. Marson discusses things.
Dr. Huberman, “I’m Andrew Huberman, and I am a professor of neurobiology and ophthalmology at Stanford School of Medicine.” After introducing Dr. Marson, Dr. Huberman goes on to say, “. . . we explore gene editing for reversing diseases, which until recently, was science fiction, but today is now a reality.”
“By the end of today’s episode, thanks to Dr. Marson, you’ll have the most up-to-date understanding of the state-of-the-art science for cancer prevention and treatment. Knowledge that is certain to impact you, a close friend, or family member in your lifetime.”
“Something is Materially Different Right Now”
- 00:02:21 Diseases & Current Biological Landscape; AI & Computational Tools
Dr. Huberman, ” And now for my discussion with Dr. Marson. Dr. Alex Marson, welcome.”
Dr. Marson, “Andrew.”
Dr. Huberman, “This is the first time we are going to have a serious discussion about the immune system, cancer, and gene editing technologies on this podcast. So I am delighted that you are here. It’s also great to see you again.”
Dr. Marson, “Thank you for having me. It’s really, really good to see you.”
Dr. Huberman, “It’s been a while. Let’s start off with the big picture. How are we doing? How’s biology looking? How is medicine looking? Are we on the fast track to much better things? Or are we going to slog along for another ten years before we have cures to the many concerns that people have about cancer, Alzheimer’s, and the rest? Or are you encouraged by what is happening right now?”
Dr. Marson, “Maybe there is some, some . . . the general public doesn’t know quite how excited biologists are about what’s possible. And maybe we’ve overpromised. Maybe in the past we’ve said we are on the brink of curing diseases, and people haven’t seen it. But something is materially different right now, and there is a convergence of so many different ways of understanding biology, but not having that stop at understanding, but to actually intervene, and at the root cause of the disease. And over the course of this conversation, I imagine we are going to talk about DNA sequencing, understanding cells, but going all the way to rewriting specific DNA sequences inside the cells of our immune system. Doing this, not one at a time, but testing every gene and understanding pieces of our DNA throughout our entire genome to understand what controls our cells. And then being able to take that information and actually do something about it to boost our immune system to go after cancer, to balance it for inflammation and auto immunity. And that doesn’t have to be some sort of searching for a pill. All of a sudden, we can actually talk to our own cells, and give them instructions in the language of DNA and the language of molecular biology. And in some instances, this is being done with CRISPR, but it’s also being done with lipid nanoparticles, vaccines. And we are still inventing new ways of giving these instructions. But all of a sudden, medicine is programming the behavior of cells in a way that is much more directed than is was ever conceivable before. Like there’s really a stop function in what’s imaginable and achievable in medicine.”
Dr. Huberman, “Super-exciting! Do you think that molecular biology and genetic engineering and or AI are the reasons that things are on this accelerated timeline?”
Dr. Marson, “Yes is the answer. All of those things. I think we can do experiments at a different level of scale. We can generate data. And then we have the computational tools, including AI, but we have computational sophistication to actually extract insights from massive amounts of data and you know I think historically biology was . . . we were . . . it was an observational science, especially if you wanted to study things in humans, there wasn’t a way to intervene. Now all of a sudden we are taking human cells, we’re putting/taking them into the lab, and making genetic changes, and reading out the consequences, and directly being about to observe the effect. And we have the tools to do this with imaging. We have the tools to do this with DNA sequencing. And we can take this all the way into clinical trials and see what are the consequences when we actually go after targeted DNA sequences, and make our cells better at treating disease.”
How the Immune System Works
- 00:05:56 Immune System, Innate vs Adaptive Immune System
Dr. Huberman, “Would you mind educating us about the immune system a bit? The adaptive and innate immune system, some of the major cell types, because I think they are going to form the kind of building blocks about our discussions about cancer and, and other things today. “
Dr. Marson, “Our immune system permeates almost every aspect of our health and disease. It’s a system really, in the sense that it, it’s involved in every part of our body that has evolved to protect us. Largely to protect us from infections, viruses, bacteria, fungus, all sorts of invasions. And our immune system has developed a balance that is, when it’s working properly, doesn’t recognize the cells that are supposed to be in the body, but is finely tuned to recognize signs of things that shouldn’t be in the body and to eliminate them. I mean, at it’s core, that the basic job of the immune system.”
Dr. Huberman, “To recognize us vs non-us?”
Dr. Marson, “Exactly. And you talked about the adaptive vs. innate immune system.
- 00:10:55 Thymus, T Cell Selection; B Cells & Antibodies
- 00:13:23 Sponsors: BetterHelp & Helix Sleep
- 00:16:11 Immune System Health, Sleep, Diet; Genes
- 00:20:56 Childhood Exposure & Allergy Prevention; Autoimmune Reactions
- 00:25:27 Whole Body Immune Response, Cytokines & Fever; Antibiotics
- 00:30:51 Cancer; Mutations & Cell Regulation; Smoking, BRCA Mutations, Sunlight
- 00:38:27 BRAC Mutations, Mutagens, Pesticides
- 00:42:33 Sponsor: AG1
- 00:43:57 X-Rays & Airport Scanners, Carcinogen vs Mutagen, Charred Meat, Food Dye
- 00:49:34 Immune-Based Cancer Treatment, Checkpoint Inhibitors, CAR T-Cell Therapy
- 00:59:04 CRISPR, Immunotherapies
- 01:02:52 Age & Cancer Risk; CAR T-Cells, Targets & Side Effects; Ketogenic Diet
- 01:08:27 CRISPR Discovery & Mechanism
- 01:17:06 CRISPR Precision, Risk & Benefit; CRISPR Technology Evolution
- 01:20:57 Sponsor: LMNT
The Latest on how CRISPR and CAR T-Cell Technology have reached the 3rd Clinical Trial for Prostate Cancer.
- 01:22:17 CRISPR Cell Delivery, Clinical Trials; Treating Early Cancers & Prevention
Dr. Alex Marson expresses fascination about having a conversation today about what was such forward thinking just a few short years ago. He then takes us back to when he was setting up his lab to study CAR T-cells and his desire to join that with CRISPR technology, which at the time was still in its infancy, not working with a wide range of situations that might bring immunology and CRISPR together. Dr. Marson had sought out Dr. Jennifer Doudna, a key CRISPR researcher who won the Nobel Prize in Physics for CRISPR. Together they found a way to combine CRISPR with CAR T-cells using the mysterious process known as electroporation, that the host, Dr. Huberman had first hand experience with.
After that success with Dr. Doudna, Dr. Marson started a company, Arsenal BioSciences, which is now in its third Clinical Trial for solid tumor prostate cancer, either starting to or about to start enrolling patients. Arsenal can do it at industrial scales explains Dr. Marson. The size of the DNA strand they are inserting includes the CAR T-cell, but also includes several additional biomarkers that identify the Tumor Micro Environment (TME), and enhance the power of the CAR T-Cells while in the TME.
I have to say that the reading of all these recent research papers has given me the ability to follow what they are talking about, and I feel their excitement. What they are talking about are advancements in the commercial labs that transcend what I was reading about. That means what the journal papers were finding as road blocks to success have been addressed and somewhat or all solved as the trials advance at Arsenal.
It sure sounds like a legitimate effort to over come the CAR T-cell limitations that were previously preventing blood-based cancer solutions from acting so effectively with PCa.
And of course patient selection starts with the sickest patients with all other options exhausted. But not long after that would be the push would be down the line to treat patients earlier in the progression of the disease. Eventually, it could become a preventative process, available to those who have yet contracted the disease as a guard against getting it.
W o W !!!!
- 01:33:47 Liposomes, Engineered Viruses, Lipid Nanoparticles (LNPs), Vaccines
- 01:39:57 COVID Pandemic & Trust in Science, mRNA Vaccine
- 01:47:51 Sponsor: Function
- 01:49:39 Drug Delivery to Cancer, Immunotoxins, T-Cell Engagers; AI Protein Targets
- 01:55:45 CRISPR Embryo Modification, Ethics; Heritable Gene Editing, Diversity
- 02:05:42 Deep Sequencing Embryos, Diversity; Overcoming Adversity & Resilience
- 02:10:44 Upcoming Therapeutics, Autoimmunity & CAR T-Cells, CRISPR & Gene Function
- 02:17:55 Banking T Cells or iPSCs?, Future of Cell Programming
- 02:24:41 Zero-Cost Support, YouTube, Spotify & Apple Follow, Reviews & Feedback, Sponsors, Protocols Book, Social Media, Neural Network Newsletter
These are the kinds of things I have been hoping for ! Can a generalized shot become available for Prostate Cancer therapy? Or at least an autotransfusion-oriented process that conditions my T-Cells to fight my PCa? Can it get down the line enough so that AS patients can take advantage of the technology? Can it happen in just 5 years?
BEST OF SCIENCE FOR EVERYONE !
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