Huberman Lab
Avoiding, Treating & Curing Cancer With the Immune System | Dr. Alex Marson
09 Mar 2026
Chapter 1: What is the current state of biology and medicine?
We're living in this amazing moment of biology where we can put a gene that encodes something on the surface of T cells that will make them programmed to search and destroy for cancer cells. Now, this is largely known as CAR T cells, chimeric antigen receptor. This is a receptor that was designed in a lab, does not exist in nature.
When those T cells get re-infused into a patient the way that you get like a blood transfusion, those CARs are directed to go against cancers. Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. My guest today is Dr. Alex Marcin.
Dr. Alex Marcin is a medical doctor and scientist at the University of California, San Francisco. He is developing new ways to reprogram the immune system to cure cancers. Today, we discuss how your immune system works, how autoimmunity works, and how gene editing and other new technologies can be successfully leveraged to defeat childhood and adult cancers.
Dr. Marcin is truly one of a kind in his understanding of the clinical aspects of cancer treatment, the science of the immune system, and, as you'll soon hear, in explaining the things that genuinely increase your cancer risk, many of which are surprising, and the actionable steps that we can all take to reduce our probability of getting cancer.
In addition to the usual factors, smoking, UV light, and environmental toxins such as pesticides, we discuss the actual cancer risks that come from things like eating charred meats, airport scanners, and food additives, and how to gauge your individual level of risk. We also explore gene editing for reversing diseases, which until recently was science fiction, but now is 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 or a close friend or family member in your lifetime. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford.
It is, however, part of my desire and effort to bring zero cost to consumer information about science and science-related tools to the general public. In keeping with that theme, today's episode does include sponsors. And now for my discussion with Dr. Alex Marson. Dr. Alex Marson, welcome.
This is the first time that we're going to have a serious discussion about the immune system, cancer, and gene editing technologies on this podcast. So I'm delighted that you're here. It's also great to see you again. Thank you for having me. Really, really good to see you. It's been a while. Let's start off with the big picture. How are we doing? How's biology looking? How's medicine looking?
Are we on the fast track to much better things? Are we going to slog along for another 10 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's happening right now? Maybe the general public doesn't quite know how excited biologists are about what's possible.
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Chapter 2: How do environmental factors influence cancer risk?
If a bacteria might come into existence or a virus might come into existence that doesn't even exist now in nature, but we might have T cells lying there waiting that could be engaged by those proteins on the surface that viruses would introduce. That's incredible. Would you mind mentioning the role of the thymus? These days I'm hearing more and more about we have a thymus and we lose a thymus.
Would it be beneficial if we could keep our thymus around? So thymus... is actually the reason the T cells are called T cells is the T stands for thymus. And the thymus is an organ that it does sort of shrink as we age, but at least in childhood it sort of lies by your heart. And it is the place where T cells go and a key place of their education.
So they are making these sensors largely at random. And in the thymus, they get cult. They get selected. And the ones that by accident are generated that recognize something that is supposed to be in your body, if the T cell engages a natural target in the thymus, those cells will die. And so what emerges from the thymus should be, and this is not perfect process, but should be things that are...
have emerged at random but then are selected to remove things that recognize your own body targets. There's sort of a negative selection of the stuff that's you so that your immune system doesn't attack you and it knows you from non-you. Yeah, that's exactly right. There's actually both a positive selection and a negative selection. That's exactly the right way to think of it.
the cells will only emerge from the thymus if they have a receptor on their surface that's there. So that's one positive selection. But if it engages with a self-target in the thymus, it gets negatively selected. So what comes out are T cells that are there with sensors in place to recognize things that shouldn't be there. Okay, so your thymus and your T cells get educated in childhood. Yeah.
And that's what you're working with. except that the immune system can adapt and make antibodies to things it doesn't recognize. The antibodies come from the other type of lymphocytes. So now we can talk about the B cells. B cells are this other type of lymphocyte that work in coordination with T cells and they're the antibody producing cells.
So they actually have a similar process where they're generating different antibodies at random through a similar kind of recombination event. They have their own form of selection that they go through. and then those antibodies can then be released into the bloodstream and are the basis for protection against infections after we get them.
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Chapter 3: How does the immune system differentiate between us and non-us?
Because that's the proliferation of the tumor. Certainly, cells propagate their DNA into their daughter cells. I could imagine a situation where every day some of our cells get a mutation, spit off a couple daughter cells, and then those daughter cells are terminal, as we say, right? And they don't create more cells. Is that happening all over the body every day? So how is it that...
the DNA that creates the further propagation gets passed from one cell to the next. I do think this is happening constantly. It's a process that every time a cell is around, especially as it's dividing, there is some imperfection in how the DNA... The DNA has inside each of our cells, if that cell is going to replicate, the DNA has to replicate itself. So you end up with two copies of DNA that...
should be the same, each one being passed on to the two daughter cells of that dividing cell. That process of DNA replication is imperfect and if there's any kind of damage during that process, one of those two copies might end up different than the other one, in which case you end up with a mutation now in one daughter cell and not the other.
If that is deleterious or if it's damaging, which probably most mutations are, those cells might start to die off. Okay, the DNA got messed up, those cells that are carrying that DNA Yeah, they can't take up glucose. They just can't do cell stuff. And there's a lot of control mechanisms in the cell that say something's wrong. Let's send a programmed cell death signal to that cell.
And cells will kind of implode with various processes when something is wrong. And that happens most of the time. The problem is if that change all of a sudden starts to not be damaging but to actually be a signal, okay, now the cell is growing more. It has some benefit that it's accumulated as a result of that mutation. Now that cell will start to divide more.
And that cell that's carrying that first mutation might start dividing more. Both of its daughters now will pass on this mutation that's made it divide more. And if in subsequent rounds it gets a second hit, the combination may go from just cells that are dividing a little bit more to cells that take off and become full-blown cancer. Now there's certain processes that will accelerate that.
One was exposure to things that cause DNA damage. The major one is smoking. When smoking causes chemicals to go into your lungs, the lung cells get exposed to these chemicals that then cause higher amounts of DNA damage, more mutations.
And just as you have more mutations at a higher frequency, you're more likely to accumulate a set of mutations that will gradually go on to cause the generation of cancer. Another way that this process can be accelerated is that some people carry an underlying genetic predisposition to cancer.
So people will likely have heard of the BRCA genes which predispose to breast cancer and other types of cancer. There people start with one copy that's already setting them on a road to higher risk of mutations accumulating and the whole process happens with a higher frequency and so this march towards cancer cells is more likely to occur in people with that type of predisposition.
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Chapter 4: What are the roles of T cells and B cells in the immune response?
avoid the scanner at the airport. Honestly, I do, but I can't say that there's data for that. I feel the same way as you. If I could avoid it, I'd try to minimize. But that's not based on some inside knowledge I have, but I have the same bias of less seems better. Yeah, I mean, I'm not out to get the scanner industry.
I think it's useful for people to hear that, that one can have no formal data, but an understanding of mechanism that leads them to hedge. It's good to know. Are there any mutagens and, well, is a carcinogen and a mutagen the same thing? So they're closely related. Mutagen, I think, means that you're mutating, that you're changing the DNA in the cell. That's the idea.
Those mutations may or may not be linked to cancer, but by virtue of the fact that you're causing more mutations, almost inevitably you're also increasing the risk of cancer, and carcinogens are things that increase the rate of cancer. I love barbecued meat. I don't like barbecue sauce because it's sweet, but I like meat with a char. Yeah, yeah. Is the char bad? I think so.
I mean, I like it too, but yeah. Again, these are balancing decisions in life. Sure. But yes, there's some, there's, I mean, meat in general has been implicated as a potential carcinogen, especially in colorectal cancer. There's some data around that. Yeah, my read of those data, not the char data, but the meat data, it's tricky. This is just my standpoint.
I want to make sure I put brackets around this, that this is my read of the literature, is that many of the studies that looked at meat-rich, red meat-rich diets versus plant-based diets. The problem is a lot of times the red meat-enriched diets had a bunch of other things in them. Sourcing wasn't considered. There was also a lot of starches.
Because nowadays you find people who seem to at least feel better Who knows about the longevity aspect, but feel better eating red meat, fruits and vegetables, limited amounts of starches. So I feel like the nutrition studies are a mess. They're kind of a disaster. I certainly don't have clarity on this. Yeah. Yeah. And it seems like it changes the direction.
I think some things we have pretty good common sense intuition about. Fiber. Yeah. Yeah, ultra-processed foods are probably bad. But I think the balance of exactly what whole foods we're eating probably still needs to be worked out.
How do you think about the data on, like, for instance, food dyes, this is very timely, where a certain food dye at a very, very, very high concentration in laboratory animals creates a significantly higher concentration incidence of tumors and cancers in those animals. But then the amount of food dye that's in the human food is a tiny fraction of that. I'm not trying to get political here.
I just think as a framework for people to think about, there are many carcinogens, I'm sure, right in this environment. I don't doubt that the lacquer on this table, in fact, if that's even what they used, if ingested, could cause cancer. I don't doubt that, right? But I don't know that in its form here, being near it for many hours a day does that. I doubt it. We're not inhaling the table.
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Chapter 5: What is the significance of CRISPR in bacterial immunity?
And little by little by little it was worked out that these repeat sequences actually formed the basis of a kind of immune system for bacteria. Now, we talked about the human immune system. Bacteria are just an individual cell, but they're also susceptible to infections, which is sort of a strange idea. Bacteria cause infections in us, but there's this arms race between organisms.
Everyone's trying to kill everyone else. And so bacteria are constantly being bombarded by certain types of viruses. They're called bacteriophage viruses.
Chapter 6: How does CRISPR technology work in gene editing?
And they've evolved a series of... Bacteria have evolved a series of defense mechanisms to protect themselves from these viruses. CRISPR turns out to be a bacterial defense mechanism against viruses, which is kind of amazing that this thing that has entered into popular culture is a bacteria protection against bacteriophage. Now, why has this caught the world of biology by storm?
Well, what was realized was that the way that CRISPR works to protect against itself, to protect bacteria from viruses is that it can recognize particular sequences of DNA which are virus sequences and would discriminate whether it's a virus sequence or its own bacteria sequence.
And it actually does that by scanning across the DNA and finding something that's recognized as a virus target and not a bacteria target. And when it finds it, it makes a cut. Okay. Now this sounds technical, obscure, but what was recognized, and this became the basis for a Nobel Prize with Jennifer Dowden and Emmanuel Charpentier. Many people around the world have contributed to this field.
What was realized was that this could be repurposed. as a tool, if we take it out of bacteria, we could actually exploit this CRISPR system that had evolved to protect bacteria. And the same rules that allowed bacteria to scan across DNA and find a virus sequence and cut it could be used to scan across any DNA and cut at a particular sequence. That's the power of CRISPR.
Now, why do we care so much about being able to cut a particular sequence? If you can cut, you can also start pasting. You can cut out genes that are limiting, that you don't want to be in a cell. You can start pasting in sequences to replace mutations that cause disease.
We can start pasting in big sequences like the sequence for cars or other types of things that will make T cells more powerful. And I'm focused on T cells, but this is now in every aspect of biology. People are studying this in plants and to make crops that will be drought resistant.
People are studying this in every organ system to understand every type of disease and to build new types of molecular medicines. There's one other feature of CRISPR that's really important in this story. It's not just that this CRISPR can cut at a specific sequence, that it's evolved to cut at virus sequences.
It's the way that it cuts that has made it really catch on in a way that none of these earlier technologies do. So CRISPR, if you think of it as an enzyme that can cut DNA, and it can cut essentially almost any sequence of DNA. So how does it decide which sequence to cut? It does it by actually pairing with an RNA molecule.
So CRISPR, sometimes called Cas9, which is a particular type of CRISPR system, is a combination of a protein, which is a scissor, and then an RNA that sticks to it. And the RNA is what actually programs where that scissor will cut. And what's so special about that is that we actually know with near perfect precision the rules of how an RNA will recognize any DNA sequence.
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Chapter 7: What are the ethical implications of CRISPR on human embryos?
How do you ensure that there aren't downstream effects? I mean, I think what you're getting at with both these questions are unintended consequences. And that's always present, right? I think this has been a major concerted effort for the field of CRISPR. How do you get more and more precise? And it's come a long way, but nothing's perfect, right? So I think we've done a lot.
The field has done a lot of work to test off-targets. If you're programming to cut on one place on chromosome 6, do you accidentally ever cut anywhere else? And there's a range, sometimes some sequences are a little bit more promiscuous than others, but we've gotten quite good at getting more and more precise to say, okay, we're making these high fidelity cuts at one place.
there are still the second risks of bystander effects. Okay, you make a cut, what does the DNA get chewed back and at the neighboring part there's been in some extreme places pieces of chromosomes actually falling off. All these things can happen and I think what we're kind of at a place in a field where now we're thinking about for each disease
a risk benefit of okay, there's always a risk for any medicine of some unintended consequences, we have to be on the lookout for them, we have to know what they are. Most cells as we said that get a mutation don't have a problem, they just die off.
So if you have an unintended consequence most will die but there is always the risk of the unintended consequences and I think as a field we have to be humble about that. That said, the CRISPR world is not static. The story I told you was like the building block of CRISPR. It's a protein scissor that can be targeted to any piece of DNA with an RNA molecule. People...
appropriately thinking, well scissors can cause damage. Maybe that CRISPR molecule should actually be re-engineered not to be a scissor but to do other things. And now people have started engineering it to say, well let's not make it a scissor, let's make it a thing that just introduces a more predictable mutation at a site.
David Liu at Harvard has created these things called CRISPR base editors that doesn't introduce a double-stranded break but actually changes nucleotides in a more predictable way at that site by recruiting a deaminase domain, something that will change DNA nucleotides
when it's recruited to a particular place and you use CRISPR just to recruit that enzyme that makes that mutation at a targeted place. Other people have actually started using epigenetic enzymes.
The DNA doesn't just get enacted by DNA sequences but can actually, pieces of it can be active or inactive and this is called epigenetics where there can be a stable program of things getting turned on or off without any change in the A's and T's and C's and G's.
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Chapter 8: What advancements are being made in cancer immunotherapy?
CRISPR to appropriate cell types and or organs. And then that sort of seeds another question that I'll hold off on about whether we should be banking cells for what's coming. First of all, I just want to pause. This is great. I love this conversation. I do too. I mean, you're taking us to the ā I don't like the phrase bleeding edge. It sounds violent.
But you're taking us to the cutting edge of molecular biology and medicine. And we are peering over into what's next, like what your children and my children and probably our parents also will be able to benefit from in the next 10 years. years, maybe sooner. Yeah, we're really talking about things that are happening now and happening at an accelerating rate.
So you asked, part of what just made me have that reaction, I think you asked one of the key questions for this field of how is this being delivered into cells? So I told you, let me go backwards and then I'll go forward.
I told you that in 2012 I sort of was sitting there thinking about I wanted to study T-cells, the genetic control of T-cells, I saw the power of CAR T-cells, I saw the power of CRISPR, which at that time was being only used in highly artificial immortalized cell lines that grow easily in the lab.
And it just wasn't clear that there would be a way to get CRISPR to work in real T-cells that you would take out of a human blood sample that are not immortalized, that can only stay in a dish for a short amount of time and still retain their function. And I sort of tripled down on this was what my lab was going to do. We were going to figure out a way.
And we went through a long list of different ways that we might deliver. And it wasn't obvious. Actually, a key collaboration early in my career was... another serendipitous run-in. I met Jennifer Doudna through some persistence of my own. And Jennifer Doudna and I sat down and started thinking about how could we team up to take her expertise in CRISPR biochemistry and get it to work in T-cells.
And we settled on this thing that was not at the top of my list of things that would work, but ended up opening up the field. We actually purified the CRISPR protein. So we had protein and RNA that we could make in a test tube. Now we order it off the internet. We can mix them together and we could make these protein RNA complexes and we could suspend that in liquid.
And then what we did is we actually incubated T cells from a blood sample in that liquid. And then the question was how do you get these protein RNA complexes into the cells? And we used this trick that's been around for a long time. As long as it's been around, it sounds magical and no one quite understands how it works.
We put the cells into a device that gives a small electrical current to the T cells. Electroporation. Electroporation. Oh, man, I... During my graduate career, I electroporated a lot of... Well, I can just say it now because I don't do it anymore. Electroporated a lot of brains of intact animals. You inject DNA. It's floating around in the local tissue. You pass some square wave current.
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