The Manosphere Report

0:00We're living in this amazing moment of biology where we can put a gene that

0:03encodes something on the surface of T -cells that will make them programmed to search

0:09and destroy for cancer cells.

0:11Now, this is largely known as CAR T -cells, chimeric antigen receptor.

0:16This is a receptor that was designed in a lab, does not exist in nature.

0:20When those T -cells get re -infused into a patient the way that you get

0:23like a blood transfusion, those CARs are directed to go against cancers.

0:28Welcome to the Huberman Lab Podcast, where we discuss science and science -based tools for

0:33everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford

0:42School of Medicine. My guest today is Dr.

0:45Alex Marson. Dr. Alex Marson is a medical doctor and scientist at the University of

0:49California, San Francisco. He is developing new ways to reprogram the immune system to cure

0:54cancers. Today, we discuss how your immune system works, how autoimmunity works, and how gene

1:00editing and other new technologies can be successfully leveraged to defeat childhood and adult cancers.

1:07Dr. Marson is truly one of a kind in his understanding of the clinical aspects

1:11of cancer treatment, the science of the immune system, and, as you'll soon hear, in

1:16explaining the things that genuinely increase your cancer risk, many of which are surprising, and

1:21the actionable steps that we can all take to reduce our probability of getting cancer.

1:26In addition to the usual factors, smoking, UV light, and environmental toxins, such as pesticides,

1:32we discuss the actual cancer risks that come from things like eating charred meats, airport

1:37scanners, and food additives, and how to gauge your individual level of risk.

1:41We also explore gene editing for reversing diseases, which until recently was science fiction, but

1:47now is a reality. By the end of today's episode, thanks to Dr.

1:51Marson, you'll have the most up -to -date understanding of the state -of -the -art

1:54science for cancer prevention and treatment, knowledge that is certain to impact you or a

1:59close friend or family member in your lifetime.

2:02Before we begin, I'd like to emphasize that this podcast is separate from my teaching

2:06and research roles at Stanford.

2:07It is, however, part of my desire and effort to bring zero -cost -to -consumer

2:11information about science and science -related tools to the general public.

2:15In keeping with that theme, today's episode does include sponsors.

2:18And now for my discussion with Dr.

2:20Alex Marson. Dr. Alex Marson, welcome.

2:24Andrew. This is the first time that we're going to have a serious discussion about

2:28the immune system, cancer, and gene editing technologies on this podcast.

2:33So I'm delighted that you're here.

2:35It's also great to see you again.

2:36Thank you for having me.

2:37Really, really good to see you.

2:38It's been a while. Let's start off with the big picture.

2:43How are we doing? How's biology looking?

2:46How's medicine looking? Are we on the fast track to much better things?

2:50Are we going to slog along for another 10 years before we have cures to

2:54the many concerns that people have about cancer, Alzheimer's, and the rest?

2:57Or are you encouraged by what's happening right now?

3:01I think maybe the general public doesn't quite know how excited biologists are about what's

3:09possible. And maybe we've overpromised.

3:11Maybe in the past we've said we're on the brink of curing disease and people

3:14haven't seen it. But something is materially different right now.

3:18And there is a convergence of so many different ways of understanding biology, but then

3:25not having that stop at understanding, but to actually intervene at the root causes of

3:30disease. And over the course of this conversation, I imagine we're going to talk about

3:35DNA sequencing, understanding cells, but going all the way to rewriting specific DNA sequences inside

3:43of the cells of our immune system, doing this not one at a time, but

3:47testing every gene and understanding pieces of DNA throughout our entire genome to understand what

3:52controls our cells. And then being able to take that information and actually do something

3:56about it to boost our immune system to go after cancer, to balance it for

4:02inflammation and autoimmunity. And that doesn't just have to be sort of searching for a

4:08pill. All of a sudden we can actually talk to our own cells and give

4:12them instructions in the language of DNA and the language of molecular biology.

4:16And in some instances this is being done with CRISPR, but it's also being done

4:21with lipid nanoparticles and vaccines and we're still inventing new ways of giving these instructions.

4:28But all of a sudden medicine is programming the behavior of cells in a way

4:33that's much more directed than was ever conceivable before.

4:38Like there's really a step function in what's imaginable and achievable in medicine.

4:42Super exciting. Do you think that molecular biology and genetic engineering and or AI are

4:50the reasons that things are on this accelerated timeline?

4:54Yes is the answer. All of those things.

4:56I think we can do experiments at a different level of scale.

5:01We can generate data. And then we have the computational tools, including AI, but we

5:06have computational sophistication to actually extract insights from massive amounts of data.

5:15And, you know, I think historically biology was, we were, it was an observational science,

5:21especially if you wanted to study things in humans.

5:23There was... in a way to intervene.

5:25Now all of a sudden we're taking human cells, we're taking them into the lab

5:28and making genetic changes and reading out the consequences and directly being able to observe

5:35the effect. And we have tools to do this with imaging, we have the tools

5:42to do this with DNA sequencing, and we can take this all the way into

5:46clinical trials and see what are the consequences when we actually go after targeted DNA

5:51sequences and make our cells better at treating disease.

5:56Would you mind educating us about the immune system a bit, the adaptive and the

6:01innate immune system, some of the major cell types, because I think those are going

6:04to form the kind of building blocks of our discussions about cancer and other things

6:09today. Our immune system permeates almost every aspect of our health and disease.

6:14It is a system really in the sense of it's involved in every part of

6:20our body that has evolved to protect us, largely to protect us against infections, viruses,

6:27bacteria, fungus, all sorts of foreign invasions.

6:31And our immune system has developed a balance that when it's working properly doesn't recognize

6:39the cells that are supposed to be in the body, but is finely tuned to

6:44recognize signs of things that shouldn't be in the body and to eliminate them.

6:48I mean, at its core, that's the basic job of the immune system.

6:53To recognize us versus non -us.

6:56Exactly. And you talked about the innate versus the adaptive immune system.

7:02Largely what we're talking about are white blood cells.

7:05We're talking about different types of white blood cells that are either inside of tissues

7:10or circulating in our bloodstream that go around and play coordinated and specialized roles in

7:18sensing when something comes in that is not us, that's foreign, that shouldn't be there.

7:24The innate immune system is sort of thought of as the first alarm system, that

7:29something's wrong. And with the innate immune system, which consists of cells like dendritic cells,

7:36macrophages, these are cells that are going around and they're looking for patterns of things

7:43that just generally aren't in human cells.

7:46Some signs of damage, some signs of things that shouldn't be there in a generic

7:51way in a healthy human.

7:53When those first alarm systems get triggered, all of a sudden these innate immune systems

7:58start releasing things, they change their state, and they send off an alarm to other

8:03cells in the immune system.

8:05And then they often recruit in the second arm of the immune system that you

8:09mentioned, the adaptive immune system.

8:12We'll talk a lot about the adaptive immune system today.

8:15And the major players in the adaptive immune system are a group of white blood

8:20cells that are collectively known as lymphocytes.

8:23But we'll talk about B cells and T cells in particular, which are major groups

8:28of lymphocytes. We've been focused heavily on T cells.

8:33T cells play a central role in coordinating the fine -tuning of the immune response.

8:39One of the amazing things about the T cells is that each T cell naturally

8:42in our body is one of the few places where each cell will actually have

8:47a different piece of DNA that's not inherited in our germline sequence.

8:51Each T cell will make its own receptor that is generated largely at random to

8:59go and sense something. And those sensors that get put on the surface of T

9:05cells are there to engage.

9:07And if they're engaged, it's a sign that something has been recognized as foreign.

9:11And so we have this incredible diversity of different T cell receptors that have developed

9:19on our T cells. Each one will have a different, unique receptor on its surface.

9:23Each cell will have a different receptor on its surface.

9:26And the way to think about these receptors is that they're sensors.

9:31When they're engaged, they send a signal to the T cell that, okay, we found

9:35something that you've been programmed to recognize.

9:38And the program is recognized as far and if the immune system is working properly.

9:42And are the genes that these T cells make as these receptors, are those based

9:47on experience of the organism?

9:49Because you said that it doesn't come from the germline, but we should clarify that

9:52the germline is not about infectious germs in this context.

9:55The germline DNA is from the sperm and egg that were your parents.

10:01It became you. There's recombination of those genes.

10:03And then there's you, all, each and all.

10:06And the T cells are making genes that neither your parents necessarily expressed nor that

10:11you were expected to express except based on what?

10:14Exposure to particular pathogens? Like why do they make certain receptors and not others?

10:19Largely random. It's actually, there's the pieces of DNA at this part of the DNA

10:25actually recombine and get pasted together in unique ways.

10:30So it's probabilistic. It's probabilistic.

10:32And that's what allows us to have cells that lying there and waiting for things

10:38that we've never encountered. If a bacteria might come into existence or a virus might

10:43come into existence that doesn't even exist now in nature, but we might have T

10:47cells lying there waiting that could be engaged by those.

10:51And that's what we're trying to do to do to do to do to do