Exosomes, Stem Cells, Ketamine ＆ VR — Dr. Melissa Selinger

My friend, Dr. Melissa Selinger is a Doctor of Neuropsychopharmacology who has done actual research on using psychedelics and virtual reality for treating things like depression, anxiety, and PTSD. A huge frontier where there are all kinds of potential, and very little actual scientific research has been done here so far. It’s an exciting frontier to be able to help a lot of people who we don’t have any real idea how to help otherwise.

I’m super thrilled about that and the potential for it. It’s great to get to talk to somebody who knows what state of the art there is. Melissa knows a lot about all kinds of things that I don’t know anything about. As you guys know, part of what I love to be able to do is sit down with somebody who has a lot of knowledge and experience in something that I don’t know about, pick their brain, try and break it down, see if I can understand it and take you guys along for the ride so that we can all learn.

Carcinogens, teratogens, exosomes, stem cells, cytokines, CRISPR, gene editing, all these are things that we talk about in this conversation. A lot of it is me trying to get her to explain in layman’s terms what this stuff is and how it works. There is incredible potential here. If you were ever interested in what’s possible in stem cell therapy, you’re going to want to learn about exosomes and her experience with that. A couple of biotech startups had some ups and downs in that and learned a lot. I’m thrilled to be sharing our conversation with you. Enjoy this episode.

Pablos: I’m going to explain what I know, which is not very much, and you could tell me if I’m full of shit. Sound good?

Melissa: Yeah.

Human bodies are made up of a bunch of cells, most of which are not actually human. They’re like parasites and shit, and microbiome crap and other bacteria are living on your body everywhere. To the extent that there are human cells, the cells are super complex little cities inside. I’ve seen these microscope photos of all the shit inside of a cell, and it’s a lot. It’s complex.

Most people like me have a vague notion that there’s a cell wall, which makes it like a balloon or a bowl or something, and then on the inside is all these goodies, including DNA, RNA, and other stuff. That’s the extent of anybody’s general education on this stuff. There are different kinds of cells. There’re bone cells, blood cells, meat cells, and shit.

There’s a variety of different cells that do different things. All of them started out as stem cells which were basically blank cells. The thing got written into being whatever they’re going to become. You have some of those in an embryo. Over time, as your body is growing, these cells get programmed to be different things. Muscle tissue or brain cells, and then what happens is gamma rays come from space, bombard them, and you get these cell mutations. You end up with all kinds of variations and mutations, and then everybody ends up eventually getting cancer and dying. Is that pretty much the circle of life?

It’s fairly accurate. There’s a lot of causes of cell mutations.

There’re other causes like nicotine.

A lot of just manufacturing in our environments in general are heavily laden with carcinogenic compounds that was a byproduct of the industrial area. Look at California, for example. Everything is a possible carcinogen.

What does carcinogen mean?

It’s a compound that’s able to alter the cell’s DNA structure in a manner that causes aberrant growth, like a malignant tumor. Essentially, the way that cells operate is they have a terminal point of senescence where they die. With cancer cells, they lose that, and they are able to live continuously.

They don’t die like they’re supposed to. They just hang around and replicate. I know some people like that. Carcinogen means that it’s some chemical that you could ingest or come in contact with that can alter the DNA in a cell.

Also, teratogens, which are birth defect causing chemicals in unborn babies as well.

Those are chemicals that the mother could be exposed to, or that the babies get exposed to, or what?

The mothers got exposed to, and then they cross the placental barrier in vivo.

Not every carcinogen does that, but some subset of them are teratogens?

Some subset of them and then there are various prescription drugs that were used during pregnancy that over time were pulled from the market when they realized that some of them cause pretty severe birth defects.

Some people are attempting to live these carcinogen-free lifestyles.

I don’t know if that’s possible in America because there’s such a heavy amount of it. Food in America is heavily chemical-laden and you have everything from the interior of cars and mass-produced furniture are full of anti-flammable chemicals.

If I sit on a couch, that shit’s rubbing off?

It depends on the manufacturer. If you grab a Walmart couch, for example, they have questionable materials and then anything that’s synthetic usually has something. If you have a synthetic vinyl couch or anything plastic, you have plasticizers that leach out over time. Water bottles, for example, the plasticizers that enable the plastic to have a bendiness or softness to them, that leaches out into the water, especially with heat or microwave food and plastic containers. The BPA alternatives are not necessarily safer than BPA.

Even with Fiji Water?

I would say pretty much anything bottled in plastic and then shipped in plastic is.

I thought these plastics were FDA approved for holding food?

FDA approval is still wishy-washy and you have FDA-approved artificial colorings, which may or may not be linked to possible disorders.

We’ve had so much ingestion of artificial coloring, you would think we would know by now.

They say it’s something like 99% of Americans test positive for BPA in their blood at any given time.

I think aluminum cans are lined with plastic anyway.

There’s some lining and the cans. You’re seeing a lot of times, the “BPA-free lining,” but it’s still the way that they’re manufactured. There’s still the joint where it’s sealed as a circular cylindrical piece and there are some metals that leach out. It’s in almost everything.

It’s a losing game and the idea is to try to die before you get sick from ingesting all this crap.

The statistics are something like 1 in 6 Americans will be diagnosed with cancer at some point in their life. It’s a pretty prevalent thing at this point. It’s like a when, not an if, kind of thing.

You have a clear understanding of cell biology. Can you explain what a stem cell is?

With stem cells, if you want to start as far back as the fertilized ova, it gets fertilized with sperm, you get the zygote, which becomes this rapidly dividing mass of cells.

That’s what a zygote is?

Yeah.

It’s just, “Let’s make a bunch of cells.”

At this point, these cells are pluripotent, meaning they can transdifferentiate into all the types of cells in the body. It depends on how far along they’re within.

In the beginning, they could be anything.

That’s the appeal of using fetal cells for stem cells, but obviously, there are ethical concerns with that. It’s not really used anymore.

We used to harvest fetal stem cells.

There was a period where they were using aborted fetal tissue. Some people are very opposed to that. They passed a law that legalized the use of fetal tissue with the exception of a couple of established lines. There’re few countries where everything is fine. Possibly, you can get away with a lot of stuff in China.

Do you think that there’s some important stuff that we’re missing in the US by not allowing that?

For sure, but we’ve turned to other types of tissue. With mass manufacturing, as the regenerative medicine industry is starting to, they’ve found a way to start to scale up to levels that are able to produce pharmaceutical quantities. In some of the tissues that they’re looking at now, they can isolate stem cells from bone marrow, from adipose, which is fat tissue, and then placenta, which is the mesenchymal stem cells that I’ve had the most knowledge about.

One in six Americans will be diagnosed with cancer at some point in their life.

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You’re not getting them as fresh as they are in an embryo, but pretty close. Are you able to get stem cells from the fat in the knee?

The issue is you’re getting stem cells from an adult that’s already of adult age.

There’s still some floating around in there.

Ideally, in theory, we’d like to have cells from a young individual with placental tissue.

Mine are old and decrepit and they’re obviously dropout stem cells because they didn’t bother to turn into something else by now.

With something like the placental stem cells, you’re generally getting them from a C-section. It’s tissue that would be generally discarded as medical waste to begin with, but you have a younger mother. Usually, ages 18 to late 20s is the optimum age. They essentially isolate the cells and they’re able to culture them in vitro and expand them out into larger cell lines that are capable of creating very large quantities of product that is, from a characterization standpoint, almost identical. There’s a variation from one woman’s placental cells to another. That’s the nature of biologics in general because it’s human-derived tissue. Even if you have the same process, you might end up with a slightly different composition of matter on the final product.

Do you think that there are supply constraints on this or is there plenty of placental stem cells?

There’s definitely some highly competitive market with human tissues in general. A lot of companies are getting exclusive contracts with the tissue procurers. There’re companies that their sole purpose is just to acquire birth tissue or organs, the whole organ market trade.

There might be some screwy incentives there. Do you think it’s possible this explains why there has been a massive uptick in the number of C-sections performed?

It’s not necessarily related to the organ market. The C-section issue is more of a convenience thing for the factory perspective where they’d like to get women in and out as fast as possible. There’s a huge amount of unnecessary C-sections. There’re some interesting books on the topic where they’ll push women into C-sections that are not medically necessary just because it’s faster.

That’s what I heard but maybe not because they’re trying to get more placenta.

There’re some laws in place regarding the sale of human organs. It’s done in a strange way where the mother of the child will give consent. Informed consent is one of the laws regarding human tissue acquisition. She has to sign. The way that they word it is, “I hereby donate my birth tissue for scientific research,” which is interesting because the way that’s worded you think it’s going to academia and you think it’s going to be, but a lot of this is going to for-profit mega-corporations.

They don’t realize that their one placenta is probably going to make hundreds of thousands to over $1 million with a product. It’s a little bit misleading and it’s a little unfair, in my opinion, that they can’t legally compensate them. There’s a lot of steps required, with, for example, the American Association of Tissue Banks. When you receive the tissue, there’s an entire process of handling. It has to be kept at a specific storage. Sometimes there’s a sealing rinse or sometimes they’ll use an antibiotic rinse because sometimes there’s a little bit of exposure to different types of microorganisms from the skin when they do the C-section.

Essentially, you want it as sterile as possible. You don’t want to introduce any sort of organisms into your cultures that you’re going to be using. With the exosomes, you’re culturing the stem cells for the explicit purpose of harvesting the exosomes and creating a cellular product. The final product is completely stem cell free, which is interesting. There’s been a lot of stem cell research. There are interesting therapeutic applications, but it’s with the gray market in the United States because there’s been a lot of adverse effects associated with the stem cells.

That’s why you see a lot of people flying to Mexico or flying to another country for stem cells themselves. The issue is they’re allogeneic, meaning they’re coming from another human being, in which they could have an immune response in you because they have MHC Class II cell surface markers that the body may recognize as antigen. “This is a foreign tissue. It does not belong to me. It’s an invader.” The same situation with organ transplants.

Sometimes the stem cells have transdifferentiated into the wrong type of tissue. For example, there was a scenario where a woman had some injected into her face. It migrated to her eye and transdifferentiated into osteocytes, which is bone. She ended up growing a chunk of bone in her eye. There was another, they were trying to cure paralysis in somebody with a spinal cord defect or spinal cord injury, a quadriplegic. The stem cell injection that they got overseas was from a bad line that turned into a large tumor mass that is extremely difficult to remove once it’s in the spinal cord. That’s a very serious area for surgery.

In that case, if the reason it became a tumor was because of the stem cells that were used, and that you used a different stem cell from a different donor, maybe you would have had a different outcome?

It’s possible it’s that the donor may have had a genetic defect. Sometimes when they mass culture these cells, they’ll do what’s called expansion, where the cells will divide and you’ll continuously divide them to additional passes. It’s called passaging. You’ll passage more and more, but after the cells have gone through this division stage through around 68 passages and beyond, that’s the point where you might get some genetic aberration.

As with humans, after 6 or 8 generations, your grandkids are total assholes. In that case, from what you’ve said, if I understand, if it had been stem cells derived from a fetus, there’d be less risk of this kind of genetic passing of a tumor through a stem cell to a new person.

It’s possible. I don’t have a whole lot of experience with fetal stem cells directly.

The other thing is if you inject me with stem cells in my cheek and it crawls up to my eye and creates a bone and that’s not what I intended, how are you supposed to be telling these stem cells what they’re supposed to transmogrify into?

That’s the interesting thing now is we aren’t quite at a place yet where we have full control. We inject into a site and we hope that it differentiates into what the neighboring cells are. The neighboring cells are releasing signaling molecules that will communicate and they know what they’re supposed to do. What they’re finding in research is that when people are getting these stem cell injections, initially, the mode of thinking was that, “When you get these injections, these live stem cells are ingrafting into the human and transdifferentiating into whatever tissue and exerting whatever the effects are that you’re aiming for.”

There have been some studies showing that large portions of live cells that are injected actually die off very quickly. They don’t survive in the host. The exosomes being released from the injected stem cells are actually inferring most of the effects that we’re seeing. With exosomes, we’re able to cut out this middleman or this other product that has all these issues. Another issue with stem cells is their lives. You have to transport them at cryogenic temperatures. You have to have a whole Coltrane shipping and storage versus exosomes which are off the shelf, stable, and can be kept at slightly warmer temperatures for shorter periods of time.

Let’s rewind here and explain what an exosome is. I don’t have a strong association with what an exosome is. Can you try and school me on that?

Exosomes are starting to gain a lot more attention in research because initially, the thought was that they were just waste molecules. What they are is a lipid vesicle membrane, which is a package that is produced within the cell that is released by the cell. It’s used for paracrine communication, which is cell-to-cell communicational travel to a different part of the body and exerts an effect there being, they’ll have uptake into that cell.

It’s like little bits of code and they contain different types of protein like micro mRNA, various anti-inflammatory and immunomodulatory cytokines, lipids, etc. There are growth factors and healing factors. The exosome itself is about 70 to 100 nanometers. They’re nanoparticles. It’s very interesting because they’re very small-sized and able to travel through the bloodstream, but interestingly they’re able to cross the blood-brain barrier.

You’re able to use them for a lot of conditions of the brain that have, for example, neural inflammation. We’re seeing in even something like depression, anxiety, PTSD, you have some level of neural inflammation. You can have inflammatory processes within the brain that creates this chicken and egg scenario where if you’re somebody with PTSD, severe panic attacks, or anxiety, and you have depression, you have these circuits wired for these types of thoughts. Those different unit hyperinflammatory state causes more symptoms, and the symptoms then cause more depression and anxiety, and it creates a feedback loop of continuing this cycle.

Inflammatory stages mean more blood is being sent to those tissues?

More blood and more active inflammatory cytokines.

What are cytokines?

Cytokines are signaling molecules.

Are they like exosomes?

Exosomes contain them and they also have various mRNA that codes for them.

An exosome contains cytokines, which contain mRNA.

We’re still elucidating exactly what the full characterization of it is because when you do a protein panel assay, you might see that there are hundreds of thousands of different compounds within an exosome. It depends because we’re focusing mainly on stem cell exosomes because that’s the therapeutic applications that we’re interested in. Most eukaryotic cells produce exosomes in some manner.

What does eukaryotic mean?

It’s cells that are from average animal or average plant, a lower life form.

An exosome is like a FedEx delivery driver. Cytokine is a package, and then mRNA is like a floppy disk inside.

Yes, the executing code that once it’s taken up by the cell becomes the blueprint to manufacture more proteins based on what that is in particular.

What I’m trying to understand is, do all cells have these exosomes that they spit out?

Most cells do, but they’re not all necessarily things that are therapeutics. One of the interesting things that they’re researching exosomes for is biomarkers for specific disease states. If you have a specific type of cancer and we find that a specific type of exosome is released by that cancer, they could be developing a diagnostic test. It’s very hard to diagnose certain types of cancer, especially if it’s an organ that’s very hard to get to. If we’re able to find that in the bloodstream and create diagnostic tests, it’s early preventative, finding diseases earlier, and being able to treat them earlier.

The other interesting application besides therapeutic use is drug delivery systems. We’re able to take these nanoparticles and there are different techniques that you can load them with a pharmaceutical drug. Since they have this targeting effect in vivo, you can use the exosomes to target a specific disease state. For example, you want to get a drug across the blood-brain barrier that normally cannot cross the blood-brain barrier. It can cross within the exosomes and now you can deliver a certain substance to the brain that you could not previously.

How does the targeting work?

Targeting is when you have a specific site of inflammation. If you have a highly inflammatory disorder, autoimmune disorders, osteoarthritis, various muscular-skeletal disorders, these sites are actively releasing inflammatory molecules. There’s a homing effect for exosomes where they’re able to target and find, within the body, where they’re supposed to be going. It’s pretty interesting.

Can you somehow program it to go where you want?

The interesting area now is synthetically engineered exosomes. Creating an exosome that has a specific purpose or specific indication, for example, there’s some outside of Israel. There’s a new one that they’re developing for COVID that is very specific to acute respiratory distress syndrome from COVID. It specifically targets the lungs and inflammation in the lungs. It’s had some very interesting results.

In terms of having a differentiated product that uses synthetic biology to create a very specific exosome that’s targeting a very specific indication, that’s very valuable. Anybody can open up a laboratory and start mass manufacturing exosomes that have a broad general use. Essentially, the way the market is structured right now is that it’s a very gray market, a lot of the Wild West frontier where doctors have the legal right to use products off label in a manner that they see fit for their practice.

It’s not illegal for them to purchase the product and, for example, inject that into the spine of somebody paralyzed but the companies that manufacture it absolutely cannot advertise it for that purpose. You can only advertise it for whatever the purpose is that they have FDA clearance for. If it’s for cosmetic use only, they can advertise it for cosmetic use only but that’s becoming a loophole now where they’re marketing it for cosmetic with a wink-wink nudge, and a lot of physicians are purchasing it and injecting it into the articular spaces for arthritis.

Is there any legitimate cosmetic use of injecting these stuff in people?

Cosmetic and legitimate are subjective.

Maybe like a bunch of exosomes in my lips for filler.

Possibly not your lips but like your skin, I haven’t seen highly conclusive data on this yet but some who have received this claim that the rejuvenation of the skin cells is causing the new skin to grow back with the texture of the baby skin. Very soft with very small pores and reduction in pore size. I personally have seen a patient that was injected that had very severe rosacea around his nasolabial folds. Very red and blotchy. Within about 48 hours, he had complete remission of the rosacea. It’s completely clear. It did return after a few months. It’s not a permanent fix because the underlying causative factor that’s causing that condition is ongoing. It’s not a permanent cure.

It was exosomes injected into that skin and it’s generic exosomes harvested from a placenta like you described before?

Yeah.

We’re at the beginning of figuring out all the places this could be used.

This is the thing that’s the most fascinating is, when you go into pharmaceutical or biopharmaceutical development, whether you’re a startup or whether you’re a multibillion-dollar corporate entity, they dump massive amounts of money. To the thousands of drug candidates, you might get a handful of drugs that end up making it through.

Some of them will make it through phase one clinical trials and then they won’t pass to phase two. A lot of us don’t pass it. Most of them never make it to market. It’s a very high-risk ratio of the cost of R&D and trying to get through the clinical trials to get it to the point where it’s perfect for humans, but then you have something like exosomes where you don’t have your one indication. There’s this massive variety of so many indications that we’re seeing efficacy for.

There’s a lot of rat studies that are fascinating and now we’re starting to see some human studies and case reports for human clinical trials. For example, post-stroke, if it’s administered immediately after stroke, there’s a very high chance of not having permanent brain damage from stroke if it’s a particular type of stroke or from a CTE from a brain injury.

This is only, so far, tested on strokes that rats have had?

I’ve seen some case studies in some hospitals where it’s being used with humans.

I’m low risk for stroke but I’m terrified of it. Can I get a bottle of exosomes and stick it in my backpack and whenever I have a stroke, just chug it? How close to that could we get where instead of an EpiPen?

Right now, the big issue is needing to be stored because the mRNA may be denatured at high temperatures. In general, you want to store it at around negative 80 Celsius.

I heard somewhere that the mRNA vaccines, I don’t know if it was both of them or one of them, are working out to be pretty effective stored at normal.

They have a shorter lifespan but they’re also working on what I’ve seen as layoff-alized versions, where it’s essentially a freeze-dried version that’s reconstituted. I haven’t seen a lot of shelf-life data on that yet, so I don’t know.

It’s too soon to know. How does mRNA work?

An mRNA or messenger RNA provides the translation of the RNA into the target cell where it will aid in the manufacture of the new proteins.

Can I think of mRNA like a system update like injecting some new code into a cell?

Yeah. It’s like a little floppy disk that’s hopping over there and has a little executable program.

If you extrapolate 100 years from now, imagine that we learn a lot about mRNA and we learn to write code.

That’s the holy grail of gene editing in general. There are so many incurable diseases right now. They are tinkering with congenital blindness and they’ve actually had some success where they were able to rewrite code that was for certain types of blindness.

The type that someone’s born with. It’s genetic and we’re rewriting the genetic part that made them.

The holy grail is, “Can we cure people that have congenital diseases by altering their DNA long-term?” There’s also CRISPR which is this great invention, but there is a concern about off-target effects. If you’re editing a certain gene sequence, there may be an unintended downstream edit somewhere else that comes with other unintended effects. We don’t fully know the long-term implications of stuff like that. That’s why you haven’t seen, “Here’s the blockbuster drug that was made with CRISPR.” It hasn’t happened yet.

This seems like a big data problem and over time, we’ll know more and more about what’s in that genome, what the different bits of code do, and we’ll be able to write it. We already know how to write it, so in some sense, if all that went well, which might take more or less than 100 years, maybe 1,000 years, who knows. At some point, though, we’ll probably be able to figure out what all the code is and we’ll be able to write any and all of it. We’ll be able to repair the code that’s damaged or causing things like congenital diseases to be passed on, and then we’ll be able to design radically new variants of humans.

This is where people start to get into ethical dilemmas because it’s like, “What is fair?”

I know that ethical dilemmas are not part of this discussion, though. We want to touch about what’s causing them.

I have a mad scientist approach to things. I’m very much a fan of tinkering. This is a little off topic but when I think about space exploration, there’s a lot of talk about, “Do we need to do gene editing in the future in Mars?” It happens, for example, where there are species of animals that are in sunlight all day long like elephants and dolphins, who don’t have high rates of cancer. It’s something about the compounds within their gray skin that they don’t have this crazy high rate of cancer that we humans have.

If we’re talking about putting people in space or sending them for long time, they’re getting bombarded by all the different types of cosmic radiation. What if there is some gene sequence in their skin that would allow humans to have some? This is just me guessing. There are a lot of interesting applications for space travel. With the radiation, you also have a lot of immune system suppression. That’s a big issue in space. Your immune system goes to shit.

mRNA is like a little floppy disc that contains an executable program for your body.

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That’s what we’ve seen with the astronaut with the twin brother. Ethical questions require a completely different conversation.

I try to stay out of that just because.

I do too but it’s not because they aren’t important.

It’s important but I also have a thing for the idea of experimenting a little bit on the edge because that’s how you make progress. You get a little bit outside of the boundary. You have some people push things a little too far. There’s no argument like with the Chinese CRISPR editing of the babies. Did they really need to be edited?

Can you describe that?

The Chinese scientists did some CRISPR editing of these babies to give them immunity against HIV. Arguably, is that really a concern? Number one, nobody’s doing CRISPR experiments on human babies. We don’t know the long-term effects or the downstream effects of this. What are the odds of these babies encountering HIV in their lifetime? Where do you draw the line? Do we start to edit for every single disease? To my knowledge, they weren’t coming from parents that were HIV infected.

If they could make all future humans HIV resistant, we could eradicate that disease.

Yeah, but I don’t think he started in monkeys or rats.

He wanted to get a name for himself.

My understanding is, it was ego-driven and he wanted to be a famous person. It’s interesting because I don’t have this fascination with the slightly not okay experiments of Russia and China. They do push the boundaries in a way that’s not acceptable here but it’s fascinating data.

I’m not endorsing any particular thing.

I’m not either. I just have curiosity.

We only want to know what’s possible. If you just imagine, we get to a point where we comprehensively understand all the code and the DNA. We understand how to program mRNA and do whatever we want, we eradicate all the diseases and we bolster immune systems. We get rid of all the things that can kill you. Do you think that would be a problem for evolution?

You’re cutting out the natural selection, which is another ethical dilemma. Everybody gets to live.

We cut out the survival of the fittest while keeping natural selection. You get to choose a mate.

Is that going to increase long term some defects? If you’re in a poor country, you need to have access to those gene editing technologies. If you’re in a third world country, are you going to have access that the other people in the first world countries have?

I don’t think we’ll have third world countries much longer.

You don’t think so? I don’t know. When I visit these, I still see how far behind they are. Automation will come and we’re hoping that these menial labor tasks such as the cruel labors ideally will be replaced by robots and hopefully get these people into better and maybe universal.

A lesser form of humans that we can create with our genetic superpowers to do our bidding. Biological robots. No conscience, clean my clothes, bad idea. I am just kidding.

I have a fascination with the idea of growing brain organelles which you can grow these mini-brains from neural tissue. The question right now is, do they have consciousness? Are they suffering? We don’t know.

Do we grow them and put them in geckos? I would love to have a gecko that could braid hair.

They’ve done something interesting. I saw a pig and a human brain chimera. There were some monkeys that they had mixed with some human genes.

That does have a bit of a creepy feeling.

If we give a monkey some aspects of human consciousness, are they suffering? We don’t really know, but what if we’re able to grow this organelle, place it into a computer system. If we can use the computational power of a brain versus a computer, obviously, it’s two very different styles. If you look at the way that memory in the brain works, the millions of various neural connections between so many disparate areas of the brain and different memories and recall the way that we process things. When you’re heading in the direction of artificial general intelligence, I don’t think they’re ever going to replicate that purely in silico. The hybridization of human neural tissue like tissue on a chip or brain-computer interface with an actual neural brain, that’s the area I’m interested in.

If that works, maybe we can make a big one. The human brain is pretty big but what if we could make a 40-pound brain?

That’d be cool.

We could modify humans to have thinner skulls, more brain, that seems like it would have an effect. Maybe there’s some point of diminishing returns where the circumference of the brain is too high but we could hybridize the architecture and take these multi-core chip architectures and have multiple brains with high-speed interconnects.

We have them get into the whole BCI Neuralink area. Can we master the understanding of electrical and data transfer? We’ve had a little bit of progress. If you see, for example, people that were born blind, they were able to bypass the optic nerves and able to put cameras on these people’s heads that send rudimentary images into the visual cortex of the brain and they’re able to see. They don’t see 20/20 like us but they can see light, dark areas, navigate within their homes, find their way, and see the outline of contrasty things.

You see that now with hearing. You’re seeing the hearing implants that they’re bypassing the defective cochlear structures and able to implant it directly into the auditory portions of the brain and they’re able to hear. I see all these senses that are now being able to be augmented or completely replaced in people that are born without them. It’s like, “How far can this go? Can this go to the point where we can plug in computers and then start to use it with the neural language?”

Neuralink is not the first or the end all be all. The people in the neurotech community have been working on BCIs for decades before Neuralink. If you go into the NeuroTechX Communities, they’ve been working on this forever and it seems the spotlight was stolen from them because they have been working on this for years.

There’s probably a story just like in electric cars and spaceships too. When we think about computers, the computers have a bus. They have an interface. You don’t try to tap into every transistor in a chip. You have a bus where the chip does this processing and then there’s like an I/O bus where you can move data in and out.

You might think of it like the eyeballs or the spine is I/O for the brain. I’m making shit up here but I’m guessing there’s a lot more to be gained in the short run by trying to understand those interfaces and use them than to try and go tap into and monitor every neuron in the brain. Even Neuralink has no concept of how to get there.

It’s very much in the stages of infancy. It’s very early days. I like where it’s going and that the initial use cases are going to be for people with quadriplegia or people who have locked-in syndrome that cannot communicate outside, they have no method of communication whatsoever with the outside world. With BCI, they’re going to be able to have some life skills where they can communicate on a computer. They might be able to drive their wheelchairs around their house even though they’re completely paralyzed. They can have some basic living functions, which are really special.

In some sense, it’s a way to circumvent the ethical questions about the work because we look at them and say, “These people got less than the average human. There doesn’t seem to be any ethical concern about trying to close that gap for them.” That’s also a little bit presumptuous to say. I don’t know. Maybe somebody knows but if you have Down syndrome, who’s to say? They seem pretty happy a lot of the time. Maybe they don’t want to be like us. I don’t know. I’m just making that up.

We do seem to circumvent the ethical discussion out, whereas if you’re talking about making humans that are advanced on some access beyond what we’ve seen, then it gets sketchy. I imagine a near future where the NBA is entirely populated with super tall, blond Chinese people because they’re smarter than us and are way better at math. I see that coming because they have a different ethical sensibility in that region. We have been very conservative about gene editing.

We’re going to see a lot of the innovative stuff in the countries that have slightly more lax regulatory controls on what they’re able to do and not able to do. I see the double-edged sword on this because if you went back to look at some of the unethical experiments a few decades ago, they did some pretty wild stuff. In other countries, too, they did some pretty wild experiments.

There was one where they were attempting to cross hybridize women with sperm from a specific chimpanzee or some type of monkey and it was very unsuccessful. I don’t think any of them fertilized or any of the embryos made it but you can never get away with that now. It’s so wild but at the same time to me, that’s fascinating because what if it works?

What is ketamine?

It’s a dissociative anesthetic.

I know there are different classes of drugs, and that’s one of them. What are examples of classes of drugs? What does dissociated mean? What does anesthetic mean?

With anesthetics, you have more typical inhaling gas. When you do surgery, they’ll often intubate somebody. They’ll have an anesthesiologist that will control the levels of the gas and sometimes there’ll be a paralytic agent where their body is paralyzed. They’re not experiencing pain and they’re not conscious.

Ketamine is a fascinating dissociative anesthetic for many reasons. It’s on the World Health Organization’s top ten most essential drugs because it does not require an anesthesiologist to be present to monitor it. It completely spares the respiratory system. You don’t have a risk of suffocation. This is something that’s still used in American hospitals, mainly for pediatrics, and now off-label for pain and depression, on battlefields or third world countries where they don’t have the resources to have a full-time anesthesiologist. They’re doing field surgery, and a lot of third world countries are just doing quick surgeries that are subpar, it’s a very critical drug for that.