
Sign up to save your podcasts
Or
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.
Stem Cells: Donating birth tissue for scientific research doesn’t go to academia for research but to for-profit mega-corporations.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.
TweetYou’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.
Stem Cells: Some recent studies show that a large portion of live cells injected die off very quickly. It’s the exosomes being released from the injected stem cells that infer the effects that you experience.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.
TweetThat’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.
It’s regained a lot of interest over the years because it has a very fascinating efficacy rate for depression, especially suicidal ideation. It is far more statistically effective than typical SSRI antidepressants, especially for people that have suicidal ideation. People that are suicidal, within 45 minutes of infusion, are no longer suicidal.
The main reason it was removed from main use in hospitals is it does have a psychedelic, disorienting, or dissociative effect when people start to awaken from the anesthesia. It can be very psychedelic and scary for them. It’s used mainly in pediatrics and in people with asthma or with other respiratory system issues. With depression, there’s so much overwhelming evidence. Ketamine has been off-label for patent for many years. It’s generic and a very cheap drug. It’s something like $10 for a vial of it. They’re reselling that for thousands. Cash pay for these ketamine clinics, one of the major companies, SPRAVATO, which is the S enantiomer of ketamine versus the racemic which is the normal RNS.
What’s the difference and what does that mean?
With the manufacture of drugs, you have something that’s called stereoisomers, which is basically you have the same bonding configuration of the molecules, and you have what’s a left-handed and right-handed version. It’s still the exact same young compound but in 3D space, they might be bent in one direction. You have receptor sites in your brain, for example, NMDA receptors for ketamine, and the left glove might not necessarily bind as tightly to the specific receptor site. It might confer slightly different effects.
With ketamine, you have the R-isomer, which supposedly has more of the drunken kind of stupor high feelings, and then you have the S-isomer, which is used medically in Europe that can be a little bit more psychedelic and it seems to be lacking in the physical drunkenness components. Regardless, the SPRAVATO, which is being used very for PTSD in veteran’s hospitals. When you get that administered, they make you wait three hours before you’re allowed to leave. You’re not allowed to drive.
Stem Cells: The brain has millions of various neuro connections. It is extremely difficult to replicate such a complex system in artificial intelligence.They want to make sure you don’t have some weird psychedelic side effects.
It’s a fairly low dosage nasal spray compared to the IV bolus or the IV infusion. It’s interesting to see it’s not just depression, but it’s also pain. They’re finding a lot of pain relief, neuropathic pain, especially, with ketamine. We used to think that it was just NMDA receptor antagonism, but now we’re finding that there’s a multitude of other possible mechanisms of action. There’s quite a variety of possible reasons why it is so effective for depression.
The main downside is it has the potential to be highly addictive. It is something that does have addiction potential. The relief of depression is so intense that people who have severe depression start to chase that relief of depression to the point where they can become addicted. If you’re not receiving psychotherapy, in addition, if you’re just getting straight-up infusions with no psychotherapy in conjunction, you’re not making any long-lasting changes.
It’s not covered by insurance, so it’s a cash payment. In a major city like Manhattan, you might be paying $600, $800, $1,000 per infusion. It’s not cheap. It’s not covered by insurance yet. It should be cheap because the actual product itself is something around $10 for a generic vial. It’s not expensive. There’s massive markup, and there’s a gold rush of these ketamine clinics just because they’re very easy to open.
What are they doing, mostly? Suicide prevention?
That and pain for chronic pain patients and then chronic depression patients, it’s done in a very sterile doctor’s office that’s not conducive to something that has a slight psychedelic element. You’re in a brightly, fluorescent lit room.
What would be better?
In my opinion, is the use of virtual reality as an adjunct, which is what I’ve been studying. I completed an eighteen-patient pilot study clinical trial. With that, you have an additional layer of immersion. It’s interesting, especially with pain patients where the objective is you would like to get these people off of opiates. We do not want people to do opiates. It’s a dangerous route to go down because then you can’t get off of them. With something like VR, you have what’s called immersive distraction, where you have a finite amount of processing power in your brain for all your senses.
If you’re experiencing greater high levels of pain but then I expose you to high levels of visuals and I expose you to sound, there might be a physical component. Some people are adding in a sub-pack which is like a subwoofer vibrating vest. There are all different things. The more sensory stimuli that you’re putting in, especially if they’re watching something with some emotional component, your brain cannot process the pain, the visual, and the auditory.
They’ve been doing studies on this and finding that VR alone is reducing the perception of pain. This is something that’s very important for people with severe burn injuries who have burned and lost 50% of their skin. It is excruciatingly painful to do the wound changes. They don’t have skin. It’s completely burned off. They’re finding that with the use of VR, they’re able to tolerate a lower level of opiate painkillers. They have less fear and anxiety built up about the wound dressing changes because they know that they’re going to be distracted. They’re not seeing what’s going on, and you’re not paying as much attention and they’re occupied mentally.
There’re also some other use cases for VR. They did a study with twelve paralyzed patients that they were able to show in VR, there’s this very interesting phenomenon where if you show the paralyzed limbs moving and the physical therapists move the limbs, you start to regenerate neural growth where they were able to regain motor function in parts of the body that were previously paralyzed. It’s a fascinating study if you google it.
It goes to show that the effect of VR has on the brain alone is very powerful because it’s so immersive that it can be nearly indistinguishable for the brain from a real experience. You see people on the edge of a cliff in VR and consciously, you’re safe, you’re in your house. There’s no hole in your floor. People, as soon as they approach that hole, they lose their balance and fall.
In the Oculus with the plank simulator, everyone should try it. It’s insane because you can have that exact feeling.
People fall. It’s hilarious.
They do. I put my dad in it. He would not step off the plank-like, “Nope. Not doing it.”
It preys on people’s fear of heights and be falling. It’s like your carpeted house is part of the brain that it does not accept.
The one that fascinates me the most, I don’t know anything about it, but I heard about a project where Navy SEALS or something, were using VR to treat PTSD. 100% of Navy SEALS have PTSD. It’s part of the job. I don’t know anything about this stuff. I’m making this part up, but in what I learned about trauma before, it seems to me that a lot of cases of PTSD where you get yanked out of a situation before your brain got to finish a story.
Your brain gets stuck in this cycle of trying to find an ending for the story that never got finished. You’re stuck in that spin cycle. With VR, what they’re doing is they’ll put you back on the battlefield where your buddy got shot or whatever. You’re there and you get a chance to finish the story. I’m making that part up. I honestly don’t know what they do. I made all that up but maybe it’s something like that.
From what I’ve seen, one of the issues with mass adoption and mass scaling of that is PTSD is personalized visually, which means some 3D designer has to rebuild like, “Was there an exact incident in Afghanistan where this is what happened?” The next person might have had a completely different experience. They have to rebuild. It makes it a little bit more expensive and harder but it seems to be effective because through this therapy, they can relive the situation, and they realize that they’re safe now and they’re not in the war zone.
With the right kind of therapist, they’re able to revisit these emotions. There seems to be a pretty good high rate of treatment for this and PTSD. The circuitry in the brain is rewiring to create hypervigilance, which is you’re in a state of constant anxiety, you’re sensitive to sounds, and sensitive emotional triggers. It’s sad because it’s such a massive issue in the United States, PTSD with veterans. They’re not doing a whole lot to treat them. It’s an area that they deserve to have a lot more options for therapy.
Fully understanding how mRNA works is the Holy Grail of curing people with congenital diseases by long-term altering their DNA.
TweetI have a friend who’s a pediatric doctor and he wants to use or has used, I don’t know what the status of it is, virtual reality and ketamine with kids who have a variety of different problems to help them adjust. It seems like a frontier.
I’m working with virtuality with ketamine. I would like to see data on the long-term safety of any type of psychedelic on a child. Some of the early research that I did when I was a teenager was on psychedelics on the developing brain. Your brain is still developing up until you’re about your early twenties. You’re not fully formed. The question is, “Are we causing any long-term damage to a developing brain by exposing them to psychoactive substances at a young age?”
Some of the data that I produced seems to suggest that there might be long-term effects. I focused on cognitive development in adolescent rats with a substance called the five immunity IPT, which is a tryptamine psychedelic drug. We did find some minor deficits in spatial navigation and flexibility in learning related to the serotonergic pathways in the brain that are associated with memory and flexibility learning and it wasn’t massively drastic.
These rats probably weren’t going to have a good time without MapQuest or GPS. Now there are some data coming out saying that teenagers that smoke marijuana may have some brain issues later in life from smoking early. I have mixed feelings on the whole idea of psychoactive for children. Although I’ve seen some interesting case studies that some of them were not published for fear of legal reasons. There were some children that were semi-autistic, born mute, and could not speak English.
There was a story that I had heard from somebody reputable where the family was associated with some major hippie touring bands of the 1960s and the child accidentally got a piece of candy that had lysergic acid diethylamide, LSD. The parents freaked out. They’re like, “We don’t want to go to jail.” Shortly after the incident, the child began to become verbal.
It’s interesting now because, in the past few years, the major breakthrough is we now have FMRI studies of brains on LSD. We’re seeing the hyper-connectivity between parts of the brain that were not connected. We’re seeing different parts of the default network that are cut off. It’s was a totally different operation of the brain. Now they’re even suggesting psychedelic psilocybin mushrooms for patients that are in a vegetative state. They think that because it does regenerate neural tissue, can we wake them up out of the vegetative state? That’s interesting.
Would it be amazing if we figured out that anyone can be brought out of a coma?
It’s possible with people with brain damage. We see with neuroplasticity that some people that have had a traumatic brain injury, even though that part of the brain has become as ischemic and died, they’re now seeing with DMT, LSD, psilocybin that they’re able to regrow new neural connections. The brain has fascinating neuroplasticity because it’s able to remap. Once you’ve lost some important part from brain damage, you can often remap to a different location. You get some interesting results.
It goes against the old school of all the neurons that you’re ever born with and they die over time because you drink alcohol and you do this and that. Now they’re starting to say that maybe that’s not true. It seems like we are still regenerating. There are stem cells in the brain. From what I read, alcohol is not particularly kind to your neuro stem cells that you do have present. Personally, alcohol is a toxin that should be moderated upon. It’s been around for millennia.
Its effects are at least well accepted. I don’t drink at all.
We’ve seen people live to 120 years old who drink a glass of whiskey a day.
I learned that in junior high. Alcohol kills brain cells. I figured I might as well keep as many as I can. I never started.
It’s an interesting social lubricant. You’ve seen it in Greek times and ancient times. It’s ubiquitous through all stages of human culture, some sort of fermented alcohol. It’s not a drug per se. It’s a toxin. You’re poisoning yourself. The effects that you’re feeling are the effects of being poisoned. It’s interesting to see how much of the brain is generative and neuroplastic.
Looping back to exosomes, now that we can get them through the blood-brain barrier, some of the damage is being caused by stroke or by exposure to chemicals or by various brain injuries or drug use. There’s a high probability that there might be between psychoactive substances like psilocybin mushrooms for example and between stuff like exosomes that are showing efficacy for treatment of post-stroke and all these other neurodegenerative conditions. There’s some possibility on the horizon of being able to repair some level of brain damage. Who knows? Maybe stave off dementia or have some treatment for dementia. I’m interested to see how far this goes.
What do you think the near-term priorities for exosome research should be?
There are many different areas.
Whatever it is, there can’t be enough.
It’s connecting back to what I was mentioning earlier with the big pharma companies that have their one-hit-wonder drug that does the one thing and they poured their billions of dollars of research. If they fail the clinical trial, it’s garbage unless they can repurpose that.
Can exosomes cure erectile dysfunction? They then could get all the funding they need.
There are people who claim that it does. I haven’t seen solid research on it. There are clinics advertising this. There’s this little gray market going on. The FDA, their stance on it is what they call selective enforcement where they’ve agreed to look the other way as long as the companies are not manufacturing it and marketing it explicitly for injection. That’s not legal. A drug is injected. They’re marketing it for topical use. The doctors legally have the right to use it off-label for whatever they would like.
Is there any topical use of exosomes that does anything?
With the cosmetic clinics, there are all these interesting Vampire Facial procedures, post-laser resurfacing microdermabrasion mixing it with PRP. They use it for hair-loss.
What’s PRP?
Platelet-rich plasma. You’re essentially extracting from your own blood and then it’s being returned to you. It’s being ultracentrifuged and returned to you and injected back into you. You’re back to the scenario of your old cells and you’re giving your old cells back to you. From what I understand, the PRP makes scaffolding.
In Korea, they already have a multibillion-dollar exosome company. Korea’s skincare industries are massive. Most women have plastic surgery at a young age. I was talking to some of my female Korean friends. It’s normal for your parents to pay for a nose job and eyelid surgery. You’re expected to have flawless skin. It’s a massive beauty industry there.
In the United States, we have a big regenerative anti-aging market where a lot of people would like to live forever, lifespan extensions. It’s getting into is it pseudoscience or not? If people have the money to play around with that kind of stuff, I don’t see the issue. It’s one of the only substances that I’ve seen working in pharmaceutics that does not seem to have a detrimental side effect that I’ve seen.
If you look at something like Tylenol, which has a massive amount of overdoses, a massive amount of liver damage, all kinds of side effects. You have something like the exosomes, there are not many reports with the exception of a few unscrupulous labs that are selling contaminated products out of the warehouse, basement, or whatever. That’s why the FDA does need to step in and regulate a little bit better because those are the people that mess it up for everybody.
Stem Cells: VR alone is reducing the perception of pain, which is useful for people with severe burning dreams.It’s relatively safe to try different things with this stuff, it sounds like.
We have not seen off-target or downstream effects thus far. I’m not saying that there isn’t.
People should be allowed to try it. We have enough extra humans anyway. Some of them can be devoted to exosome research of their own volition.
I was one of the first guinea pigs. I had myotonic synovitis and my wrist was 99% cured. For that, I had five CCs of an exosome and saline preparation that was injected into the carpal tunnel. I had severe inflammation of my tendon from repetitive stress injury from poor risk posture when typing for my entire life.
In the past 5, 7 years or so of grad school, it became excruciating. The nerve pain that was shooting up my elbow made it unbearable for me to use a cell phone, to type, or to use a computer mouse. I ended up having the product injected into my wrist and I started feeling improvement that was not placebo within a few days.
Eventually, it’s been several years now and the pain is 99.9% gone. It’s what converted me over like, “This is a real product.” It removed the inflammation. Hand surgeons were saying, “There’s nothing we can do about it. We can inject corticosteroids into it.” It’s not a long-term solution of steroids injected into anything, atrophy muscle and the atrophy tissue. It depresses the immune system. Steroids are not a good thing.
I was at my wit’s end because I had gone to multiple top hand surgeons in Miami and they’re all telling you, “It’s not carpal tunnel syndrome. There’s nothing we can do about it. We can’t do the carpal tunnel release surgery because you don’t have a carpal tunnel.” What do I do now? I’m learning how to type with my left hand. I’m flipping over my brain. Finally, I was like, “I’ll try it. Why not?” It was life-changing for me.
I haven’t had an IV yet. It’s something possibly on the horizon. If I do get COVID, I want to get an exosome treatment because we’re seeing now there’s some IND, Investigational New Drug Applications, with the FDA. We’re seeing a lot of the detrimental symptoms of COVID is not so much from the virus itself but it’s from the immune system going hyperdrive. Your body is starting to attack its tissues in response to the viral infection.
Oftentimes, the viral infection clears out but your organs are still being attacked and attacked. This cytokine storm of inflammatory molecules thinks that it’s being helpful by continuing to attack the tissue where the virus was initially. That’s where you end up with multi-organ system damage. We’re seeing brain inflammation where people are starting to see hallucinations. It’s almost schizophrenia. These are people with zero mental histories of anything. You’re seeing young people with kidney damage, lung damage, and repetitious pneumonia.
You’re thinking that it might be possible to inject somebody with exosomes who had COVID and it might reduce the possibility of this cytokine storm?
Yes. It seems like for the subset of people who are experiencing the cytokine storm, there are some case studies and there are a few hospitals that are already incorporating it. There are a few controlled trials that are underway. There are certainly some companies submitting INDs. Not necessarily exosomes but there are a few stem cell companies submitting that are already in early clinical trials. With a lot of the use cases for stem cells, it’s fair to say that stem cell exosomes are possibly efficacious for some of the same indications. With a safety profile and better ease of use, you can transport it much easier. You can throw it in the freezer. You don’t have to worry about frosting live cells. They’re not alive.
I’m excited about what I learned about all this from you. That’s cool. I learned a lot.
There’s so much more. This goes on and on. It’s fascinating because it’s one of the only biopharmaceutical drugs that almost has an infinite possibility of indication and formats. You can have nasal sprays. You can have injections. You can have a transdermal patch that contains a skin permeability compound like DSMO that allows it to be absorbed through the skin into a joint without having to have needles. There are many interesting applications.
I can’t wait to have a problem so I can get some.
You can hop into one of those life expansion clinics on the West Coast.
Get some exosomes.
That’s the hot tricky thing right now for some of the people that are into lifespan extension and biohacking. There’s doesn’t seem to be a negative side effect profile thus far that we know of. There’s a small chance that if you have some hidden cancer tumor that you’re unaware of, it’s possible it could increase the growth in some manner through additional angiogenesis. Also, additional acceleration of biomass, it’s something that we don’t know for sure. There are people that are on the opposite side of it. They say, “No. It’s efficacious against tumors.” We need to see more data on that.
It’s a frontier. Do you have any questions for me?
Probably a lot.
I’ve been picking your brain.
There’s a lot in your brain to pick.
Now is the chance. You can ask the most incriminating questions you can think of.
Sometimes, you have to go beyond your boundaries to make actual progress.
TweetDon’t challenge me to that. Is that within the topic of healthcare?
Anything. I don’t care. It doesn’t matter.
Are you becoming more involved in the healthcare space?
No.
You’re mostly in the application of technology to solving more global problems.
Exactly. I want to try to close that gap. What it comes down to is you have to understand the problems. A lot of times, the people who understand the problems are so deep in it that they don’t also have the capacity to learn about the whole world of possible technologies that could affect the problem. It’s almost always true. On the other side, you have people who know a lot about technology. They’re specialists in something, but they don’t understand the problems that they might be able to affect. They’re often far removed.
As an inventor, I was always trying to escalate my knowledge on both sides, know more about what technologies exist and are coming, and know more about what problems exist in the world. Even if I can’t become an expert in them, I want to know the people who are. That way, sometimes you can match them up. All the time now, I’m trying to fill my head with what problems can I learn about and different industries, regions, people, and get a sense of them. Even if I can’t fully understand them, I can learn more about them.
On the other side, for me, it was computers. I wanted to learn everything I could about what’s not just everything about computers but what’s possible with them and try to understand where they could go and try to take them to new places. I’ve been making that my whole career. In some sense, we’re still at the beginning.
Computers have been super powerful. Outside of computers, where I know a lot less. There are also these amazing frontiers like gene editing, exosomes that I have no idea about, and material science. There are all different areas where you get this progression from scientific discovery. It gives you a sense of how things work.
From there, you can advance on, “What’s technically possible?” That’s where you’re taking the output of scientific discovery and trying to figure it out. It’s almost independent of whether it’s a good idea or not. What’s technically possible? I like to be in that space. What could we do with the knowledge we’ve attained? Every day, you get new scientific discoveries. There’s a new sensor, a new algorithm, a new paper on how something works.
To me, that’s input and I want to know so that I can match them up. There’s probably a real sharp limit on how many things I’m going to affect but that’s part of why I like sharing these conversations on the podcasts because then other people can learn those things, too. I’m learning them but maybe somebody who’s going to be useful at advancing exosomes will listen to this and get excited about it. Probably, I won’t be that one but somebody else could be. A lot of people don’t get the chance to come and hang out with you and pick your brain.
For me, what’s exciting is it’s a much longer path than a traditional path of being a specialist in one field. I like trying to learn a lot in disparate industries and fields and trying to see what the crossover is between these disparate industries. You have science and technology. You have something like art or architecture. How can you combine these different areas? You have AI and then you have molecular drug design. You have something else. I like seeing the crossover of it. It’s things that if you don’t have a background in multiple fields, you’re never going to come up with these ideas of cross-pollination.
There’s a real value in having depth in something. I meet a lot of generalists who haven’t done that. That erodes their ability to create a sense of perspective with all the new things. If you explore different areas and you’re trying to learn about different things, you need to be able to connect it to something. If the thing you’re connecting it to is deep, then you could have an effect. When you look at the invention work that I was involved in, all of our inventions are at the borders of different areas in science and technology. Have you read Consilience, E.O. Wilson’s book on this?
No.
You probably heard E.O. Wilson. He was a badass in science. He wrote this amazing book. I don’t know if he’s still alive. He was pretty old at the time. The book was trying to show scientists that these artificial constructs of chemistry, biology, physics and mathematics. It’s all science.
They all interconnect.
Those silos are keeping us from advancing. Nobody’s contributed more science than E.O. Wilson, so no one can argue with him. It’s pretty amazing. That’s a good one.
For me, my hope for the future is I want to learn quite a bit in one field and then move to the next field and move to the next field.
Life extension is going to become necessary for you.
I see that there are connections that people are missing. You need specialists. You must have expert specialists. You also must have people that are more generalist because they can see where all the different areas connect. You have your specialists who have the expertise in those fields. If you can see the bigger picture, you can see connections that other people can’t make. That’s where the new innovations are going to be coming from. It’s this cross-pollination of all of these. These fields are advancing fast right now. It’s exponential. Compared to when I started my Doctorate versus what I see now, I can’t even keep up.
No one can.
I’m trying to keep up with multiple fields of science. The papers that come out every day are mind-blowing. Some of this stuff is amazing.
It’s exciting.
I love it.
The tools are better than ever.
The tech is getting amazing. Even in biotech, we’re getting further and further down into nanoparticles, nanoparticle medicines. Regenerative medicines are getting more and more of synthetic biology and gene editing. It’s going in all these directions that when I started this journey as a child. It’s sci-fi coming real.
It’s amazing. My entire life has been characterized by the fact that I got a computer early on at a young age, and I stayed ahead of people because I stuck with it. You got into the next frontier, which is all that’s possible with genetics and with the future of biology. Now, we’re advancing that because we have computers, essentially. It’s too late for me to get into that. You got in on the beginning of it.
I don’t think you’re too late, though.
The world doesn’t need me for that.
Even with me in the beginning, I still feel like I need to catch up with people. My little insecurity being a generalist is I know I’m never going to have the depth that a specialist has, and I’m happy with that. I want to have generalists. I go as deep as I can. I don’t go to shallow level. It means that for someone that finishes their PhD and their one specialty, whereas I already finished my Doctorate and I’m still going deep on my own personal time.
The next thing is like, “No. It’s going to take me an extra 10 or 20 years to reach the level where I can start to see how are all these different things going to connect and how I can innovate and create something that all the specialists we’re not going to be able to meet?” It’s a little frustrating. This is a longer-term timeframe.
Some people have to be looking out of the box bigger. I’m not necessarily saying that I will innovate or create something, but it’s a possibility if they continue. A lot of people should try to learn multiple areas if they’re able to and motivated. That’s where the best innovations are going to come from, especially now that we can apply all this new technology to other healthcare principles to biotech principles. It’s such an exciting time. The equipment that is coming out is so advanced, and it’s fascinating.
Stem Cells: Oftentimes, the viral infection clears out, but your organs are still just being attacked and damaged.If I have a stem cell in a microscope and I put it next to an eyeball cell or some other cell, can I watch it transform into that on time-lapse? Is that something that someone can observe?
I suppose you could set up a time-lapse camera and see it.
How long does it take for a stem cell to turn into a skin cell or some other kind of program?
Something that’s often done with most stem cells is they’ll do a differentiation test where they will add a certain compound to ensure that it will turn into chondrocytes or adipocytes, which is the bone, the cartilage, and the fat. Osteoblasts chondrocytes, that’s a characterization confirmation to see if it indeed is undifferentiated.
Also, take one and test it to make sure it’s good.
Yes. In theory, you could set up a time-lapse camera and watch it. I’ve never tried it.
I’m going to look on YouTube. There’s got to be one.
I’ve played with microscopy of stem cells. They’re fun to look at. When you have a beautiful cell culture, they grow in a swirl form. It almost looks like art. If you print it and put it on your wall, they look so beautiful.
That should be your art project. Thanks for doing this.
Thanks for having me. It’s an honor.
People are going to love it.
I hope so.
This is an amazing conversation to share. The best ones are when you do more of the talking than me. We got a lot out of you. Thanks.
Thank you.
Important Links:Dr. Melissa C. Selinger, Pharm.D
Scientist, #MeToo survivor, former biotech exec/founding team, tech artist
ssd.jpl.nasa.gov/sbdb.cgi?sstr=21744+Meliselinger
NASA minor planet 21744 Meliselinger (1999 RF168)
Published neuropsychopharmacology research
https://www.researchgate.net/scientific-contributions/Melissa-C-Selinger-31520206
Upcoming researchKVR
Idea conception for and first author for KVR: A novel pilot virtual reality adjunct therapy for intravenous ketamine infusion for pain and depression in 18 patients, collab with Hamilton Morris
Journal publication TBA
Early KVR media coveragehttps://www.practicalpainmanagement.com/patient/virtual-reality-for-pain-depression
https://www.freethink.com/articles/virtual-reality-ketamine-therapy
Recorded on March 7, 2021The post Exosomes, Stem Cells, Ketamine & VR — Dr. Melissa Selinger appeared first on .
5
1919 ratings
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.
Stem Cells: Donating birth tissue for scientific research doesn’t go to academia for research but to for-profit mega-corporations.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.
TweetYou’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.
Stem Cells: Some recent studies show that a large portion of live cells injected die off very quickly. It’s the exosomes being released from the injected stem cells that infer the effects that you experience.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.
TweetThat’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.
It’s regained a lot of interest over the years because it has a very fascinating efficacy rate for depression, especially suicidal ideation. It is far more statistically effective than typical SSRI antidepressants, especially for people that have suicidal ideation. People that are suicidal, within 45 minutes of infusion, are no longer suicidal.
The main reason it was removed from main use in hospitals is it does have a psychedelic, disorienting, or dissociative effect when people start to awaken from the anesthesia. It can be very psychedelic and scary for them. It’s used mainly in pediatrics and in people with asthma or with other respiratory system issues. With depression, there’s so much overwhelming evidence. Ketamine has been off-label for patent for many years. It’s generic and a very cheap drug. It’s something like $10 for a vial of it. They’re reselling that for thousands. Cash pay for these ketamine clinics, one of the major companies, SPRAVATO, which is the S enantiomer of ketamine versus the racemic which is the normal RNS.
What’s the difference and what does that mean?
With the manufacture of drugs, you have something that’s called stereoisomers, which is basically you have the same bonding configuration of the molecules, and you have what’s a left-handed and right-handed version. It’s still the exact same young compound but in 3D space, they might be bent in one direction. You have receptor sites in your brain, for example, NMDA receptors for ketamine, and the left glove might not necessarily bind as tightly to the specific receptor site. It might confer slightly different effects.
With ketamine, you have the R-isomer, which supposedly has more of the drunken kind of stupor high feelings, and then you have the S-isomer, which is used medically in Europe that can be a little bit more psychedelic and it seems to be lacking in the physical drunkenness components. Regardless, the SPRAVATO, which is being used very for PTSD in veteran’s hospitals. When you get that administered, they make you wait three hours before you’re allowed to leave. You’re not allowed to drive.
Stem Cells: The brain has millions of various neuro connections. It is extremely difficult to replicate such a complex system in artificial intelligence.They want to make sure you don’t have some weird psychedelic side effects.
It’s a fairly low dosage nasal spray compared to the IV bolus or the IV infusion. It’s interesting to see it’s not just depression, but it’s also pain. They’re finding a lot of pain relief, neuropathic pain, especially, with ketamine. We used to think that it was just NMDA receptor antagonism, but now we’re finding that there’s a multitude of other possible mechanisms of action. There’s quite a variety of possible reasons why it is so effective for depression.
The main downside is it has the potential to be highly addictive. It is something that does have addiction potential. The relief of depression is so intense that people who have severe depression start to chase that relief of depression to the point where they can become addicted. If you’re not receiving psychotherapy, in addition, if you’re just getting straight-up infusions with no psychotherapy in conjunction, you’re not making any long-lasting changes.
It’s not covered by insurance, so it’s a cash payment. In a major city like Manhattan, you might be paying $600, $800, $1,000 per infusion. It’s not cheap. It’s not covered by insurance yet. It should be cheap because the actual product itself is something around $10 for a generic vial. It’s not expensive. There’s massive markup, and there’s a gold rush of these ketamine clinics just because they’re very easy to open.
What are they doing, mostly? Suicide prevention?
That and pain for chronic pain patients and then chronic depression patients, it’s done in a very sterile doctor’s office that’s not conducive to something that has a slight psychedelic element. You’re in a brightly, fluorescent lit room.
What would be better?
In my opinion, is the use of virtual reality as an adjunct, which is what I’ve been studying. I completed an eighteen-patient pilot study clinical trial. With that, you have an additional layer of immersion. It’s interesting, especially with pain patients where the objective is you would like to get these people off of opiates. We do not want people to do opiates. It’s a dangerous route to go down because then you can’t get off of them. With something like VR, you have what’s called immersive distraction, where you have a finite amount of processing power in your brain for all your senses.
If you’re experiencing greater high levels of pain but then I expose you to high levels of visuals and I expose you to sound, there might be a physical component. Some people are adding in a sub-pack which is like a subwoofer vibrating vest. There are all different things. The more sensory stimuli that you’re putting in, especially if they’re watching something with some emotional component, your brain cannot process the pain, the visual, and the auditory.
They’ve been doing studies on this and finding that VR alone is reducing the perception of pain. This is something that’s very important for people with severe burn injuries who have burned and lost 50% of their skin. It is excruciatingly painful to do the wound changes. They don’t have skin. It’s completely burned off. They’re finding that with the use of VR, they’re able to tolerate a lower level of opiate painkillers. They have less fear and anxiety built up about the wound dressing changes because they know that they’re going to be distracted. They’re not seeing what’s going on, and you’re not paying as much attention and they’re occupied mentally.
There’re also some other use cases for VR. They did a study with twelve paralyzed patients that they were able to show in VR, there’s this very interesting phenomenon where if you show the paralyzed limbs moving and the physical therapists move the limbs, you start to regenerate neural growth where they were able to regain motor function in parts of the body that were previously paralyzed. It’s a fascinating study if you google it.
It goes to show that the effect of VR has on the brain alone is very powerful because it’s so immersive that it can be nearly indistinguishable for the brain from a real experience. You see people on the edge of a cliff in VR and consciously, you’re safe, you’re in your house. There’s no hole in your floor. People, as soon as they approach that hole, they lose their balance and fall.
In the Oculus with the plank simulator, everyone should try it. It’s insane because you can have that exact feeling.
People fall. It’s hilarious.
They do. I put my dad in it. He would not step off the plank-like, “Nope. Not doing it.”
It preys on people’s fear of heights and be falling. It’s like your carpeted house is part of the brain that it does not accept.
The one that fascinates me the most, I don’t know anything about it, but I heard about a project where Navy SEALS or something, were using VR to treat PTSD. 100% of Navy SEALS have PTSD. It’s part of the job. I don’t know anything about this stuff. I’m making this part up, but in what I learned about trauma before, it seems to me that a lot of cases of PTSD where you get yanked out of a situation before your brain got to finish a story.
Your brain gets stuck in this cycle of trying to find an ending for the story that never got finished. You’re stuck in that spin cycle. With VR, what they’re doing is they’ll put you back on the battlefield where your buddy got shot or whatever. You’re there and you get a chance to finish the story. I’m making that part up. I honestly don’t know what they do. I made all that up but maybe it’s something like that.
From what I’ve seen, one of the issues with mass adoption and mass scaling of that is PTSD is personalized visually, which means some 3D designer has to rebuild like, “Was there an exact incident in Afghanistan where this is what happened?” The next person might have had a completely different experience. They have to rebuild. It makes it a little bit more expensive and harder but it seems to be effective because through this therapy, they can relive the situation, and they realize that they’re safe now and they’re not in the war zone.
With the right kind of therapist, they’re able to revisit these emotions. There seems to be a pretty good high rate of treatment for this and PTSD. The circuitry in the brain is rewiring to create hypervigilance, which is you’re in a state of constant anxiety, you’re sensitive to sounds, and sensitive emotional triggers. It’s sad because it’s such a massive issue in the United States, PTSD with veterans. They’re not doing a whole lot to treat them. It’s an area that they deserve to have a lot more options for therapy.
Fully understanding how mRNA works is the Holy Grail of curing people with congenital diseases by long-term altering their DNA.
TweetI have a friend who’s a pediatric doctor and he wants to use or has used, I don’t know what the status of it is, virtual reality and ketamine with kids who have a variety of different problems to help them adjust. It seems like a frontier.
I’m working with virtuality with ketamine. I would like to see data on the long-term safety of any type of psychedelic on a child. Some of the early research that I did when I was a teenager was on psychedelics on the developing brain. Your brain is still developing up until you’re about your early twenties. You’re not fully formed. The question is, “Are we causing any long-term damage to a developing brain by exposing them to psychoactive substances at a young age?”
Some of the data that I produced seems to suggest that there might be long-term effects. I focused on cognitive development in adolescent rats with a substance called the five immunity IPT, which is a tryptamine psychedelic drug. We did find some minor deficits in spatial navigation and flexibility in learning related to the serotonergic pathways in the brain that are associated with memory and flexibility learning and it wasn’t massively drastic.
These rats probably weren’t going to have a good time without MapQuest or GPS. Now there are some data coming out saying that teenagers that smoke marijuana may have some brain issues later in life from smoking early. I have mixed feelings on the whole idea of psychoactive for children. Although I’ve seen some interesting case studies that some of them were not published for fear of legal reasons. There were some children that were semi-autistic, born mute, and could not speak English.
There was a story that I had heard from somebody reputable where the family was associated with some major hippie touring bands of the 1960s and the child accidentally got a piece of candy that had lysergic acid diethylamide, LSD. The parents freaked out. They’re like, “We don’t want to go to jail.” Shortly after the incident, the child began to become verbal.
It’s interesting now because, in the past few years, the major breakthrough is we now have FMRI studies of brains on LSD. We’re seeing the hyper-connectivity between parts of the brain that were not connected. We’re seeing different parts of the default network that are cut off. It’s was a totally different operation of the brain. Now they’re even suggesting psychedelic psilocybin mushrooms for patients that are in a vegetative state. They think that because it does regenerate neural tissue, can we wake them up out of the vegetative state? That’s interesting.
Would it be amazing if we figured out that anyone can be brought out of a coma?
It’s possible with people with brain damage. We see with neuroplasticity that some people that have had a traumatic brain injury, even though that part of the brain has become as ischemic and died, they’re now seeing with DMT, LSD, psilocybin that they’re able to regrow new neural connections. The brain has fascinating neuroplasticity because it’s able to remap. Once you’ve lost some important part from brain damage, you can often remap to a different location. You get some interesting results.
It goes against the old school of all the neurons that you’re ever born with and they die over time because you drink alcohol and you do this and that. Now they’re starting to say that maybe that’s not true. It seems like we are still regenerating. There are stem cells in the brain. From what I read, alcohol is not particularly kind to your neuro stem cells that you do have present. Personally, alcohol is a toxin that should be moderated upon. It’s been around for millennia.
Its effects are at least well accepted. I don’t drink at all.
We’ve seen people live to 120 years old who drink a glass of whiskey a day.
I learned that in junior high. Alcohol kills brain cells. I figured I might as well keep as many as I can. I never started.
It’s an interesting social lubricant. You’ve seen it in Greek times and ancient times. It’s ubiquitous through all stages of human culture, some sort of fermented alcohol. It’s not a drug per se. It’s a toxin. You’re poisoning yourself. The effects that you’re feeling are the effects of being poisoned. It’s interesting to see how much of the brain is generative and neuroplastic.
Looping back to exosomes, now that we can get them through the blood-brain barrier, some of the damage is being caused by stroke or by exposure to chemicals or by various brain injuries or drug use. There’s a high probability that there might be between psychoactive substances like psilocybin mushrooms for example and between stuff like exosomes that are showing efficacy for treatment of post-stroke and all these other neurodegenerative conditions. There’s some possibility on the horizon of being able to repair some level of brain damage. Who knows? Maybe stave off dementia or have some treatment for dementia. I’m interested to see how far this goes.
What do you think the near-term priorities for exosome research should be?
There are many different areas.
Whatever it is, there can’t be enough.
It’s connecting back to what I was mentioning earlier with the big pharma companies that have their one-hit-wonder drug that does the one thing and they poured their billions of dollars of research. If they fail the clinical trial, it’s garbage unless they can repurpose that.
Can exosomes cure erectile dysfunction? They then could get all the funding they need.
There are people who claim that it does. I haven’t seen solid research on it. There are clinics advertising this. There’s this little gray market going on. The FDA, their stance on it is what they call selective enforcement where they’ve agreed to look the other way as long as the companies are not manufacturing it and marketing it explicitly for injection. That’s not legal. A drug is injected. They’re marketing it for topical use. The doctors legally have the right to use it off-label for whatever they would like.
Is there any topical use of exosomes that does anything?
With the cosmetic clinics, there are all these interesting Vampire Facial procedures, post-laser resurfacing microdermabrasion mixing it with PRP. They use it for hair-loss.
What’s PRP?
Platelet-rich plasma. You’re essentially extracting from your own blood and then it’s being returned to you. It’s being ultracentrifuged and returned to you and injected back into you. You’re back to the scenario of your old cells and you’re giving your old cells back to you. From what I understand, the PRP makes scaffolding.
In Korea, they already have a multibillion-dollar exosome company. Korea’s skincare industries are massive. Most women have plastic surgery at a young age. I was talking to some of my female Korean friends. It’s normal for your parents to pay for a nose job and eyelid surgery. You’re expected to have flawless skin. It’s a massive beauty industry there.
In the United States, we have a big regenerative anti-aging market where a lot of people would like to live forever, lifespan extensions. It’s getting into is it pseudoscience or not? If people have the money to play around with that kind of stuff, I don’t see the issue. It’s one of the only substances that I’ve seen working in pharmaceutics that does not seem to have a detrimental side effect that I’ve seen.
If you look at something like Tylenol, which has a massive amount of overdoses, a massive amount of liver damage, all kinds of side effects. You have something like the exosomes, there are not many reports with the exception of a few unscrupulous labs that are selling contaminated products out of the warehouse, basement, or whatever. That’s why the FDA does need to step in and regulate a little bit better because those are the people that mess it up for everybody.
Stem Cells: VR alone is reducing the perception of pain, which is useful for people with severe burning dreams.It’s relatively safe to try different things with this stuff, it sounds like.
We have not seen off-target or downstream effects thus far. I’m not saying that there isn’t.
People should be allowed to try it. We have enough extra humans anyway. Some of them can be devoted to exosome research of their own volition.
I was one of the first guinea pigs. I had myotonic synovitis and my wrist was 99% cured. For that, I had five CCs of an exosome and saline preparation that was injected into the carpal tunnel. I had severe inflammation of my tendon from repetitive stress injury from poor risk posture when typing for my entire life.
In the past 5, 7 years or so of grad school, it became excruciating. The nerve pain that was shooting up my elbow made it unbearable for me to use a cell phone, to type, or to use a computer mouse. I ended up having the product injected into my wrist and I started feeling improvement that was not placebo within a few days.
Eventually, it’s been several years now and the pain is 99.9% gone. It’s what converted me over like, “This is a real product.” It removed the inflammation. Hand surgeons were saying, “There’s nothing we can do about it. We can inject corticosteroids into it.” It’s not a long-term solution of steroids injected into anything, atrophy muscle and the atrophy tissue. It depresses the immune system. Steroids are not a good thing.
I was at my wit’s end because I had gone to multiple top hand surgeons in Miami and they’re all telling you, “It’s not carpal tunnel syndrome. There’s nothing we can do about it. We can’t do the carpal tunnel release surgery because you don’t have a carpal tunnel.” What do I do now? I’m learning how to type with my left hand. I’m flipping over my brain. Finally, I was like, “I’ll try it. Why not?” It was life-changing for me.
I haven’t had an IV yet. It’s something possibly on the horizon. If I do get COVID, I want to get an exosome treatment because we’re seeing now there’s some IND, Investigational New Drug Applications, with the FDA. We’re seeing a lot of the detrimental symptoms of COVID is not so much from the virus itself but it’s from the immune system going hyperdrive. Your body is starting to attack its tissues in response to the viral infection.
Oftentimes, the viral infection clears out but your organs are still being attacked and attacked. This cytokine storm of inflammatory molecules thinks that it’s being helpful by continuing to attack the tissue where the virus was initially. That’s where you end up with multi-organ system damage. We’re seeing brain inflammation where people are starting to see hallucinations. It’s almost schizophrenia. These are people with zero mental histories of anything. You’re seeing young people with kidney damage, lung damage, and repetitious pneumonia.
You’re thinking that it might be possible to inject somebody with exosomes who had COVID and it might reduce the possibility of this cytokine storm?
Yes. It seems like for the subset of people who are experiencing the cytokine storm, there are some case studies and there are a few hospitals that are already incorporating it. There are a few controlled trials that are underway. There are certainly some companies submitting INDs. Not necessarily exosomes but there are a few stem cell companies submitting that are already in early clinical trials. With a lot of the use cases for stem cells, it’s fair to say that stem cell exosomes are possibly efficacious for some of the same indications. With a safety profile and better ease of use, you can transport it much easier. You can throw it in the freezer. You don’t have to worry about frosting live cells. They’re not alive.
I’m excited about what I learned about all this from you. That’s cool. I learned a lot.
There’s so much more. This goes on and on. It’s fascinating because it’s one of the only biopharmaceutical drugs that almost has an infinite possibility of indication and formats. You can have nasal sprays. You can have injections. You can have a transdermal patch that contains a skin permeability compound like DSMO that allows it to be absorbed through the skin into a joint without having to have needles. There are many interesting applications.
I can’t wait to have a problem so I can get some.
You can hop into one of those life expansion clinics on the West Coast.
Get some exosomes.
That’s the hot tricky thing right now for some of the people that are into lifespan extension and biohacking. There’s doesn’t seem to be a negative side effect profile thus far that we know of. There’s a small chance that if you have some hidden cancer tumor that you’re unaware of, it’s possible it could increase the growth in some manner through additional angiogenesis. Also, additional acceleration of biomass, it’s something that we don’t know for sure. There are people that are on the opposite side of it. They say, “No. It’s efficacious against tumors.” We need to see more data on that.
It’s a frontier. Do you have any questions for me?
Probably a lot.
I’ve been picking your brain.
There’s a lot in your brain to pick.
Now is the chance. You can ask the most incriminating questions you can think of.
Sometimes, you have to go beyond your boundaries to make actual progress.
TweetDon’t challenge me to that. Is that within the topic of healthcare?
Anything. I don’t care. It doesn’t matter.
Are you becoming more involved in the healthcare space?
No.
You’re mostly in the application of technology to solving more global problems.
Exactly. I want to try to close that gap. What it comes down to is you have to understand the problems. A lot of times, the people who understand the problems are so deep in it that they don’t also have the capacity to learn about the whole world of possible technologies that could affect the problem. It’s almost always true. On the other side, you have people who know a lot about technology. They’re specialists in something, but they don’t understand the problems that they might be able to affect. They’re often far removed.
As an inventor, I was always trying to escalate my knowledge on both sides, know more about what technologies exist and are coming, and know more about what problems exist in the world. Even if I can’t become an expert in them, I want to know the people who are. That way, sometimes you can match them up. All the time now, I’m trying to fill my head with what problems can I learn about and different industries, regions, people, and get a sense of them. Even if I can’t fully understand them, I can learn more about them.
On the other side, for me, it was computers. I wanted to learn everything I could about what’s not just everything about computers but what’s possible with them and try to understand where they could go and try to take them to new places. I’ve been making that my whole career. In some sense, we’re still at the beginning.
Computers have been super powerful. Outside of computers, where I know a lot less. There are also these amazing frontiers like gene editing, exosomes that I have no idea about, and material science. There are all different areas where you get this progression from scientific discovery. It gives you a sense of how things work.
From there, you can advance on, “What’s technically possible?” That’s where you’re taking the output of scientific discovery and trying to figure it out. It’s almost independent of whether it’s a good idea or not. What’s technically possible? I like to be in that space. What could we do with the knowledge we’ve attained? Every day, you get new scientific discoveries. There’s a new sensor, a new algorithm, a new paper on how something works.
To me, that’s input and I want to know so that I can match them up. There’s probably a real sharp limit on how many things I’m going to affect but that’s part of why I like sharing these conversations on the podcasts because then other people can learn those things, too. I’m learning them but maybe somebody who’s going to be useful at advancing exosomes will listen to this and get excited about it. Probably, I won’t be that one but somebody else could be. A lot of people don’t get the chance to come and hang out with you and pick your brain.
For me, what’s exciting is it’s a much longer path than a traditional path of being a specialist in one field. I like trying to learn a lot in disparate industries and fields and trying to see what the crossover is between these disparate industries. You have science and technology. You have something like art or architecture. How can you combine these different areas? You have AI and then you have molecular drug design. You have something else. I like seeing the crossover of it. It’s things that if you don’t have a background in multiple fields, you’re never going to come up with these ideas of cross-pollination.
There’s a real value in having depth in something. I meet a lot of generalists who haven’t done that. That erodes their ability to create a sense of perspective with all the new things. If you explore different areas and you’re trying to learn about different things, you need to be able to connect it to something. If the thing you’re connecting it to is deep, then you could have an effect. When you look at the invention work that I was involved in, all of our inventions are at the borders of different areas in science and technology. Have you read Consilience, E.O. Wilson’s book on this?
No.
You probably heard E.O. Wilson. He was a badass in science. He wrote this amazing book. I don’t know if he’s still alive. He was pretty old at the time. The book was trying to show scientists that these artificial constructs of chemistry, biology, physics and mathematics. It’s all science.
They all interconnect.
Those silos are keeping us from advancing. Nobody’s contributed more science than E.O. Wilson, so no one can argue with him. It’s pretty amazing. That’s a good one.
For me, my hope for the future is I want to learn quite a bit in one field and then move to the next field and move to the next field.
Life extension is going to become necessary for you.
I see that there are connections that people are missing. You need specialists. You must have expert specialists. You also must have people that are more generalist because they can see where all the different areas connect. You have your specialists who have the expertise in those fields. If you can see the bigger picture, you can see connections that other people can’t make. That’s where the new innovations are going to be coming from. It’s this cross-pollination of all of these. These fields are advancing fast right now. It’s exponential. Compared to when I started my Doctorate versus what I see now, I can’t even keep up.
No one can.
I’m trying to keep up with multiple fields of science. The papers that come out every day are mind-blowing. Some of this stuff is amazing.
It’s exciting.
I love it.
The tools are better than ever.
The tech is getting amazing. Even in biotech, we’re getting further and further down into nanoparticles, nanoparticle medicines. Regenerative medicines are getting more and more of synthetic biology and gene editing. It’s going in all these directions that when I started this journey as a child. It’s sci-fi coming real.
It’s amazing. My entire life has been characterized by the fact that I got a computer early on at a young age, and I stayed ahead of people because I stuck with it. You got into the next frontier, which is all that’s possible with genetics and with the future of biology. Now, we’re advancing that because we have computers, essentially. It’s too late for me to get into that. You got in on the beginning of it.
I don’t think you’re too late, though.
The world doesn’t need me for that.
Even with me in the beginning, I still feel like I need to catch up with people. My little insecurity being a generalist is I know I’m never going to have the depth that a specialist has, and I’m happy with that. I want to have generalists. I go as deep as I can. I don’t go to shallow level. It means that for someone that finishes their PhD and their one specialty, whereas I already finished my Doctorate and I’m still going deep on my own personal time.
The next thing is like, “No. It’s going to take me an extra 10 or 20 years to reach the level where I can start to see how are all these different things going to connect and how I can innovate and create something that all the specialists we’re not going to be able to meet?” It’s a little frustrating. This is a longer-term timeframe.
Some people have to be looking out of the box bigger. I’m not necessarily saying that I will innovate or create something, but it’s a possibility if they continue. A lot of people should try to learn multiple areas if they’re able to and motivated. That’s where the best innovations are going to come from, especially now that we can apply all this new technology to other healthcare principles to biotech principles. It’s such an exciting time. The equipment that is coming out is so advanced, and it’s fascinating.
Stem Cells: Oftentimes, the viral infection clears out, but your organs are still just being attacked and damaged.If I have a stem cell in a microscope and I put it next to an eyeball cell or some other cell, can I watch it transform into that on time-lapse? Is that something that someone can observe?
I suppose you could set up a time-lapse camera and see it.
How long does it take for a stem cell to turn into a skin cell or some other kind of program?
Something that’s often done with most stem cells is they’ll do a differentiation test where they will add a certain compound to ensure that it will turn into chondrocytes or adipocytes, which is the bone, the cartilage, and the fat. Osteoblasts chondrocytes, that’s a characterization confirmation to see if it indeed is undifferentiated.
Also, take one and test it to make sure it’s good.
Yes. In theory, you could set up a time-lapse camera and watch it. I’ve never tried it.
I’m going to look on YouTube. There’s got to be one.
I’ve played with microscopy of stem cells. They’re fun to look at. When you have a beautiful cell culture, they grow in a swirl form. It almost looks like art. If you print it and put it on your wall, they look so beautiful.
That should be your art project. Thanks for doing this.
Thanks for having me. It’s an honor.
People are going to love it.
I hope so.
This is an amazing conversation to share. The best ones are when you do more of the talking than me. We got a lot out of you. Thanks.
Thank you.
Important Links:Dr. Melissa C. Selinger, Pharm.D
Scientist, #MeToo survivor, former biotech exec/founding team, tech artist
ssd.jpl.nasa.gov/sbdb.cgi?sstr=21744+Meliselinger
NASA minor planet 21744 Meliselinger (1999 RF168)
Published neuropsychopharmacology research
https://www.researchgate.net/scientific-contributions/Melissa-C-Selinger-31520206
Upcoming researchKVR
Idea conception for and first author for KVR: A novel pilot virtual reality adjunct therapy for intravenous ketamine infusion for pain and depression in 18 patients, collab with Hamilton Morris
Journal publication TBA
Early KVR media coveragehttps://www.practicalpainmanagement.com/patient/virtual-reality-for-pain-depression
https://www.freethink.com/articles/virtual-reality-ketamine-therapy
Recorded on March 7, 2021The post Exosomes, Stem Cells, Ketamine & VR — Dr. Melissa Selinger appeared first on .
1,279 Listeners
8,555 Listeners
26,281 Listeners
1,003 Listeners
8,633 Listeners