Mental Health Geneticist, Herbert Lachman, M.D.

0:00 Hi, it's Doctor Robert Siker. Welcome to a new episode of Doctor Podcast. Today I'm pleased to have an excellent guest, Doctor Herb Lackman. Dr. Lackman is a professor of medicine and psychiatry at the Albert Einstein College of Medicine here in New York City, and you can see his information here behind us. Doctor Lackman is also an Associate professor of neuroscience and Genetics, also at the Albert Einstein College of Medicine. Today we're going to discuss some exciting topics about genetics and psychiatric and mental disorders with Doctor Lackman.

0:41 Herb. Thanks for coming today, really appreciate it. Yeah, it's a horrible rainstorm out there. I got drenched, my suit is soaking wet. So thanks. I came early so that I would avoid came really early. I'm one of those types who comes to airports really early. Well, that's good. Hopefully the the rain clears up now. Herb, you have a a fascinating background in that you trained in internal medicine and then did a fellowship in genetics, I'm sorry fellowship in hematology and oncology. But somewhere along your career you've switched to neuroscience and psychiatry and genetics.

1:20 Can you tell us why? I made a bad mistake in my life. So I was I was a cancer researcher early on and I was studying two cancer genes, CMIC at NYC and P53, and it was very exciting, a great time to be a cancer biologist because all these oncogenes were being discovered. Then I realized that I was kind of a small fry. I'm just starting out. They were really great investigators, Nobel Prize winners in this field. And I began to get a little antsy that maybe I would make. I would not make a major contribution.

1:54 And around the same time, a couple of papers came out in Nature and Science pointing to regions on chromosomes 511 and X as having genes involved in schizophrenia and bipolar disorder. Those are false positive findings. It turned out well. It was. It was enough to get me really excited about thinking about about these genes that can cause these incredible changes in a person's behavior. So that sort of got me started to think about about about bipolar especially. I became a little bit obsessed with it and they just tried to play around with models that might result in these drastic mood changes.

2:34 And eventually I was able to convince the the chair of psychiatry at the time that Doctor Herman von Prague. That's it, Albert Einstein. Yeah, a a really great early biological psychiatrist to start a a psychiatric, A genetics unit. And he pointed me his head along with former classmate Dimitri Pablos. And that's how it got started. And at the same time, Dimitri was involved in this disease called VCFS, VLO Cardio Facial Syndrome. It's got five different names. It was discovered at at Montefiore and it causes a whole slew of general anomalies and and cardiac defects.

3:12 And about 1/3 of those patients have psychiatric disorder, schizophrenia or bipolar, and it's due to the loss of 50 or 60 genes on on chromosome 22. And one of those genes is a gene called Com T, which I began to study and I created a kind of a cottage industry of comt related disorders that still persists. So you've discovered genes associated with bipolar disorder. What about schizophrenia and autism? I know you're interested in that as. Well, so, yeah, so we, I mean the COMT gene ends up being a variant.

3:54 I discovered a common variant in that gene that causes a major change in activity, and people began to look at that in schizophrenia, bipolar, Parkinson's disease, everything. Psychopathy, pain, sensing pain. And it turned out that it only has a few effects on people. And one of the problems is that is that in order to prove that a genetic variant is causing a problem, you need to have very large sample slices. And we didn't really appreciate that until five or six years later anyway. I end up not end up doing work on disease modeling with these things called induced stem cells.

4:41 That's what I've been doing for the last. Years or so right? Stem cells are a hot. Topic. That's right. Yeah. Back in the old days, from what I recall in my training, most psychiatric illnesses were thought to be sometimes familial but more environmentally induced. Is there increasing evidence that there's a genetic basis for them and certain environments trigger the clinical disorder? I tell psych students, medical students who want to go to Psych if they thought they would escape genetics, they were wrong.

5:16 It turns out that autism, schizophrenia and bipolar have a very, very strongly genetic maybe 80% of the variance is due to genetics. It's genes really are the main, the main cause of those illnesses. They also may be environmental factors that have an impact. But it's primarily genetic. And now we know. Now we have identified, my colleagues have identified hundreds of genes that cause each of those. It's a very, very complex trait. So it's not just one gene, it's a combination of various genetic defects that in combination cause the clinical disorder.

5:53 Right. So in any one person you might have two or three genetic variants that are doing it. And then someone else, they might have genes AB and C and someone else might have genes CD and F And so it's not everybody has doesn't have these hundreds of mutations that they have only a small handful. A few of them, yeah. There are some eye diseases as well similar to that. I'm an ophthalmologist. Does you know where, for example, retinitis pigmentosa has a variety of different genes that can trigger it?

6:25 Are there tests available for these genes? Can someone have a genetics test to see if they have the schizophrenia or autism or bipolar? Gene well in autism. The standard care is to do a genetic analysis, typically for Fragile X, which is the most common cause of autism. Maybe 5% of all autistic cases. That's a gene defect. Yeah, Fragile. X. And so people, kids, are tested for that and then they are analyzed using these things called array CGH arrays, which look for copy variants, which are these large chromosomal changes.

7:08 And then after that they can get the DNA sequencing, exome sequencing, which is DNA analysis looking for specific mutations in the coding regions of genes. That's standard care. And it's not that we can do anything about it now, except we can tell the families they're relieved. They want to know what's going on. They can use that information in some cases for family planning, but it hasn't trickled down as much in the adult psychiatry community. They still they don't. So people are not really getting analyzed that much.

7:40 Some are. It's changing. But I think it's very useful to get these studies done because families now know it wasn't a drink that I had when I was pregnant. It wasn't this infection. I have this gene or in some cases it's a Nova mutation, meaning that it happened in Germline and now we know so they can form groups, Facebook groups and start nonprofits and it's very, very important to have that information. Speaking of groups and nonprofits, you do a lot of research on these illnesses and people can contact you right with this information in the background so they can.

8:20 E-mail me and I'll be happy to. Right. So if anyone in the audience watching this has any family members who has any of these psychiatric illnesses and is interested in more information, or possibly anyone who's interested in providing funds for additional research that Doctor Lackman is doing, please feel free to contact them with the information. In the back you mentioned autism and and genetics. I've asked a few guests already about autism and relation to vaccination. They all told me that there's no connection to vaccines.

8:59 Do you agree with? That oh totally. I mean the the the the Wakefield study that started this whole thing was an unbelievable it was a mistake. I I don't know how it got past the review is how it got past the editors. It was a horrible paper and scientific fraud was committed, ethical violations occurred. It was really an amazingly poor study and it was retracted by by Lancet and no and then in many studies since then, showing that there's no connection at all. The problem is everybody gets vaccinated as a kid and a lot of kids.

9:35 Autism is very common now. One in 40 or so, and every now and then the kid will have a regression and it's temporarily related to them getting vaccine. It's like us, you know, when you have elderly parents, you always dream about your parent dying. Every now and then, person in the world is going to have a parent die on that same day and you'll think, Oh my God, I dreamt that my but no, it's just it's totally coincidental. So it's a coincidence? Yeah. There's no cause and effect. Not. Only that these vaccines actually improve the brains of kids.

10:09 So back in the day before the MMR vaccine was was was used, That's mumps, measles, mumps and rubella. There are 3,000,000 cases of measles every year and one out of 1002 out of 1000 died or developed brain inflammation called encephalitis and that leads to a brain disorder, autism and other cognitive abnormalities. And also back in the day we had the rubella, German measles, which is a fairly benign disease, but if a woman gets it in the first trimester of pregnancy, they, the child would have congenital rubella syndrome, which also causes brain damage.

10:50 And I just estimated that, you know, since MRMRMRMR vaccines that came into use maybe 40 or 50 years ago, I think that maybe a half a million people in the United States alive today have normal brains because their parents and they were vaccinated. Well, that's good to know because unfortunately there's still bad information out there in the media about the MMR vaccines. I have an anecdote, if you don't mind, about this. Sure. So I was dealing with a family with a bipolar disorder and doing a genetic analysis and the the the son of one of the individuals came to, was it at the house?

11:29 I was drawing blood DNA and he didn't have bipolar, but he was diagnosed with Asperger's. It's now part of the autism spectrum and he was a very nice young man, but I kind of suspected something was up. So I did a chromosome analysis on him and he had a duplication of a region on chromosome 8 involving some 200 genes. Very well. Rare, but well known to cause a some developmental issues and Asperger's and he was having trouble with math and who's getting tutors and the parents were really frustrated that he couldn't get past a certain level.

12:08 So I called the parents and said, look, it's good that you're getting this tutoring, but there's a window here because your son has this chromosomal abnormality that's well known to actually cause math problems. And over the phone one of the parents said to me that I was wrong. The reason why he had this problem was that he was vaccinated as a kid. So even when you're given the the genetic information, right. So strong is this belief about the vaccines that it just makes you delusional about it.

12:39 So the. Media has tremendous influence on what people think and what they know or what they think they're known. They have these narratives. These narratives are powerful, right? And the more powerful than stats. Right. More powerful than than science. Another thing I I want to discuss with you is you mentioned stem cells earlier. I had a guest a few weeks ago, Doctor James Griffo, who's the head of the fertility center at NYU Langone Medical Center here in New York. He mentioned that he is creating five day old embryos, which are stem cells and then implanting them in the uterus of women who can't get pregnant naturally.

13:20 So you're doing stem cell research. You mentioned there induced pluripotent stem cells, which I'll just call IP stem cells for short. These are similar but not the same as embryos. Can you explain why you're doing that and what the issue was with using stem cells from embryos? So the structure that's implanted in women who need to conceive in vitro fertilization is a blastocyst which is about 200 cells, A5 day, six day old embryo and those contain ES cells, embryonic stem cells. Those stem cells have this incredible capacity to differentiate or turn into any cell type of body.

14:08 So ES cells become heart, muscle and and brain and neurons and and and bone and so on. So they have this intrinsic capacity and of course they grow. You grow into a human being from that. And in 1981, researchers were able to isolate the embryonic stem cells from mice, and those were used to create these mouse models of disease, now thousands of them. That led to a Nobel Prize in 2007. To the researchers in 1995 or so researchers at the University of Wisconsin, Madison, this isolated human embryonic stem cells, and these were touted as being useful tools to replace dead or damaged tissue or cells in people.

14:57 So if you have a spinal cord injury, or if you have ALS or Parkinson's disease, these cells can turn into the appropriate cell types that can, theoretically at least, replace the damaged. Tissue. So you could make nerve cells. You could make kidney cells, heart cells, any cell. Whatever any cell you want. And the problem is that when you do that you are. These embryos by the way are are obtained by with informed consent by parents who don't use them anymore. They they they get the one or two implanted then the rest are not used.

15:30 So they're frozen in these facilities and they donated these these samples. But the in among the ultra right religious community, these embryos, these 5 balls of cells are human embryos and if you destroy them what you need to do to make human embryonic stem cells, you're killing a person. So that has created this, this climate in the in the US making it very hard to do that kind of research. You can still do it but there were times when you there were federal bans on on on new making new stem cells.

16:07 Some states have bans now. So if you're doing work in this area of research, you don't want that undermined by politics, right. So we needed to come up the field needed to come up with a new technique to produce cells that mimic ES cells. But we're not not involve the use of an embryo. And that's where the these IP stem cells came in were discovered. And they were discovered by Shinya Yamanaka, a Japanese researcher who provided the technique for making them from skin cells. You can take skin fibroblasts and turn them into stem cells that resemble embryonic stem cells, and those are the cells that are now used primarily to

16:59 being investigated to use for replacement therapy. So there's no controversy cuz there's no embryos. Involved and they're better in some way. Well, in many ways they're better because they're derived from the person, right? And if you use embryonic stem cells, you might have, and you create, let's say, dopamine neurons for Parkinson's disease, you would need to treat that person with immunosuppressants. And if you're using your own cells, then that's. Right. The body doesn't reject your own cells, even if you grow them in a test tube or an incubator.

17:32 Of something, but it's really expensive to do that. It's. Very expensive. Yeah, and. Right now in a few. Years. I mean, you have to grow these cells. It takes many, many months. If you're growing them from patients, it costs hundreds of thousands of dollars. And for disease like Parkinson's, which is a public health disease, and you know a million people have it right, you know, 1,000,000 * 1,000,000, it's a lot of money. So it's not really feasible in the long run. But only the billionaires can afford it right now.

18:01 The way it is now, yes, right. I see. How do you direct AIP stem cell, not an embryonic stem cell, to become a certain organ or tissue? How do you? Is it a chemical? Is it some sort of other magic potion that you use to tell that stem cell to become skin or bone? There's a little magic to it. A little magic, yeah. But so the people who do this, and I'm I'm, I'm basically following other people's recipes. So I don't do this this work. Now you make neuronals. Right. Which is a brain, a type of a brain cell from a stem cell.

18:37 That's right. So basically what you what what is done is you try and mimic what's happening during embryogenesis and you add growth factors to induce differentiation. You add certain inhibitors of of pathways that keep the cells as a stem cell and you play around with the with the with the recipe until you come up with one that produces a very nice yield of the cells of the cells that you want. I see. So you try various chemicals and see what they do and and how that cell is directed and then you keep on improving.

19:12 On that, Well, the people who hey, those first discoveries did that. I just followed the recipe. I see it works. So my job is not to do what they did. My job is just to copy the recipe and then do my research from. That so you don't reinvent the wheel you know how to. Bite it. I wouldn't mind doing that, but I don't have a lab big enough of funding to play around to tinker. With well, after this program, when people contact you with this information and want to donate millions of dollars to your labs, that would be nice, right?

19:44 Perhaps you can move along. So is it possible, Let's say you had enough money or let's say 5 or 10 years from now you could just grow brain cells? Or if somebody needs a kidney, could you actually grow that in the lab and then replace that as an organ? So the work that we do is we we study these neurons that we make from from IP stem cells from patients we're growing grow patient specific neurons. Where do you get those cells from? What part of the? Patient I get them from blood. From blood. Yeah.

20:21 So we take white blood cells or skin sometimes and we turn them into stem cells using the Yamanaka formula or current formulas. And we grow these cells and then we can differentiate them into neurons and other cell types. And we study. So we're not growing these cells to replace anything other researchers are doing that. We are just creating models of disease. So we're studying what is the effect of the schizophrenia and also some genes on the cell, on the neuron, how is it affecting other proteins and other genes, how is it affecting the electrophysiological properties of these cells.

21:06 And the point there is to find these pathways that you can then

21:12 after which you can find drugs that might block or or reverse the abnormal pathway. So you could take some skin cells for example from somebody who has schizophrenia and A and a genetic defect that you've identified. You can then grow those cells, identify where possibly the error is, and maybe that will help come up with ways to treat that in the future. Right. That is what we do. That is what many labs do and they're actually are some phase one clinical trials being carried out now to test different drugs that were found in various diseases.

21:51 So it allows you to target treatment very specifically for individuals as opposed to now where people are just given medications at hopefully work for them that are not specific. Right. So this is precision medicine. Yeah. And this is, and in these disorders, we have hundreds of genes. It's very hard to find one treatment that'll fit everybody. So that kind of medicine, that kind of treatment, dealing with the person's specific genetic abnormality is going to be really critical. How long do you think it'll take?

22:31 Next 5-10 years? We'll we'll see very targeted treatments for specific disorders. It's I'll tell you I'm really bad at at making those I've been bad I've been off so much. I'm predicting things like that that I I try to stay away, but now that we. How are you in the stock market? My wife handles that. All right. So I, I, I mean the technology is so amazing now, right, that I think that within a few years we'll have some, some therapies. The problem is dealing with a disease that occurred during brain development and you know how much of that is cemented into the into the into the brain's anatomy, how much, how much can you can you reverse, right.

23:15 And this is the big, the big unknown. But we know from from, from work done by bond, medical people, people who treat kids with autism and other developmental problems. Yet the one-on-one occupational therapy and speech therapy and this and that. Those workers have done something incredible. They've turned these kids. They've maximized what they can do. They've turned kids who would end up being institutionalized into kids who can be live on their own in some cases and and and work. I mean Down syndrome.

23:51 There's lots of kids with Down syndrome who are highly functional and that's only because of these of these non medical people and that means that the brain is plastic enough so that a person like me and my colleagues can find a drug that might mimic or enhance what these one-on-one therapists that do. So I have I'm optimistic that we can do something. We're not going to turn them into Albert Einstein necessarily. But let me tell you something. If you can get somebody with Down syndrome to travel independently and to live with a roommate, this is this is gigantic, right?

24:26 Gigantic. So that's the goal. Right. I just read a few days ago that some researchers actually got human kidney to grow inside of a pig by modifying the the genes. And the hope is that in the future we'll be able to grow a full-fledged kidneys or other organs in pigs which have a similar anatomy to humans, and then take that organ from the pig and then put it into the human. Well, another possibility is to create pure human kidneys in the test tube. So there are kidney organoids that are being made.

25:10 They're very small, like they can't do what a kidney does, but they are they. They do resemble kidneys. They have functioning, partially functioning nephrons, and at some point maybe growing those cells on some kind of scaffold might produce a functional kidney that can then be planted and again using the patient's cells. So you wouldn't get rejection. That I think is not. So that's not science fiction anymore. That's doable. Yeah, at NYUI, think they transplanted A modified pig kidney into a human.

25:48 Yeah, they humanized the pig, pig kidney. That's one approach, right? Still have a rejection situation, but I mean, anything you can do that will give you organ transplant, There's a shortage of donors. Right, so if you can use the patient cells, grow the organ that you need and transplanted, you avoid the entire rejection problem. You avoid all the toxic anti rejection. Right. No, it's it's it's it's something, it's something that I think will be done. It's I, I all the all the stuff. It's like it's like the the discovery of the the invention of the airplane.

26:25 I mean you have the right, the Wright, the Wright brothers, you know biplane. Now we have these jets Took a century, right? We're now at the Wright Brothers stage of of development in many of these treatments. That's a great analogy, but things are moving faster. Faster. Much faster. Right, so it could what took 100 years may take 5. Yeah, no predictions for me. But yeah, it's it's it's coming. Which leads me to the next discussion of gene editing using CRISPR technology, which is in the media almost every day.

26:55 Right, right. I read about it. Can you tell us about CRISPR technology, what that does and what the future of that is and how you're using it? Yeah. So CRISPR is fundamentally a gene editing tool and basically using CRISPR you can create, you can knock out a gene or introduce a patient mutation in that gene or correct a patient mutation to the normal variant. And this is all due to the ability of of of CRISPR to target very specific regions of the of the genome. And it's the reason why it took off is that the other techniques used to modify the genome in the in the same manner were really, really complicated really.

27:43 I mean it took months to to create the to do that. CRISPR is done really easily. It's a one. So really it's a one step process and it was discovered by by many investigators, but Jennifer Doudner and Emmanuel Sharpentier were the main discoveries. They won the 2020 Nobel Prize in Chemistry for that. And the technique is so elegant and so simple. And the thing that's amazing about CRISPR is that it is derived from microbes. It's it's a it's a bacterial immune system. And maybe 1/3 to 1/2 of all bacteria have evolved a Crispus system.

28:21 So we've taken this this system is meant to kill incoming viruses. Even bacteria are are infected by viruses and we've taken this, this primitive immune. Well, not so primitive. It's a pretty advanced immune system. We've taken this system in in in bacteria, big bacteria, and now we're editing genes and curing sickle cell disease with CRISPR. This has been done in a couple of patients. So this is really inventive. Use evolution of a basic science discovery into clinical application. This is the power of great science.

29:00 So basically you're able to take out pieces of DNA from a gene or put in? New pieces. Yeah, right. Exactly. Or put them wherever you want in, in combination. So once we figure out the entire genome, which I think has pretty much been figured out, you can, once you identify what every piece of DNA does, you could possibly edit it, change it. So if somebody has a disease, because they have 20 abnormal DNA segments in the gene, you could potentially take those out and put in the correct gene. Right.

29:38 So yeah, it's being done. It's being done. Now it's like Microsoft words. It is for genes. You delete, insert, yeah, it's the same idea, copy and paste. So those are so gene therapy is done on somatic cells. Those are cells in the body, right. They don't get into the germ. They don't get into sperm or egg. So we can take stem cells, like stem cells from the blood and we can correct the sickle cell mutation, give it back to the patient and they don't have sickle cell disease anymore. And you can do that now for many, many disorders of the many blood cell disorders.

30:16 It's much harder to do in other cell types. But even then it's being it's being done with these viruses that are engineered to target specific organs and cell types like the liver or even the brain. But it's it's it's very easy to do it on stem cells. You just isolate them from the person, do the CRISPR correction literally in the test tube and then inject it back into the person. You can't do that for a for a liver disease or brain disease. You have to have another delivery system that's being done.

30:49 What if you took an embryo at, let's say the three or five days stage and you knew there was a genetic defect there? Could you potentially take one of the embryonic cells, modify the DNA, get rid of that? Defect. Well, you can't do it in theory, but in practice it's not done because it's a ban on doing germ line intervention. And why is that? Well, one reason is that the CRISPR has problems. One of them is so-called off target effects. So you can direct the CRISPR complex to a specific site of the genome, but it also is so powerful it can knock out other genes.

31:32 So that's one problem that has to be resolved. So we don't know all the gene to gene interactions. In other words, if you change gene A, what effect might that have on gene B&C? Yeah, right. So that's that. And there's also a reluctance to manipulate the human germline. That's the main obstacle right now, right? Cuz then people wanna have 7 foot tall kids who play for the NBA, right? Right. We can do that to the Knicks. That would be. Actually, I'd be in favor of that happening well now. Or maybe getting a big lineman for an offensive lineman for the Giants that we can engineer a few of those that would.

32:07 Be very so if you want a 7 foot child who plays for the WNBA or NBA, contact Doctor Rackman and. He'll, yeah. So there's a reluctance right now to to do that. And there has been a case where that was done in China, right a few years ago where this investigator made a manipulated fertilized egg in twins and locked out a gene called CCR 5. CCR 5 codes for protein, that is, that's the receptor for HIV, the. Virus. HIV. So HIV gets into the cells by are binding to CCR 5 and we know from genetic studies that there is a variant found primarily in Europeans where CCR 5 doesn't work and doesn't form and HIV does not get into the cells.

33:05 You have two copies of that that's found in about 1% of Europeans. You are resistant to HIV. So those people are immune to getting HIV? They. Can get it, but it doesn't really grow and there are HIV strains that use another receptors. We want to target those. So there's a very good evidence that can be done. The problem is that it is medically unnecessary because the father was HIV positive and there are techniques to reduce the risk of infection. If fathers aren't uninfected, there's actually no reason to do that.

33:43 I see he was put in jail for he. Was jail for you, right? Fined. And no, it wasn't the first person in the history whose hubris got in the way of common sense. And it lead to really nasty consequences, right? So that's the right now we're not doing germline manipulation. Right, good idea. I've read some controversial information that maybe CRISPR was used to modify or create the COVID virus. Possibly. Is that? No, that's no, no, no, definitely not. Definitely not, no no. The COVID virus solves COVID 2 is too clever to be engineered by humans.

34:23 Really. Yeah, we have never we we can make, we can actually create a whole Organism in scratch, right. We can do that and a whole microbe criteria, but you can't create a new one. No one knows how to do that. Nobody and soloscopy 2 has features that nobody could have invented. So soloscopy 2 is a natural virus. There's a mutation that occurred, yeah. It's like all of the mutations that they occur in nature and they mutate quite rapidly and every now and then you get a mutation that likes human cells, and that's what happened here.

35:03 Now there may be other issues with source code B2 that we don't need to get into, but it was not engineered. I can guarantee that. All right. You heard it from Doctor Lackman, right? Another topic that I wanted to discuss that I know you're doing research in is basically psychiatric illness that occurs secondary to a strep infection, like a strep throat. Now, strep throat is one of the most common infections that kids get and that pediatrician see, and typically it's treated and it goes away. Rarely it can cause heart or kidney problems if it's not treated promptly.

35:45 But now in the last few years, there's a new condition that's been discovered. Tell us. About that. So the acronym is PANS Pediatric Acute Neuropsychiatric Syndrome and the strep variety is called PANDAS. That's what was the first entity that that was discovered maybe 20 years ago. And it was found that the kids were developing acute onset OCD, excessive compulsive disorder following strep infections and they responded to antibiotics. How soon after the infection did they get? Quite. Quickly. Quickly, it's it's it's sometimes overnight.

36:18 Usually it's in a few days. Wow. And sometimes the parents describe a light switch going on. And after a few years, it was realized that strep was not the only microbe that was inducing these acute syndromes. And the Pan's diagnosis was used to as an umbrella term. Strep induced OCD and other infectious disease induced psychiatric symptoms. And it's very controversial because a lot of doctors don't believe in it. There are no inflammatory markers. If you do a scan of the brain, an MRI scan of the brain, you don't see inflammation.

37:02 It's supposed to be a neuro inflammatory disease. But it turns out that that MRI scans are very often negative, even with neuro inflammation. And it's there's a lot of pan skepticism and it's not easy to distinguish between OCD occurring after infection with OCD occurring in kids as part of a psychiatric illness. But it turns out the pens is not just OCD. It's a combination of OCD, restricted eating, anxiety, rage, autonomic nervous system problems, 1/3 have joint inflammation. That's a whole slew of of of of of of neurological and psychiatric problems.

37:47 Very. Different from What's the evidence that it's related to a strep infection is, is there blood tests or serology that shows? That well, the ones that are strep induced, they usually have a rising title of strep antibodies. So if you do a blood test, you can see. It's not, you know, it's but kids have strep, right? It's not that easy. It's really not that easy. That's one of the reasons why it's controversial. I see. And do you? Believe it's a true entity. There's no question about it. I mean, we actually found some genes that yeah.

38:17 So no, I'm heavily involved in this condition now. So my group and my my Co investigators and many other groups are now doing gene sequencing to look for underlying mutations and we published a paper a year ago where we found 11 genes that with very, very rare rare mutations that increase that cause pans in 21 individuals. Are you saying that certain individuals with a certain type of gene are just susceptible to this effect from a strep infection? If they have the right kind of gene, get the right kind of strep, they get this.

38:55 Right. And it's not just Strep, it's many other, yeah, viral infections, Mycoplasma infections, yeah. So you have some of the genes are regulators of the immune system. So the idea here is that you have an infection that's triggering an overactive immune response. Some of the genes code for proteins that are seen in autism and it's triggering inflammation. We think through another another mechanism and it turns out that a lot of kids with autism have superimposed PANS. And you can treat the PANS aspect.

39:31 You won't treat the the autism, but you can treat the the the acute onset problems with other antibiotics or steroids or intravenous immunoglobulin really, but the responses. And antibiotics and steroids. Yeah. But not everybody responds to that, right, with this genetically very heterogeneous right, going back to the precision medicine idea. Right. And there are people in the audience who have family members with Pans. Can they? Contact me. They should contact me. Go to person for. Yeah, for that.

40:06 And yeah, so. Can you then take skin cells from them, stem cells and then investigate them and and see what genetic defects are present? Well, we're doing that now for one of the variants. So we've actually made stem cells and we are growing microglia to the brain's immune cells, which you think is cell type that's involved in, in this, in in transmitting the infection and the immune response in the periphery to a neuro inflammatory process. So we're doing studies on that and I'm trying to get funding now from the NIH to look at another gene that.

40:43 So we're trying to. It's very tedious work. It's very complicated, right? Tell us a little about the funding process. How easy is it to get money from NIH and other government sources as opposed to private sources of funding? You know, people have a misconception about what scientists do. They look at people like me and maybe lab codes that we're pouring 1 contents of one into another. And we have spoke all over the place, right? People who run labs like me, most of us don't do research. We have post docs and technicians and grad students who do that.

41:21 So we have assistants and colleagues, right? Right. We are fundraisers. We spend our time writing grants, rewriting grants, reviewing other people's grants, writing papers, reviewing papers, getting back comments from our papers, and revising those papers. We are at the computer doing this, and a big part of the job is getting money, and the NIH funding stream is very, very tight. Bill money has the NIH budget hasn't really changed that much. It goes up a little bit, but it doesn't keep up with inflation.

42:01 And right now, if you're writing a new grant, the chances of getting that grant are 10%. Really right. And it's a lot of work to do these grants. It's your whole life. It's unbelievable. And then when you get better comments, the comments sometimes are very helpful. Sometimes the comments are absurd and you can't respond to them like you would respond in a review and say XY and Z. This is not correct. You have to wait for the next cycle, next grant cycle. So you got to be you write a grant, you get a rejection, and then it's a year later that you're writing seconds.

42:34 It's interesting. I've submitted occasional papers to medical journals, and occasionally the reviewers give me these absurd comments that are almost impossible to discuss or debate. So it sounds like you have a similar problem with funding. But at least you can. You can write, you can revise the paper, right. And it goes right back in. Not for the NIH, You have to address the comments, but wait for the next cycle to yeah. So we have some funding from the NIH and we have some funding from private donors interested in pans.

43:13 And I work on a disease called Lowe's syndrome, which is very rare, and I've gotten funding from the Lowe's Syndrome Association to do this research. You know, you can't. It's very hard to get money for rare diseases. Well, if there are any people in the audience with any of these conditions that are interested in helping fund Doctor Lackman, please contact them Now I understand that in addition to all this research and writing grants and typing away, you also do a lot of teaching at the Albert Einstein.

43:42 Yeah, I do. I do a lot of teaching. Yeah. So I teach Human Genetics to the Med students. We just finished our session. Incoming students, graduate students, public health students, neuroscience students and psychiatry residents. So I do I have a lot of very active teaching load so that's. But I, I, I, I I enjoy that so that that's OK and then we have administrative things to deal with. I see patients a few days a month, so that's I'm really at my desk from 6:00 to 7:00 AM, until 7:00 or 8:00 PM with a break, meals, my wife and working out.

44:24 It's a full time. It's a really a full time job Monday, Sunday through Monday. Seven days. It really is, yeah. But it's not work because it's, you know, it's great stuff. Yeah, if you're enjoying it, it's kind of like a hobby. To be a scientist now is just incredible. There's so many, there's so many tools. You can do so much. It's really incredibly exciting. I envy the students who come here now. Are students now as as motivated as as we were years ago? Do they have different interests? What? What's your thinking on that?

44:59 Well, right now there are very few medical students who are doing what I did, which is to do train the medicine, do a post doctoral fellowship, or get a PhD and going to research. People who are going to research are MD PhD students. I see strict MD students are not going to research and a a major reason for that is the cost of medical education which is which is astronomical and much higher than when we went to school. So they want to just get through it and get finished their residencies and and make money and not train anymore.

45:32 So there are very few dot MD's, strict MD's who are doing basic. Research, so they go into clinical. They do clinical work on clinical research, right? Or they get MD, pH, DS, which really weren't available in in our day. Right. And they do, they take that, Even those students, many of them go into medicine. And the students, you know, I mean like they're idealistic, they are, are energetic, especially the first month. I mean it's just, you know, it's really great to see a full class, right by the end of a few months, you see nobody's there.

46:05 They just watch slideshows at the leisure, but at the beginning they're all attentive and. They're all there, yeah. So it's fun to be with them. Great. Well, it's been a very fascinating discussion. We learned a lot about genetics, psychiatric disorders associated with genetics, and some new STEM. Cells CRISPR. We covered everything. We pretty much covered everything. The Knicks and the Giants and right, literally everything. So alright. Well, thanks very much for coming today. I really appreciate it.

46:34 It's great to see you. Alright, great to see you too. Take care. Very good.