February Special - Episode#19 Cannabinoids – Dr. Allyn Howlett

Dr. Barkha Yadav-Samudrala: 0:06

Hello everyone on another episode of Nerdrx podcast and I'm your host Bob calm. And today is another monthly special episode and I am honestly a little nervous today but I have not been actually in cannabis field for a long time. But today we are going to talk about cannabinoids and who better to talk about it. Then the scientist who actually discovered the CB one receptor. Let's hear it from Dr. Allyn Howlett. For today's episode. Welcome Dr. Howlett to the show. And it's been an absolute honor, that you are here with us today.

Dr. Allyn Howlett: 0:50

Well, I want to thank you for inviting me, I do like to talk to people about what I know and what what we might be able to discuss about it.

Dr. Barkha Yadav-Samudrala: 1:02

Absolutely. And so let's talk from the beginning, about your background and how everything got started for you.

Dr. Allyn Howlett: 1:15

Well, I think I was probably a teenager, and I realized that I really wanted to know a little bit more about how the brain worked. I thought that was exciting. And at that time, there weren't any what you would call graduate programs in neuroscience. And I went to college, I was very fortunate to have what we now call mentorship. Back in those days, you didn't really get a mentor, but I had an uncle who was getting a PhD. And so I knew what a PhD scientist was in what they did. And he advised me that if I liked biochemistry, and I liked biology, and I liked chemistry, that Penn State had a good biochemistry program. So I applied and I got in for college. But at the time, there wasn't anybody there that was really interested in how the brain worked. It was an agriculture and engineering school, but I got a very good background. It's sort of stumbled along at first because my high school advisor, the guidance counselor, was really afraid that coming as a big fish in a little pool, and going to a big pool, that, that, you know, somebody from a small, a small, high school wouldn't, wouldn't have the skill set. But so he advised me not to take any math courses. Now that sounds kind of stupid, doesn't it? But But nevertheless, after about a semester, I realized that, you know, that that was a ridiculous idea. And so I switched my major from psychology into biochemistry. And, and, and got a degree in biochemistry, which I'm very happy with, because I think that that, that provides a very strong background for studying almost any kind of organ system in the body. So I went to graduate school, and I went to Rutgers, and I didn't know what pharmacology was at the time. So I had applied to the graduate program in biochemistry. And they gave me you know, a first temporary advisor, who was in the pharmacology department. So when I found out what pharmacology was the study of how physiology could be applied to therapeutics, I thought, you know, that's really what I'm interested in. So, so I moved into the pharmacology department instead and got my PhD in pharmacology. And I had had a little bit of experience as an undergraduate in cell culture. And back in those days, cell culture wasn't what it is today. Today, you can buy the media and already made and you can buy the plastic ware and it's disposable, but back in those days, so every single amino acid that we had in our media we had to weigh out and make the media for and we used a glass bottles that had been used for tuberculosis testing, because there wasn't any real plastic ware. And we had to soak our our glass in EDTA because that would get the heavy metals there. It leached out of borosilicate glass so that you could grow, grow cultured cells on. Anyway, that was the state of the art at that point. And so when I wanted to do my postdoc, I wanted to do it in a cell culture area, because I thought that was really the best way to study cell biology in the future. So, at that point, I looked to see in the research literature, the kind of exciting labs that were going on, and I found out Gilman was starting a lab, he had just finished his postdoc at the NIH. And he had some very interesting looking, cultured neurons that he had published on at when he was at the NIH. So I applied to, to do a postdoc with him. And when I got there, he wasn't so interested in brain cells anymore. He had discovered that there was a lymphoma cell that he was able to get from University of San Francisco that didn't respond to epinephrine to make cyclic a&p. And he assumed that it was because it didn't have the identical cyclists. So they call it psych minus. But we really needed to prove that. And his question was so fundamental. The question had to do with whether all of the receptors were the word worthy Danilo cyclases. So there were lots of identical cyclases associated, and were actually the receptors, or whether the receptors had to coupled to different proteins. And it was the same at dental cyclize. Now, you may think this is this over simplified view at the time, but but that was a state that it was in. And what we discovered was, after all, that the cells could respond to prostaglandins. So they must have an additional cyclase. But we figured there was something missing. So the long and the short of it was, in my three years of postdoc work, I was part of the team that discovered the G proteins. So if you looked up in the research literature, under G proteins, you'd never find those original papers, because, of course, we didn't call it G proteins back then. But it was called the G slash F factor. Because, you know, we weren't even sure that it was a protein so. So it was called a factor. And it was called F, as well as G G, because you could add GTP analogues, that would stimulate it, and F because you could stimulate it with fluoride. So that was the name that it had for just a very short period of time, before it was concluded to be the G protein a protein. So when I went to do my first job, which was at St. Louis University School of Medicine, in the department of pharmacology, I took those neuronal cells that I'd wanted to work with in first place with me, and started studying the prostaglandins. And the question, of course, at that point was, why would neuronal cells need to respond to prostaglandins? Because at that point, the prostaglandins had been involved in other areas, mostly to do with immunology, because blocking prostaglandin synthesis with non steroidal anti inflammatory agents was, was a well understood now. mechanism for pain relief. So it was at that point when I was studying prostaglandins that I came across a paper by some chemists at Pfizer. And Pfizer had noted that the active metabolite of Delta nine THC, which has a hydroxyl group and the methyl that's at the nine position, that that was a very good pain reliever in their pain relief, animal studies. And they had developed a number of analogs and had taken at least one of them into clinical trials. And then the drug company realized that the more powerful or more potent compounds they made, the more potent it was at the unwanted side effects. Their goal had been to have an at home analgesic that people could be using for what we now call neuropathic pain. And they were not able to send people home with the the sun I'd effects of sedation and muddled thinking and loss of short term memory that we recognize as being part of the cannabinoid response. And since they couldn't really ever separate those unwanted side effects, they consider those side effects to be a liability for sending people home with an analgesic. So they dropped the project. But the chemists at the same time said to themselves, well, you know what, those compounds that we have are a 20 carbon structure. And they don't have very many, they don't have any nitrogens. And they've only got a couple of hydroxyls. And, and they seem to resemble in their gross structure, what a prostaglandin looks like. So they had one very short paper in which they proposed without any evidence, they proposed that their compounds were working as antagonists, at the prostaglandin receptors that were in the brain. So I just jumped on that I thought, wouldn't it be nice to have an antagonist so that we wouldn't have to use non steroidal anti inflammatory agents as painkillers. So I wrote to them and and said that I had a single cell culture model system that I could test their hypothesis about prostaglandin receptors. And they were good enough to be able to not only send me their, their compound, which had been produced for, for human consumption. But it was really a pro drug, it needed the liver to deacetylated. And so they sent me the deacetylated form. And they sent me both an active isomer and an inactive isomer. So they sent me more than what I'd asked for. And I looked at it and with the hypothesis, that the cannabinoid pain relievers that they were looking at, were working by blocking the prostaglandin receptors in the brain cells. But that wasn't supported by our data. On the other hand, our data looked like it was non competitive inhibition. And that would make it a little bit more like what we were seeing with the opioid receptors, and with muscarinic receptors that people were beginning to publish, that they reduced cyclic a&p production. So so taking it from there, we had a cell culture model system of neurons that we could could study the inhibition of adenylate cyclase, as the activity of whatever these cannabinoid like painkillers we're doing. So I wrote back to the the folks at Pfizer, and by that time, of course, Pfizer had dropped their analgesic project. But the chemists still had the compounds that they'd all made so so I was invited to come out and talk to them. And they sent me home with a list of compounds to request from Pfizer. And, and they sent me all those compounds, so we could do structure activity relationships, and compare them to the painkilling activities that Pfizer had done. So the long and short of it was that was how I put my career together. So I would be in a actually good position to study a little bit about how the brain worked. And that really narrowed it down to how cannabinoid receptors worked in the brain.

Dr. Barkha Yadav-Samudrala: 13:48

Wow, I am so surprised about your collaboration with Pfizer, because you don't hear this now. So how do you think like this collaboration has changed over the years?

Dr. Allyn Howlett: 14:04

I think it was that I was working with them before the bye doll act encouraged universities and research institutes to be able to use intellectual property to protect their their research activities. Because once that happened, then all of the universities developed offices that would be available to patent their products and to protect their intellectual property. And so at that point, we began having to use agreements when we wanted to use other people's reagents. If you know right up until that point, if anybody asked me about out my cell lines, I could just send them the cells without having any, any paperwork to have to be done. And of course before that, that that was a period of time when we really didn't have the many activities that we do now with exchanging proteins and transcripts. But all of that now either has to come under some common law, legal arrangement or, or has to be a legal agreement. And I think that was when pharmaceutical companies really stopped providing materials to researchers just for asking. But back in those days, all I needed to do was write them a letter, tell them a little bit about what my research was, and ask them for the compounds that I would need to have to that that came from their drug company portfolio. And then, of course, the fact that Pfizer was no longer going to be considering these compounds, for taking them all the way through the pipeline. Of course, that was that was a major benefit to researchers. Because, you know, Pfizer gave me their compounds, but they also gave them to Billy Martin, who was doing animal work, and to any other researcher that had that would ask for them. So for most of our early studies, we were using Pfizer compounds that they had given us right up until about 10 years afterwards, and and then we couldn't get compounds from Pfizer anymore.

Dr. Barkha Yadav-Samudrala: 16:57

Okay, so I know, everyone knows you with the discovery of CB one receptor, but you have also developed the radio like and binding assay. And so was it around the same time as the CB one?

Dr. Allyn Howlett: 17:18

Oh, yes, that that really defined a receptor. In those days, receptors were defined pharmacologically. And so, you know, the example is beta adrenergic receptors compared with alpha adrenergic receptors. And, and so you could use pharmacological tools that could let's say propranolol could block beta receptors, but did not block Alpha receptors. So those were the tools that we could use to define what a receptor was. At that point, we could do structure activity relationships, because we had an assay that we could use for the cell signaling. But we really didn't have a protein. And the only way to identify a protein, or the best way to identify proteins back then, was to use radioactive logjams that could bind to those proteins. So that was a time in which Solomon Snyder was defining opioid receptors using radio labeled opioids. And the Gilman lab was defining the adrenergic receptors by using IODE nated adrenergic analogs. So the radio lag and binding assay was something that I was doing all the time in my postdoc. And so it was really the obvious choice for being able to clarify that the biological actions of cannabinoids were really resulting from a receptor that was a protein. Because at that point in time, the general idea was that these were very lipid soluble compounds, they might be acting more like general anesthetic anesthetics, getting into the membranes, changing the membrane fluidity and altering properties of maybe ion channels that were in neurons. So with that kind of an attitude, you really needed to be very specific and getting the the correct information that could support the hypothesis that it was really a receptor protein. So so even though we had our receptor that behaved pharmacologically that we could identify, we knew that it responded well to THC, it responded well to a good structure activity program from the Pfizer compounds, but we needed the radioactive compound. So, so again, working with Pfizer, Pfizer, before they had dropped the project needed to have the full aadmi information that means absorption, distribution, metabolism, and elimination profile in order to, to fully do clinical trials and people. So, so they had a plan already for radio labeling, one of their most potent compounds that they were planning had planned to take through the pipeline for marketing. So, but they weren't going to radio label it anymore, because they didn't need it, because the program had been just dismantled. So, so they gave the precursor to me. And I sent it to New England nuclear, which has changed hands several times. But it's DuPont now for radio labeling. And so they sent me a radio labeled compound. And we we did, we did all of the description of the binding, the kinetics and the the SAR that that was necessary to really distinguish that the biological activity that we had followed the same SAR as the binding to this radio label compound. So that really defined the receptor. And, and the assay, then radio labeled ly GaNS were just beginning to be very popular for doing like and binding assays. So New England nuclear, continued to use that compound, and they put it in their, in their catalogue. They, they told me that since I'd originally paid to have it done that, that they would provide it to me free, but you know, after after they changed hands a couple of times that kind of disappeared. But this was all before the days where you could recognize proteins on SDS page gels using western blots. So you know, things have changed since then. And we don't use radio logjam binding assays nearly as much, but we learned a lot, because we could truly demonstrate that, that even though we required G proteins for the inhibition of adenylate cyclase, we could demonstrate that the ligand binding assay required responded to the GTP analogs as well. So we we really could identify the physiological properties and the biochemical properties using this assay. It has could anyone else around the world who, who, you know wanted to buy though the lie gowns? Because now they were available?

Dr. Barkha Yadav-Samudrala: 23:45

Right. The next question I have is actually from my PI. I told her that I'm interviewing you and she got really excited. And she wanted me to ask you this. Do you think that we will ever see CB three and C before receptors?

Dr. Allyn Howlett: 24:06

I think some people think we already have. And for 20 years, I was part of the International Union of pharmacology nomenclature committee. And the there's a committee that has been assigned to virtually all of the G protein coupled receptors, and then gone on to all of the various ion channel receptors, and a very nice, Li presented database that is now run from the British pharmacological society and the International Union of pharmacology, and you can get information on virtually all the receptors that you could possibly think of based on this, but, but we had nomenclature committee for the Canadian artists chapters. And at that point, we knew that we know what the sequences were from the fact that that some orphan clones had been identified using this radio lag and binding assay that that I had told you about. So, so now that we had a CB one and a CB two receptor, and, and they were only about 40%, identical as far as the amino acid residues, but of course, they were forming a pattern, and could both bind the same radio like GaNS. Now that there can be a blessing. But then the pharmacology with the tools that we had at the time, THC and all of the cannabinoids had the same SAR with both CB one and the CB two. So it wasn't going to be so easy to separate those two pharmacologically until several years later, when pharmaceutical companies took a major interest in CB two receptors, and started using different kinds of structures. And the other aspect is the development or the announcement that overall high throughput screening, the Sanofi company had had found that there was an antagonist for CB one receptors. Up until then, the pharmacological separation of those two receptors was very difficult because the agonists were all acting at both of those receptors. So once we had a pharmacological antagonists that was very specific for CB one, and then the company found another one that was similar in structure but but different and much more selective for CB two, then we could really separate those two. However, your question is about potential others. And the nomenclature committee was very hesitant to, to identify something like GPR 55, for example, as being a cannabinoid receptor because it didn't follow those same patterns, it didn't respond very well to cannabinoid compounds, even though some cannabinoid compounds could bind to the receptor and appear to be antagonists. So so the feeling at the time was that we called them cannabinoid receptors, because we didn't at the time, know what the endogenous ly GaNS were. And, and that we should begin to think in terms of what that orthosteric ligand binding site really responded to. So it was felt that, that something like GPR, 55, was, was not fulfilling some of that criteria. And then the information came through that the GPR 55, was really binding into another set of lipids all together. And there were other International Union of pharmacology committees that were studying those kinds of receptors. And so, so we felt that trying to claim GPR 55 as a cannabinoid receptor was not really appropriate because it fell better under the categories for some of the other lipid mediators that that that we're becoming available. So, you know, I think having CB one so abundant throughout the brain, and not seeing alternative receptors that could be identified pharmacologically is very unusual. And I would contrast that with maybe something that's an extreme opposite like serotonergic receptors, where you have maybe 13 or 14 Now identifiable receptors based on pharmacological Lagann specificity. And there is none that has come up from the cannabinoid field in this in the brain where you would really like to see some separation of the side effects from the beneficial effects. It would be very nice if you could separate sedation and muddled thinking and loss of short term memory and coordination from pain relief, because that way you could promote compounds that could be cannabinoid receptor mediated pain relief, and maybe use them in combination with non steroidal anti inflammatories or in combination with opioids. But right now, it looks like that receptor has been so highly conserved throughout all areas of the brain. And when you stop to think about it, what is it therefore, it's there to modulate neurotransmission. And it modulates it the same way with the glutamatergic excitatory receptors and release of glutamate, as it does with the GABA ergic inhibitory receptors. It's the same endocannabinoid release mechanism that alters the ability to to release the neurotransmitter from the the storage vesicles. So using that same mechanism throughout the entire brain, if you were to modify that, and have CP threes, and C befores, and CP fives, maybe that wouldn't be so efficient away as the modulation that takes place now. And the reason is that we've got a multitude of different kinds of responders to glutamate. So we have a lot of opportunities for changing both ionotropic glutamate receptors as well as the number of metabotropic glutamate receptors. Well, with that in mind, you maintain the cannabinoid receptor regulation of neurotransmission, the same way for all of these receptors, but those receptors are the ones that have been modified throughout the brain. So maybe that's why you don't see a variety of receptors that are going to be responding the same way that that these do.

Dr. Barkha Yadav-Samudrala: 32:14

Okay, wow. So in your opinion, what do you see, the future of cannabis is? And do you think it will ever replace opioids?

Dr. Allyn Howlett: 32:34

I think that a lot of people are looking for good pain relievers. And right now, they're not finding what they really need. And part of that is the addiction properties. Part of it is that pain is not really pain. There are lots of different reasons for pain, causes for pain, and responses to pain. And so I think pharmaceutical companies are beginning to identify some other alternative pathways that that that can be modified, but certainly the cannabinoids have been used for pain relief for centuries, maybe millennia. And, and would be good choices. With that in mind, I think people are using whatever cannabis products they can get for their pain relief. But there's still, you know, unknowns, we know very little about what CBD is doing or how it works. And THC has those side effects. And while it's a different side effect profile than the opioids, that's why I'm suggesting maybe a dual combination medicine might might be even better, because then you would reduce the the different side effects that the two different kinds of drugs would have. So you know, that is one opportunity that I think we have available for producing better pain relieving combination compounds. But what researchers are looking for now, I think, is more specificity, something that could affect maybe only those neurons in the brain that are already responding by releasing endocannabinoids at their neurotransmitters, sites, and so beginning to look at the endocannabinoid system, modifying the rates of synthesis or the rates of degradation of the endocannabinoids That's that's really got a good deal of promise towards modifying cannabinoid actions in the future. And I think the other one is modifying the signal transduction. And that's what my lab has attempted to do for many years is to determine if there's a way that we could single out one of the subtypes of Gi as being predominant in one area of the brain. And now we're beginning to look at some of the associated proteins and how they are affecting the cannabinoid receptor. So of course, one of those that you look at is the beta reston's. And we really don't know enough about what kinds of therapeutic opportunities we could have through G protein coupled receptors versus beta reston's, but that's one way of looking at it. But another way of looking at it is to look at the other kinds of proteins that are binding to the cannabinoid receptor and asking about how they work. And so we've been looking at cannabinoid receptor interacting protein, and how that interacts with the G protein signaling.

Dr. Barkha Yadav-Samudrala: 36:14

So that has to do with the bias. The bias signal, yeah,

Dr. Allyn Howlett: 36:18

yes, people? Yeah, people would call that biased agonism if we can get something that is important for regulating in one set of neurons in the brain, but don't affect the other sets of neurons that may be involved in memory or in cognitive function.

Dr. Barkha Yadav-Samudrala: 36:41

Okay. So, you know, like you mentioned, people have been using cannabis for like, even though not in an intended way, but you know, as a pain reliever and cancer patients, HIV patients, and still THC and CBD falls under schedule one. And cocaine, which I don't think has any therapeutic use is still scheduled to do you think it's gonna change over time?

Dr. Allyn Howlett: 37:20

Well, Marinol is delta nine THC. And that is scheduled to, but it's synthetic, which is to say that it's not extracted from plants. And I think that was one reason that the FDA approved it in 1985. They also approved it in 1985, because it was the only drug available at the time that could block the nausea and vomiting of cancer chemotherapy. But, you know, other compounds have been made available after that. In that era of time, it was also approved for use in what we call Caixa, that's body wasting in the diseases that were part of AIDS. Because back in those days, if if you became HIV positive, the virus in inevitably broke down your immune system so that you couldn't fight off any cancers or other diseases that were immune suppressed. So So it became a very useful drug, not only for pain relief and in the cancer, but for reducing the, the vomiting and and also increasing the appetite so that you could gain body strength. So, you know, that was the situation in 1985. And it was packaged and sesame oil in a capsule, which it still is, but now it's also available in a liquid form that could be swallowed. But it always occurred to me that if you were if you were vomiting due to cancer, chemotherapy, that taking an oral medication that doesn't dissolve or doesn't get absorbed very reliably, may not be the best route of administration. So I think at this point, pharmaceutics needs to step in, and I'm sure that there are drug companies now that are very interested in how we can get lipid soluble compounds to become more bioavailable. And I think that's, that's going to be very useful. But I think the situation now has, has come to the point where we have one legitimate drug in it In the United States that has come from grown cannabis and that came from GW Pharmaceuticals Epidiolex because the Food and Drug Administration's has not yet approved the Sativex which has the THC in combination with the CBD for, you know, the those compounds, although it is available for clinical trials. So we have many clinical trials now using Marinol. And I think with better pharmaceutics helping to get a more reliable THC kind of preparation that, that those compounds can can be submitted to the NIH, the Food and Drug Administration so that they can become legitimate drugs in America just like they may be in other other areas of the world.

Dr. Barkha Yadav-Samudrala: 41:03

Okay. So this is this question is not regarding cannabis. But just as a scientist in general. How was it being a woman in science back in 70s? And 80s? And do you think things have changed now?

Dr. Allyn Howlett: 41:26

I'm certainly we have a lot more women in science, because back when I was starting out, I think most women felt that they had to make a choice. You could either get married and have a family, or you could have a career. And to my mind, you know, I I didn't want to have to make a choice. It seemed to me that I had to be able to do both. But yeah, I think you have to really organize your time so much. So much more so than then most men do. Because you know, family responsibilities. Back in those days were really very gender divided. And, and there weren't a lot of backup facilities. But I, my baby was born, I only had one child. And and of course, that makes it handier because it's a lot easier to, to manage a family of one child than it is to manage a family of more. But I was very fortunate and having a wonderful daycare center. And I really felt that, that the curriculum that daycare centers have developed now for early learning is so much more advanced now than what we had before. But so much early childhood education is something that mothers at home, really haven't had any training and don't have so much appreciation for but but I can see now that so much socializing takes place in the very early childhood days. And I have no regrets about having had a child that was educated in in a daycare facility because she had a wonderful socialization. Prior to beginning, what would be the standard first year of schooling and kindergarten. So so, you know, I think that's an area that has advanced, there's still work to do on that. I think I was very surprised when I went to give a seminar when my daughter was maybe four years old. And I went to a school that I knew didn't have a large budget for seminars. And back in those days, your airline fee depended on where when you when you flew and and if you stayed over a weekend, so I told them that if they invited me for the Thanksgiving weekend that I could arrange airlines so that it would be over a weekend and and that saved them quite a bit of money. So but what it meant was I had to bring my daughter with me to to the seminar. So usually what I would do is call the hotel and get their bonded babysitting service. However, they said to me, Well, we run the daycare center at the University so so you can just call them, I was just shocked, because I didn't realize that and maybe there weren't very many of these, I'm sure it was a new thing. But they had a daycare center, that was like a drop off daycare center, which is perfect for university center. Because, you know, when you're a student, you may have morning classes, but not afternoon classes. So you don't need to pay for a whole day of, of childcare if you only need childcare in the morning. But more importantly, the daycare center stayed open till nine o'clock because they had people with evening classes. So, you know, I'd like to see more of these here. And the other aspect that I had one experience with was a sick care daycare center for when, when my daughter had chickenpox, because you can't send a child back to regular school until maybe two weeks after, but you know, they start feeling much better after two days. So this was a facility that was started by pediatric nurses. And they had a chicken pox room that was separated. And then they had a room for kids that had broken arms or legs or something like that, and weren't quite ready to go back to school. So, you know, these are the kinds of facilities that I think we still need to have developed at at many places, even though we have much, much better early childhood education. And we need to start being more grateful for the work that our early childhood educators do. And, and let them know how much we appreciate them.

Dr. Barkha Yadav-Samudrala: 46:51

Absolutely.

Dr. Allyn Howlett: 46:52

So I think that's that's one thing. That that are, that has really changed that has has become much more helpful is the availability of good, good early childhood education.

Dr. Barkha Yadav-Samudrala: 47:07

Yeah, I cannot imagine being so carefree without the daycare we use for my twins, like they are absolutely outstanding. So this is one question which I ask all my guests and here it is, what is one question you would like to get answered in your lifetime?

Dr. Allyn Howlett: 47:37

Oh, dear. Well, at this point, in my lifetime, I have really reduced my laboratory activities to just specific questions about the cannabinoid receptor. And I think there is still a lot to be learned simply because it has great importance in not only the brain but other organ systems in the body. So I think there is more than one question to be asked and answered. And what we really need is people who have expertise in a wide variety of organ systems that come forward and say, Well, I wonder what the endocannabinoid system is doing. And in my disease state, so I think we have broad questions that need to be answered, but maybe not answered by me.

Dr. Barkha Yadav-Samudrala: 48:53

Okay, and my final question, what advice would you give to young scientists who are just starting in the field like myself?

Dr. Allyn Howlett: 49:10

I think time management is something that you really need to pay a good deal of attention to, because of, of the various roles that women play in, in the family as well as in, in the in the career management. And I think many people haven't quite figured that out and going to college. You never figure it out. Because you know, people tend to have their very loose time management when they go to college. But once you get into graduate school, you really have to start organizing, organizing your time prioritizing what's important, making sure you get done efficiently, and then go on to whatever the next phase is. And if I had to go even further to give advice on how one might be able to do that, when my daughter was in school, I volunteered for activities that could serve a dual purpose. So, for example, when I was I was with the a group of parents that put together what we call the school district Science Advisory Council. Now, the school district hadn't asked us for our advice, but but we knew that the school district needed advice on how, how science should be taught hands on science activities for kids, training the teachers. And so, so that was one of the primary activities that that I participated in. And by dual purpose, I mean, not only did it provide a great deal of importance to the schools, that that my daughter was going to, because our science advisory council helped out with all the science fairs and helping the kids find tutors so that they could all do science projects. But also, I could put that on my, my CV and let my university know that, that this very important activity was taking place in the community, and that I was representing the University and getting this done. So so it covered both activities, were community service activities that my university would find happy, would would be happy to have me do, but also the community activities that that I think all parents really want to be involved in some activities in their in their children's lifespan. So that's, that's one way of, of organizing things so that you can do something that's a value to both your career and your children. And the other aspect of that is that usually, when I went to very large meetings, I didn't take my daughter with me, but But I belong to the international cannabinoid Research Society and and that's a small meeting. And it's always been located at places that were family friendly. And so my daughter got the advantage of going with me. And of course, I usually had to bring my own babysitters. But nevertheless, she got to see places all over the world largely because she could go with me to meetings such as this. And I think she attended more international cannabinoid receptor meetings than most of the membership itself did so. So you know, I think she went to some kinds of meetings with me like the school board meetings. She said to me one day, Mommy, I don't like those go to school board meetings. And I said, why? She said, Well, they don't serve cookies. So, um, you know, she got to see what a working mother did. Yeah. And she was always very well behaved and, and knew when she had to start acting like an adult. And so I think having that kind of role model has has really put her in a position to be very secure in her own career herself.

Dr. Barkha Yadav-Samudrala: 53:57

Wow. Well, I think thank you so much, Dr. Khalid, this was absolutely mind blowing. And it was such a great honor talking with you today. And thank you so much.

Dr. Allyn Howlett: 54:15

And thank you for inviting me,

Dr. Barkha Yadav-Samudrala: 54:17

of course. And listeners. I hope you enjoyed this episode. And, as always, I will catch you next week on another episode. And in the meantime, if you have any suggestions, please email me at Barkha at Nerdrx podcast.com. And remember, it's good to be a nerd bye