1_12 Sisi Li: Epigenetics of Trauma, Psychedelic Patent Wars, and Healing the Scars of Covid as Chinese Americans

Today my guest is Sisi Li, the Senior Data Architect Lead at Porta Sophia, a non-profit online library for innovators and patent examiners to find relevant prior art in the field of psychedelics. She has a B.Sc in molecular and cellular biology and psychology from the University of Illinois, and a Ph.D. in Neuroscience from the University of Wisconsin. Her doctoral research focused on the epigenetic and molecular mechanisms underlying depression and anxiety disorders. Sisi was previously a  Research Scientist at Gregor Diagnostics, a prostate cancer diagnostics startup. She co-founded the BioForward Woman in Biohealth (WiB) mentoring program and is on the WiB steering committee. Sisi is passionate about creating more connections among women in the biohealth community.

Connect with Sisi Li at https://www.linkedin.com/in/sisiliphd.

Transcript

 [00:00:53] RS: I was mentioning to you before we started recording that there's so many things I want to hit and I wanna make sure we can talk about them, cuz it's super exciting, very relevant. But before we get into that stuff let's start at the very beginning. How I like these conversations to happen with my guests is, I really want to know, how they grew up, what makes them who they are, these formative experiences that we tend to have, whether it's like growing up in different parts of the world, what we studied, the books we read, our upbringing and things like that. 

[00:01:19] So with that, you moved to the US when you were 10 years old. I think that's a very particular stage of life, right? It's not like when you're moving to the US we are five years old, you don't really have many memories or a developed sense of self. But at 10 years old you probably have memories from Beijing already. So I'm curious, having a hyphenated identity, what were your earliest memories moving from Beijing to the US and how do you identify now? 

[00:01:46] SL: Great question. I definitely remember my early memories of moving to the US. It was pretty profound change in my life. As you said, I moved to the US when I was 10. I was actually raised by my grandparents in Beijing, China.

[00:01:58] But my mom two years before I moved, so when I was eight, my mom had actually moved to the us to follow her dreams in doing research at Northwestern University. So at 10 years old I came to Chicago in the US and we had never talked about immigrating before she moved, so it was a pretty sudden change.

[00:02:17] And honestly the biggest challenge, was probably the language barrier and the culture barrier. At 10 years old and also in, in Chinese culture, be a good kid is really like being obedient, and getting good grades. Which is a very different from culturally what is be a good kid in the United States is.

[00:02:33] So I came here biggest barrier was language and not really being able to speak to anyone, not really having friends aside from my family. And then, I remember going to school a week after I had come to the US and finally gotten over the jet lag from that 13 hour difference. And then it was a Friday, I had worn my favorite dress. We went to the school I was gonna attend. My mom and I had thought I was just gonna, register to be a student and then start the following week. But before I knew it, like they just took me away and put me in class right away.

[00:03:04] And it was really disorienting just as as a child who had just come to a different country, I didn't speak the language. I had honestly never been near anyone who was not my race or who didnt speak my language ever before then. Cause as China is a very homogenous population. Really just Chinese people mainly.

[00:03:21] And it was very disorienting and I remember going through the day just not really knowing what going on I was just put to sit here in the classroom look this way. And then it was lunchtime and then we had PE class and I didn't have a gym uniform. So it was really like, I would say lowkey, traumatizing to be there in my favorite dress. And then it was not my favorite dress after that anymore, definitely. But just that, that like disorienting feeling of not knowing was really hard. And then I remember reuniting with my mom at the end of the day, and then she was like, I'm so sorry, I didn't know this was gonna happen. I didn't know you were gonna start right away.

[00:03:57] And then I also believed her. It was the first realization that, my mom didn't know, always know what was gonna happen. And then I kind had to like, figure stuff out myself. That was really the first introduction of that idea of I might be learning things that my mom wouldnt know and just having to figure things out.

[00:04:16] RS: So your mom was already in the US and when you had moved, who did you move with? Did your mom go back and get you?

[00:04:23] SL: So I had moved to the US with my grandparents.

[00:04:26] She came two years before I did to work at Northwestern University. So it was my maternal grandparents, my Nina Yaya came with me. And then we all, looked together in a one bedroom apartment in downtown Chicago for the first year. Just so they helped me like adjust to American culture and then they left after a year, and then it was just me and my mom from them.

[00:04:48] RS: So what was it like for your grandparents? were they familiar with Western culture and American culture by then, or was it new for them as well? 

[00:04:55] SL: It was definitely new for them as well. I remember the phrase my grandparents learned, which was "no English" when anybody talked to them. And that was basically what happened with every interaction.

[00:05:07] RS: What did it feel like to see the US from their eyes? Cause you have a whole generational divide added on top of the fact that it's a very new culture. 

[00:05:15] SL: Looking at American culture from their eyes, I think it's a little bit different because they knew that they were going back to China and that China was their home.

[00:05:24] Whereas for my mom and I, we were coming to this place to start a new life, which was very different. So for them it was like there was really no, no pressure for, assimilation to, to understand, get used to things. They were just there to support family, which they did tremendously from my mom and I.

[00:05:40] But it's a very different perspective. 

[00:05:43] RS: Your mom went to the US to pursue research. Yes. And you in a way, followed her footsteps. So what compelled her to move to the US? 

[00:05:52] SL: So she was doing cancer research in in China, but she had worked with a visiting professor from Northwestern who was actually researching ALS and so like Lou Garrett's disease and she was really interested in this research and he had offered her an opportunity to come to the US to work with him. And then on the other side as well, I mentioned that my mom's a single mom. My parents had been separated in China when I was two.

[00:06:17] At the time in China, I think having a non-traditional family was really taboo and looked looked down upon. So that was another contributing factor to her wanting to move to a different country and to just, give me more opportunities, have a fresh start. Really just be her. 

[00:06:34] RS: Tell me a little bit about growing up with a single parent. What was that like? 

[00:06:37] SL: So I had, my grandparents were there with me before I was 10, and they I mean they are very loving and supportive even though they're some inter generational trauma that I'll talk about later with that.

[00:06:48] But I had really only met my dad once and it was right before leaving for China and he also, he has multiple sclerosis, so he has had MS basically all of my life. So it was a very, different experience, pretty disorienting meeting with my dad and then moving to the US.

[00:07:05] And then in the US once my grandparents left, it was really just my mom and I and I think I think I think children of immigrants oftentimes they grow up a bit faster because, when you're a child, you think your parents are of these omnipotent beings that if you're hungry, they give you food.

[00:07:19] If you're want anything, they provide it for you. They're all powerful. But then as an immigrant in a new country, I think you quickly realize that your parents might not know things and you're learning at the same time as your parents. But children have just such a faster ability to absorb, especially with language and learn. So I was finding myself learning things at the same rate and then eventually faster than my mom, especially when it comes to American culture. And so that was a, like a pretty quickly, a quick wake up call of I, I might need to like, figure things out.

[00:07:51] And my mom was incredible. She used to she worked in the lab and sometimes she would work weekends and night and then she would bring me with her cause we didn't have childcare. And then I would just hang in the

[00:08:08] RS: That's so cool. You made a really, actually a really interesting observation. I did not think of it that way before. And I wonder what that relationship could have been or tends to be when kids are actually older. So let's say if you moved there when you were 15 or 16 I can certainly imagine had I moved to Canada with my parents, I never moved when my parents, I came to Canada as a student, my parents are still back in Bangladesh. I think, that sort of curiosity, that tendency to grow together might be truer if you're younger versus like older. Because I think it's one thing to see your parents being equally vulnerable or learning or might not know everything, and to accept that but I wonder what I would've been like being the rebellious troublemaker at 15 and watching my dad not know something. I wonder how I would've reacted. No, but that's a really interesting perspective. So in terms of absorbing American culture and Western culture in, in ways faster than your mom, what are some of the first things you absorbed?

[00:09:05] SL: A distinct memory comes to mind where I think this was maybe sixth grade. We were, I was at a grocery store with my mom and we were checking out items. And then the grocery clerk had asked just very quickly, like paper plastic. Asked my mom that , and then she was like, frozen.

[00:09:21] She didn't know what to do, and then she looked at me and then he was like, paper plastic. And then I was like, paper . Yeah. But that was one of those things where it's I think it's common for, parents like immigrants who have a harder time learning languages, especially with accents too, to then look to their children who often don't have accents and to be able to translate some of those things.

[00:09:43] And I also wonder, 10 is a very different age as like 15. you've developed a lot more of your identity. So yeah. That's very 

[00:09:51] RS: interesting. What felt at most odd between the Chinese culture that you inherited and you grew up in until 10, and the sort of culture you're now forced to assimilate into.

[00:10:03] SL: I think a big difference is like the Chinese culture is very group oriented. It's very, very much like we are part of a group and then we, sacrifice for the greater good of the group and oftentimes the family unit. Whereas in America it's very, it's a very individualistic your own accomplishments type of culture.

[00:10:22] And I think that was a really big shift for me that, in China it was like I just obeyed my grandparents and I was a good kid and then get good grades. And then in, in America it was like I had to. Figure out, what was cool, like how, what is what is like cool in American culture and thinking for yourself is a very American concept that like really took a long time for me to really embody that.

[00:10:48] And there is also that pole, as you said, the hyphenated identity, the pole of the two cultures. I think when I was younger coming right after I came to America I, I went to school in the inter in the city of Chicago. So I was fortunate to be around all quite a bit of diversity.

[00:11:04] People from different races, different class and there was a lot of other immigrants. School, especially attending my English as a second language class. So I was exposed to a lot of that, but I also very quickly realized that the dominant white culture is the the culture to strive for.

[00:11:19] Like we were all there. But then the cool people the people in school, you even understand what high, lower status is. Are the, know, do dominant white culture people. And so hence starting the, process of assimilation into learning white culture. What is cool individualism, achievements those kind of things were valued much more than collectivism and.

[00:11:38] And working together. So that was, that consistently is still a pull. And even now, like I have spent my youth just, learning what is the best in American culture and then complying in it, achieving success in the sense I have been able to follow my dreams and work in psychedelics.

[00:11:54] And that is like very much not, Chinese culture. But now I find myself missing that part. There's a lot of respecting the elders, like philo piety, respect for your parents, to pay back that love. A lot of those things that are just, that I feel like I want to integrate those two aspects more.

[00:12:13] RS: That's really well said. And that's actually something I can deeply relate to. I think when people talk about collective identity or communism or whatever have you, I think it's still ... everything has good and bad, right? But I think the point you're trying to make is that where the individual ends, the community begins.

[00:12:29] And what that really means is that at what point does aspects of duty and obligation or responsibility, maybe not obligation, but I tend to think of in terms of like duty... what are the things that you opt into in terms of, I want to care for people, I want to care for my community. And that requires some level of sacrifice, requires level of humility, requires a level of selflessness that you need, right?

[00:12:52] To recognize that, the community is bigger than me. Yeah. So I think those are really important aspects. I'm curious because, you alluded to this already, which is you're already working in psychedelics, so in some ways you've chosen your own path. Now, do you think that the friction point between the sort of community identity or collective identity and the individualism, was that a little easier to reconcile because your mother being a single parent in facing the taboo that she faced in China, and still I'm sure as a single parent of being a woman, it's also is already difficult no matter where you are. Was that a little easier because your mom was like, no, screw it, do your own thing. Did that feel easier or was that still very frictious? 

[00:13:31] SL: I think you, you hit on a really good point. I think it does feel easier because I have felt different, with my mom being a single mom. Even in America, our Chinese friends, we have, most of them come from very traditional families.

[00:13:43] So I think there, there was always that sense of needing to, I don't know, prove myself that, just because my mom is a single mother, like her child can accomplish great things. And and then also I think it's, I don't know if this is part of just realizing it being in the environment or like my family telling me, but the sacrifices our parents make for our futures is very much in it's very much like in my awareness, Al always , and it's not even like I have to go down this particular career path cause of them, but just I have to, do my best.

[00:14:16] I have to strive because of them. 

[00:14:19] RS: Yeah. And I think that's a really interesting point too, cuz often I think, I get that a lot and my parents made incredible sacrifices, but the number of times my dad's I didn't have shoes when I was your age . And I'm like, okay, I get it, but do you prefer that I don't have shoes?

[00:14:33] And so there's this sort of push and pull, but ultimately I think the point you're making at least the way I'm hearing it is that, you have to do your best. Whatever it is you do with integrity, do the best that you can do and whatever that might be, whether it's art, science, performance, whatever, absolutely. So moving from that I want to come back to cuz your mom did, has a similar pursuit in sciences and research and cancer research. You focused your attention to neuroscience and particularly the neuroscience of how stress leads to psychiatric disorders, especially from the epigenetic perspective.

[00:15:06] Now this is, this feels super timely cuz stress and mental health is top of mind. I think stress is the silent killer everywhere, right? . And I think were at this point where it's trying to understand that stress is really at the root of all physiological and emotional issues for the lack of a better word. Now tell us a little bit about the work you are doing, particularly the connection to distress and psychiatric disorders, and then of course, where does epigenetics come in this and tell us what epigenetics is. What is it, what sort of insights did you gain from your work? 

[00:15:39] SL: So I will start with just my graduate work. I went to university of Wisconsin Madison for my PhD. And really, I've always been interested in mental health and how people cope with stress, different stressors, and how come some people with the same stressor can develop, PTSD while others have post-traumatic growth. What is the molecular mechanism underlying these? And as they say, a lot of, research is mesearch. I really just wanted to understand for myself. But I studied mostly in the animal models looking at looking at epigenetic factor. So what I mean by epigenetics is so we are our genetic blueprint are the DNA codes the nucleotides following each other. But that sort of lays out the blueprint for what gene expression and then downstream protein levels and then downstream behaviors that are associated with those.

[00:16:25] And so you can think of the genes themselves as like a switch being there and it could be switched on or off, and so expression or no expression. And then you can think of epigenetics, epi meaning on top as a modification that sort of sets the dial where you could have, higher or lower in this range of expression level.

[00:16:43] So it's one way of modifying gene expression without actually changing the basic genetic codes like mutations. And so what we know from epigenetics and with the marker that I study, is that it is it is susceptible to environmental factors, so environmental stressors and things can change epigenetic profiles so it can change how much gene expression happens.

[00:17:06] And so the particular marker that I studied was five hydroxy methazine. So it's a methyl group on top of the cine, the nucleotide cine, and then depending on how how many genes have this methyl group you can increase or decrease gene expression levels. And and because five hc the marker that I study unlike the more commonly just methazine is more susceptible to environmental factors.

[00:17:31] And that kind of gave me the hope of . If a bad stressor could cause, downstream and lasting epigenic effects and gene expression changes and behavior changes associated with the psychiatric disorders like depression, anxiety, or ptsd, then perhaps good environmental factors like exercise or meditation could also affect our nutrition, could affect these markers as well and maybe reverse the detriments that we see as well.

[00:17:57] And and your comment about stress being one of the main reasons of these psychiatric disorders we see, especially in the era of Covid, a tremendous stressor unprecedented especially frontline workers. You. Stress at a low level is actually really beneficial. When you think about stressors, like exercise puts stress on your body, but then you get benefits on the other side.

[00:18:19] Your body is actually very resilient and it's meant to deal with these acute stressors very effectively through the stress response, HPA access, it's activated, your body deals with it, stress's gone, and then you're all, you're back to normal. And it helps you deal with stressors like that better in the future.

[00:18:37] But the problem with a lot of these, stress-induced psychiatric disorders is that, it's constant and it, the stressor never goes away. So then your body adapts to this new norm. So when the stressor does go away, it's still adapting to this new norm. And so it doesn't, like your brain haven't quite caught up In the case of PTSD you think it the triggers are still there, but it's actually not physically there, but your brain is kinda stuck in that routine.

[00:19:04] Which, leads nicely to psychedelics. In terms of the things that we know about psychedelics and its ability for neuroplasticity to, to disintegrate the default mode network versus often associated with the psychiatric disorders. It can alter brain connectivity. So making the regions that don't normally speak to each other talk to each other again.

[00:19:22] So that's part of the know, the interesting thing about what psychedelic can do epigenetically. 

[00:19:26] RS: So lemme see if I got this correctly. You were studying the effect of persistent stressors on the, let's just say, conditional expression of particular genes, right? So in this particular case, what sort of persistent stressors were you studying? 

[00:19:47] SL: So I was mainly using animal models. And so we had two types. We had acute stress, which is just like a one time stressor.

[00:19:54] It could be like an electric shock or a four swim test or an animal odor, like a predator odor, a fox odor. Or the other type, which is very interesting is what we call the chronic variable stretch stress. So it's chronic over a long period of time, sometimes weeks for the mice that's pretty chronic.

[00:20:10] And then they're variable, they're all like low. Very low key stressors that do not do dark harm, such as like white noise at night, saturated wet bedding being separated or lights on when it's their dark period. So these are all like individually would not be very stressful and just, as much as you can imply from animal models these would be I would guess like the daily, things that come up that aren't like dangerous but are chronic and also variable.

[00:20:39] They're unpredictable. 

[00:20:40] RS: You just mentioned that in isolation, maybe an acute stressor could actually lead to resilience, but it's the persistence or persistent exposure to the stressor that could actually could lead to some sort of conditioning, which I guess PTSD is some form of conditioning where like even after the event is over, your brain and your mind is still conditioned to respond as if that stressor was still there.

[00:21:05] Where is the line between where an acute stressor becomes a persistent stressor in terms of how your mind models it. 

[00:21:12] SL: I think that depends on the individual. And then what amount of, maybe, perhaps stress they have experienced before. When I was in grad school, I went to this seminar that gave a really interesting concept called stress stress inoculation, like a stress vaccine where they would stress, I think this was primates, they would give very low stress, increasingly stress stressful stimulus to, to to the subject.

[00:21:34] And that they were much more able to regulate themselves. If they were stress inoculated, with the vaccine, like they knew what to do. But we're talking about, one time and then you have a pretty similar experience afterwards that you can recall upon that. But but I think what you're talking about with the chronic stress is never quite having, get back, getting back to the base level.

[00:21:55] And in the case of, PTSD with veterans, it is very adaptive at the time for them to respond and for your brain to respond in the way that it does. And, but it's just, it's harder for the brain when the stressor goes away, but you're still quite in, in it. And there are epigenetic changes that happens from that, that it's just harder to reset.

[00:22:16] RS: There's so many things I thinking about as you mentioned that word stress in inoculation, and I wonder. , what kind of social factors could be actually very effective Stress inocular leaders. I think about a year and a half ago while we were in the depth of a pandemic, there were these articles talking about oh, the mental health effect of pandemic is not as bad, but there's a nuance here,

[00:22:35] It's not as bad for people who actually have a sense of community, who feel that they're in a safe community with people, loved ones that they feel protected. It was the people without it that had the the most harmful experience, the most harmful effect, mental health effects of the pandemic. The thing that I'm thinking about is the sort of, in terms of stress inoculation, what are some of these social factors going back to again, they, which may have epigenetic expression that are very effective inoculator. So what are your, what's your thought on that? . 

[00:23:08] SL: I think having, community and social connection is huge for us humans in order to regulate.

[00:23:15] I think one of the one of the ways to lower cortisol level is, hug from another person is just like that face-to-face interaction. That's one of the ways where, we have evolutionarily, let's say we're, we're in the woods and then suddenly we see a predator and we're chased by it, the HPA access activate.

[00:23:32] We run, we finish we outrun the predator, and then we come back to our our cave with our home, our community, and that we. Safe. And so then, the cortisol levels decrease, oxytocin kicks in, and then we can, basically reset our nervous system to tell it now we're safe.

[00:23:48] Whereas, I think people, especially, what you said in the covid pandemic with those sort of strong bonds it's very very good far nervous system to come back, social interactions. 

[00:23:59] RS: Did you see some of the remediative effects of stress inoculation in any animal model studies?

[00:24:05] Because often I find we do these animal model studies to look at the impacts or the bad parts, but we don't look at what actually would cause, what would repair some of those. . 

[00:24:15] SL: I personally, I did not do look at that in my research, but it's something that I'm very interested in, exactly. I think a lot of academia really focuses on the the illnesses. And not as much on the other side of the spectrum, like positive psychology, how, how these things could strengthen our ways of coping. 

[00:24:33] RS: Yeah. There's this one example. I think, there's a very frequently sided example of oh, we gave rats in a cage.

[00:24:40] Cocaine water versus normal water, and they got addicted to cocaine, water, and all became, addicted to the cocaine water. But I think this was, and that's, that was supposed to prove something about human nature, where if you give people some sort of addictive thing, we'll all choose to be addicts.

[00:24:55] But the nuances, I think that researcher experiment was like disproven in its hypothesis because , they replicated the same experiment. But they also had this other like alternative, which is okay, we gave the same rats that were previously in this cage, but now we put them in what is equivalent to an amusement park.

[00:25:13] Lots of like social time, lot of interaction with other mice and rats and stuff like that. And then we gave them cocaine, water versus the normal water. Guess what? , they weren't addicted to cocaine water. Yeah, again, modeling what these studies are supposed to say about human nature. Cuz then of course we take the animal studies and say, oh, it was true for this sort of subset of animal models. So it must be true for human nature because there's some sort of syno, some sort of like overlap between the genetic code and things like that, right? . So I think it's so fascinating. Okay, so let's now move to, you touched on this briefly, is that psychedelics.

[00:25:48] Then create an opening, or at least, , propose another alternative to how the mind may work when faced with acute stressors or persistent stressors. What are some of those key findings that you that you saw? 

[00:26:01] SL: Sure. So before I get into the findings, I wanna just put out an analogy for how to think about this.

[00:26:07] In the case of let's say, a mental illness like depression a lot of the times you have rumination going on. You're just thinking the same negative self-talk. And you can think of it as a downhill skiing. And I think this is an analogy that I'm definitely stealing from another place that I read it and found very insightful. But let's say you 

[00:26:23] RS: I think it was Robin Carhart Harris. 

[00:26:25] SL: Oh, is it? Yeah, we'll just put that in perspective and then we can bring it back to that analogy. But just having, a down hill skier is gonna start forming tracks. And then the more that they go down the track, the harder it is for them to veer off track.

[00:26:38] They can only start where they are. And then the more the more neurons fired together, the more they fired together the more they wire together. So those pathways are very set in, whereas psychedelics as it refers is like a fresh coat of snow. And now you don't have these tracks that are laid out.

[00:26:54] And then now the skier can go whichever way they want. They can have new thoughts about improved self-talk. And so with psychedelics there is , there is a disintegration or a dampening of the default mode network, which is often associated with depression. And the default mold networks are the regions in the brain that are active.

[00:27:12] When you're just not particularly focusing on the task. A lot of times when you're daydreaming, also when you're ruminating. And so there's been decreased and there's also been, research that shows a de decrease in the default mode network is also associated with meditation.

[00:27:25] And then it can also alter these brain connectivity, so with different regions. And that's a big form of neuro neuroplasticity. And then in terms of research we've, I've seen, one study where it was looking at I think doi which is a serotonin receptor agonist synthesized by Alexander.

[00:27:42] And has similar effects as compared to lsd, think have said. And they've given. D i this psychedelic compound to I think mice and then saw gene expression changes as well as histo modifications what you were talking about before just how tightly the DNA around the proteins contribute to determine how what, how much gene expression can happen.

[00:28:09] So they've seen history modifications, which is an epigenic marker with d o i and mice. And then they've also, I think one of the first studies in Epigenics pretty recently was looking at ayahuasca and people who have drank ayahuasca taking their saliva samples. And then you can look at epigenic markers in the saliva samples and then have seen changes in DNA n methylation on, I think they just looked at three genes that are associated with stress induced psychopathology genes that are also associated with HPA access.

[00:28:38] And then they've seen changes in DNA methylation levels from, drinking I Alaska. So those are very interesting findings and I think, the convergence of epigenetics and and psychedelics is inevitable, but it's very new. 

[00:28:52] RS: Yeah, I it's fascinating. I feel like humanity has forever been debating nature versus nurture, right? This is just another crazy sort of layer on top of that. But now we actually have the tools and we have these ancient medicines and these two coming together, and now we can actually form some correlations. The secret is, of course, we have to wait to see is ultimately how much do we attribute to correlation and imposition of science? like I feel like sometimes we get in the realm of phenotyping really hard about something we actually don't know. There's simple correlation, but it's not actually direct causation. You know what I mean? 

[00:29:24] Coming to the commercial realm and the work you're doing at Porta Sophia now... you have this background in science and molecular biology, epigenetics and looking at the connection between stressors and psychotic disorders. But now you actually come to the realm of commercial science, which is really the realm of patents and then applied to psychedelics, which is again, super timely, particularly in the last year. I think we are in much better place to have a mature conversation about what is patentable, what should be patents, or even to ask what the hell are patents, and why do patents even exist?

[00:29:56] So before we get into that philosophical space, tell us a little bit about what Porta Sophia does. Why does it exist? 

[00:30:04] SL: So Porta Sophia is a nonprofit, it's an online psychedelic prior art library, and it's free for everyone to use as a resource. And so Porta Sophia came about, I think in early 2021 and really in response to what was happening in the psychedelic landscape, especially around intellectual property.

[00:30:22] So we know that, in the last decade there's been a huge resurgence in mainstream interest in psychedelics and cause. That there's, a lot of commercial interests, like you said, a lot of universities are doing research. The media is covering it more and more in the last decade.

[00:30:37] And because of that, there's also been an increase in intellectual properties. So specifically in this case, just patent. And and so a patent just to give a little background is a government granted, government issued right to monopolize an invention and to exclude others from making, using or selling the site invention for a limited period of time.

[00:30:58] And so that's a patent. And the whole, the point of patent actually dates back to the fourteen hundreds in Europe and it was actually meant to stimulate innovation by allowing inventors to disclose their new technology into the public domain so that, everyone else can be aware of it, but still allowing them those exclusive rights to benefit from these inventions.

[00:31:19] So as a public good to, push on public knowledge forward and incentivize pa people to invent things. And so that was original idea. So a patent should only be issued if it is novel. It is non-obvious. So novel meaning that there's never been anything done like that before, that is, has been recorded. And then non-obvious, meaning someone of ordinary skill in that field. Would not find the invention like an obvious thing. And then it's also, it should be useful.

[00:31:48] And so those are the basic requirements and also you cannot patent invention twice. And so those are the basic fundamental requirements. For a good patent at least. That was that was what the intent is in the patent space. And that works very well in other fields. But psychedelics because of the unique history of psychedelics it's been around for thousands of years in indigenous communities.

[00:32:10] And is being practiced there and then, But it has it really came to the western world in like the fifties, sixties, and maybe early seventies. But there was also the prohibition and everything was outlawed. And so there's a really big gap. A lot of that research went underground in places that are hard to find for the legal system or the people working in the legal system.

[00:32:30] And so it's really not in this last decade or so when mainstream academic research has picked up or any companies even went near it. And so because of this gap and, psychedelics being illegal for so long, there's there's a really big gap in knowledge of. People who are the patent examiner.

[00:32:46] So these are the lawyers working, let's say in the US for the United States Patent Trademark Office to decide if patent should be issued. So they're judging the novelty, the non-obviousness. They determine if this patent application is new and should be granted. 

[00:33:00] There's a lack of, convergence of the knowledge of people who are patent examiners and also a breadth of knowledge and psychedelics because of the history. Because of that, there's been a lot of patent applications that are claiming... so the claims basically outlines legal rights the specifics of the legal rights.

[00:33:18] So they're claiming things that are already in the public domain that has already been used or is documented elsewhere. And so these are not novel things, but they're not in places that an examiner would be able to find. And also, this is something that people probably don't know, but at least in the US an examiner usually only gets about 19 hours to go through a patent in its entirety from seeing it to deciding if it should be granted. And some of the senior ones only take 12 hours. So they're always gonna go to their own patent databases first. And there's not a lot of historical patents on psychedelics that they could just pull up.

[00:33:54] Whereas in other fields other molecular genetics, other technologies it's easy to find that prior art. And any of these information, available public information is called prior art. And that's why we Porta Sophia as a prior art library we hand manually go in and curate these prior art references. And that's from journal articles, old patents. We look at blogs, websites, books. Play archival research. So we look at all of these sources to to make it really easily digestible for the examiners to use us and also applicants.

[00:34:29] RS: Okay. So let me bring this all together in what I heard and what I understand. For a patent to be genuine, and I think patents are a good thing because they incentivize innovation. Now the question is what is a good patent rather than whether patents are good or not.

[00:34:44] A good patent means that something is genuinely novel. By novel I mean it, something that is, does not exist in the public domain, is not prior art, essentially. Meaning that there's no preexisting knowledge that somebody with ordinary skills, and I'm, in quotation marks, ordinary skills, would not be able to replicate that.

[00:35:03] So that preserves the expertise that someone may develop over their life or through training and stuff like that, that they won't be able to develop. And then that invention, that generally novel invention, has a particular use that is also novel. Now, where the trouble comes is that, like you said, that we had almost 50 years of prohibition where the research went under the ground or simply disappeared.

[00:35:29] There's a huge gap in knowledge. Now where things get interesting and political and all science, I believe, is political ultimately because it is subject to the access, the infrastructure and the awareness of people. Whenever people are involved, it's going to be political. So you have, let's say, somebody applying for a patent and making these claims, genuine or not, they're making claims.

[00:35:51] Somebody at the patent office, like you said, a lawyer who will then spend on average 19 hours, to your point, determining the validity of that claim. Now for areas of knowledge where there's a large prior art and a public library and a public domain that is rich with knowledge, that might be easy. For areas of psychedelic science, which has been stigmatized or criminalized, that has basically disappeared for 50 years, a patent officer may go oh, this is genuine because I can't find anything that exists before this, which might be completely wrong because that research despite existing is not easily accessible. And if it takes 50 hours versus 19, somebody be like, oh yeah, I can't find anything on Google. Okay, damn patent approved. There you go. Make money for 10 years. That's really what's happening, right? fascinating. I find it so fascinating. So your Porta Sophia is essentially protecting the public domain by making what does exist in the in prior art and the public domain, making it more obvious and accessible to patent officers. Is that right? 

[00:36:55] SL: Absolutely. That's the goal. Porta Sophia we wanna support good patents, stimulate innovation, and assure that these medicines can be accessible at scae for people who need them. All of the things that we're doing is to support of the that mission of ours.

[00:37:09] And then in terms of making prior art accessible, so we build this library and that's for anyone to use patent examiners, as well as inventors, as well as just general public who's interested in, in, in prior art and psychedelic literature. We have two prong to our strategy and the other strategy are our third party pre issuance submission efforts.

[00:37:29] And I think this is something that you'd be really interested in. So this is a way working within the legal system in the US and in other countries. In the US where we can, as a third party submit prior directly to the examiner in. In the process of their examination. So we can actually in our prior art search, so patents are published on a weekly basis patent applications.

[00:37:51] And then every week we go in and look at the newly published applications. And then we track. We have 33 compounds that we're tracking, psychedelic compounds. We've finished 12 of them, comprehensive search of all the patents regarding those. And then so we evaluate these patent applications and sort them into three tiers.

[00:38:08] And then tier one is the most we would say overly broad patents. So those those are the the claims that are claiming existing knowledge those are like overly broad without data in the application to support the scope of the claims. There could be threat to the field if these are granted.

[00:38:25] And also we look at applicants, so are they filing multiple overly applications? And so for the ones that we deem to be overly broad we file third party submissions on the select few of those. And so with these, it's basically compiling a chart where it's like the verbatim claims on the left and then the evidence the excerpts of evidence on the right.

[00:38:45] So it makes it really easy for patent examiners to when they receive this and they're obligated to account this in their examination process. And also the applicants receive notification that somebody has filed a third party submission on them, their application. And this makes it really easy for examiners cause they basically get sent this evidence and then they can use that to determine if the claims need to be narrowed, if they're just rejected.

[00:39:09] And we have filed 12 third party submissions and also observations internationally in different countries. And we've seen some really incredible impact already in the first three. That was file starting February applicants have actually amended their claims and narrowed them in scope.

[00:39:25] They've taken out the overly broad claims replace them with more just specific compounds that they're focused on. And then we actually had a recent one where was an application claiming using psilocybin and other psychedelics to treat headaches which have had, extensive research.

[00:39:39] And so we provided the third party submission. And the USPTO actually just announced that they had a non final rejection of this application. They had actually said, based on the prior art submitted during the third party submission that we filed. So it's really great to actually see impact that we're making in this space with both the library and these third party submissions.

[00:40:02] RS: That's really interesting, because usually what would happen is that some entity would file a very broad claim , and then of course another party can dispute that claim through an appeals process, but it's very very time consuming resources and money. What you're doing is you're preempting that appeal process by filing a claim and saying that, just so you know, FYI, , this already exists, so if anybody attempts it in the future, just so you know, this already exists.

[00:40:30] That's essentially what you're doing. 

[00:40:31] SL: Exactly. And so we actually have one of our colleagues present at Horizons just describing our process and our progress. And so on average it takes us about let's say 40 to over a 100 hours to file one of these. So they're very lengthy, like work.

[00:40:47] But but when it comes to what you're talking about like challenging a patent after its issue d like the Post grant review process that could be sometimes in the millions of dollars with a lot of costly time commitment and often takes possibly over a thousand hours of legal experts time.

[00:41:05] So Porta Sophia's intervention really is in the front end. So the prior art stage, before patents issue to provide that information to the examiners, at the early stage. So we don't have to waste a lot of money on patent litigations. And 

[00:41:20] RS: I wonder whether Porta Sophia, if it wasn't for psychedelics, something like Porta Sophia should would ever exist. Cuz you wouldn't need to. Cause you have a really rich ecosystem of knowledge already. You exist by virtue of prohibition that happened. Now there's this huge gap in the cultural consciousness about awareness about what these psychedelics are.

[00:41:39] SL: I can't say for sure, but I would guess so because these patent examiners are incredibly skilled lawyers who are experts in their field. And it is like a very common strategy in patenting to go as broad as you can initially. It's the stands of patent examiner restricts and then you amend the claims and then you figure out the set that works up.

[00:41:59] You can claim the most things without overstepping. But then that doesn't really work with this field cause of that gap. So that's why Porta Sophia was created and we're here. 

[00:42:08] RS: Interesting. Okay. And one last question and then we're gonna switch gears. You said that you are focused on 33 molecules in particular, what determines that number?

[00:42:18] SL: So these are the most common molecules. Things like psilocybin, lsd, MDMA, those are all up at the very front. And then as we get more into obscure ones, so this is just a short list that we're continuing to add every time we get feedback from the community or we're seeing trends that are currently in applications that come out we add more to this list. So 33 is like our comprehensive prior art, our our comprehensive patent search that we use. But a lot of these patents cover, 50 different compounds. And so those are all in our database as well. Oftentimes overly brought patents will claim multiple compounds, not just the one that they're focusing.

[00:42:56] So those are all in our database for future references. And when we look, when we add prior art to our library, which we do add on a weekly basis we that prior art is directly from the patent themes that we're seeing in the latest applications that are mostly tier one through three, starting with tier one.

[00:43:13] It's not a comprehensive library, but it is a library enriched in patent related themes, which is what we're mainly After. 

[00:43:23] RS: Of course. And you, ultimately the goal is to make the whole ecosystem better, right? . So you have to start somewhere and prioritize what are the most commercially valuable, compounds. Amazing. I feel like I could talk about this sectional alone forever. But we do have other really important things to discuss. So I'm gonna switch gear, take a hard right... I think it's important to come down to the personal level, right?

[00:43:43] Because ultimately that's the source of conviction for, people like you, people like me. Why do we do the work that we do? What was your most meaningful psychedelic experience? Why was it meaningful? Please feel free to share whatever you feel is appropriate to share on a podcast

[00:44:01] SL: yeah, this is a great question. And to be honest, I have thought a lot about what I wanna share and I will say that I have had one significant psychedelic experience. I won't go into the details of what compound or one or with who.

[00:44:14] And that is really because, I am in the psychedelic space. I'm working in this space. But these powerful compounds are still illegal in the US , I think we have to remember that. . And there is from my upbringing, follow the rules.

[00:44:26] There is like definitely still real fear about even talking about these. And there is stigma and that's also one of the reasons why it's so important to talk about it, to destigmatize them for, people of my, my culture as well. Who really could benefit from these very powerful medicine.

[00:44:44] And so for, from my experience, it was a couple of years after graduate school and I had really experienced some, deep depression, a few bouts of just severe depression almost debilitating as well as anxiety. In during graduate school, I had panic attacks where it was so bad that I I would, lose my vision.

[00:45:04] I would see purple. I would feel tingling in my arm, like shortness of breath and then tightness of chest. And basically not be able to, continue to function. And I remember, driving from campus to other parts of the building for research and then just having, carrying my sample, but then feeling like an anxiety attack, panic attack, come on, and then having to pull over on the side of the road to write it out.

[00:45:27] So this was like pretty severe, anxiety and depression. And I had really spent a lot of time, I was doing everything I can to try to heal myself. I was seeing, psychiatrist, I was on ss, I tried multiple combinations different drugs. I was exercising, meditating, all of the things you could name.

[00:45:46] And it just was not helping with the depression, anxiety, it was really in a very desperate place. And eventually the SSRIs like worked, but then there was terrible side effects. And then after graduate school I had come off of them and then, but was like, Still feeling, the low key depression not debilitating, but still feeling it.

[00:46:06] And then I had, learned about psychedelics and just the incredible potential for therapeutic potential of these. And then so I tried them and it really I just cried for the first two hours. I just I just felt, I just cried so much. And then just purged all of the sadness and the fear that I was having.

[00:46:25] And then after the crying session, it was really just like a deep sense of safety, which like, I honestly before that moment, could not recall the last time that. Felt that safe, maybe even since childhood. Just a deep sense of safety and a deep sense of like belonging and love and that I was, not alone.

[00:46:46] And and I think like the, for me, really the takeaway was that like, like when you're in, depression or in fear like understanding the concept of safety, that you are, technically pretty safe versus feeling a sense of safety is very different. It's like description of a taste versus actually tasting it.

[00:47:06] It's very different and it's just, for a very long time I hadn't felt safe and I was like thinking, reflecting on that, just, I feel like psychedelics could have such tremendous potential with like racial trauma and, trauma from immigration. Just feeling that sense of safety potentially for the first time.

[00:47:27] To be completely like safe is just I think that could have huge potentials. Yeah and it's something that, I had just and the side effects of SSRIs are just awful. And it only works for select few select population and the effects decrease with time. So I think, and it just reaffirmed my sense of community, like my sense of belonging to myself, to my own authenticity and history and background and culture.

[00:47:53] It just, it's it just felt, I felt safe and I didn't feel shame. It was really transformative. 

[00:47:59] RS: Beautiful. Thank you so much for sharing. This is perhaps a loaded question, but I'm curious how, knowing what you know now, the work that you do, everything that you shared about epigenetics, but also upbringing... you talked about feeling a profound sense of safety and belonging for the first time. what do you attribute to not feeling that way prior to psychedelics? 

[00:48:23] SL: Yeah, I think I think when it comes to safety, just like the sense that you, the way that you are is alright is a huge part of that.

[00:48:33] And then I think, because of, my immigrant experience and also being. oftentimes the only minority in the room, it feels like it feels like I ha like I have to be a certain way in order to feel safe. And I, that's almost so integrated. And I think psychedelics really just brought up the idea of that I can just be like, I can be who I am, and that's okay. that's especially I mean leading to, the pandemic covid 19, especially in 20 20 with the increase in hate crimes against Asians and Asian Americans. And really, during the early phase of the pandemic was when I had experienced very covert danger and from racism for the first time. There's been, very covert racism throughout, know, growing up in, in the two thousands, nineties. But this sense of I could be, I'm just walking down the street, walking my dog, but then I have, a Chinese face and also at the time hearing like political narratives of the Chi China virus and go back to your country, these kinda things where it's like I would be walking in the street and then this was like the fight between the mask mandate as well, and It's like very common in Asian cultures to wear masks, to protect yourself when you're sick like for other people to not be contagious.

[00:49:48] And like I had never really thought about walking down the street with my face and also wearing a mask, being a political statement and the political risk. And then also like just, talking to my mom and she lives by herself in Chicago and she goes to Chinatown to get groceries because there are, Chinese vegetables that are only available in Chinese grocery stores.

[00:50:08] And then just thinking talking to her, I remember during the peak of those, the fears and then just her describing that Chinatown is like desolate and there's, no one around and there's really like tension when you're there grocery shopping that everybody's on edge and you can just feel it.

[00:50:23] And that Fear and sense for safety that there could be a shooting or there could be like, violence is really terrifying. And, I worry for my mom. And it's also like Chinatown is usually a tourist place where there's like bustling and everyone's eating at restaurants, there's people taking pictures.

[00:50:38] So that was like very dramatic shift for me in terms of the sense of safety. And I also recognize that it is very privilege of me to really have only recognized that, the sense of safety walking down the street with my face. As a Chinese person, I know people, African-Americans, people have other races, have experienced this their entire life.

[00:50:58] It's not just because of a pandemic. And so just I think a lot of this awareness and, for the first time it really dawned on me during this critical time. 

[00:51:09] RS: We talk about personal liberation in one way with psychedelics, but I think to understand where you fit in the larger picture is also equally liberating, right? Because again, going back to the idea of duty and responsibility gives you a sense of, okay, this is where I am, this is how I fit in with everything else. This is how I am in the general ecosystem. And from that, like now that I'm free, what do I do? What can I do? What should I do? I think that's really important. 

[00:51:37] So I wanna bring us to the last part of the conversation. You're doing a lot of work particularly with building coalitions and alliances of people with similar lived experiences. going off what you just mentioned, your experience with psychedelics and also seeing what was happening in your community, the Chinese American community, particularly in the pandemic, why is work like this important and why is it important to build alliances of people with similar lived experiences? 

[00:52:06] SL: I think it's really important to build community. Having a sense of community and just humans supporting each other is build evolutionary in our genes.

[00:52:15] Living a good life is to have that connection with other people and the larger world around us. And so with women in about health so this is a mostly Wisconsin located group. And I've been in this network for five years and it's really creating, networking opportunity, career advice, like just connection among women in the Bell health industry.

[00:52:35] And and so this last year I co-founded this mentorship program, and mentorship has been so important to me too. I feel like I have really soughted out and have received great mentorship throughout my career and my personal life that has led me to, to the the things that I've been able to experience today.

[00:52:53] And I've had a really great mentors that have helped me with career advice and I wanted to be able to bring that to my community. I've experienced a what is a first round mentorship program a couple years ago. And I just just loved my mentor. She was incredibly helpful and she actually wrote a recommendation for me for one of an application that I honestly read her recommendation letter when I feel down about myself to pick me up.

[00:53:17] So I think it's so important for mentorship and supporting each other, making that connection. Created the mentorship program last year. That was the pilot program and that was just really great and successful. We made really great connections especially in Covid. I think there is really a lack of feeling connected to other people that I think this program helps offer.

[00:53:34] And we're actually in the middle of of ramping out for the second round of women in mentorship women about health mentorship program and with the Asian psychedelic Coalition. This is a pretty new effort. And Simran reached out to me. She is the lead for this this effort and we just connected, coming from different backgrounds and I think, the Asian Americans, Asian Canadians, the Asian diaspora, there's so much diversity within what is asian. So we've come together a group of people with such diverse backgrounds and in this field wanting to connect more to just live meaningfully to bring, more activism, awareness, education, more resources. And it is something where I think there is, a need in the psychedelic space.

[00:54:18] Like a lot of, academic research is mostly Caucasian subjects. That's a big problem in this field. Like someone like my mom who has struggled from depression. There are really no, Mandarin speaking psychedelics therapist. Let alone it's hard to find a Mandarin speaking like psychiatrist, even in city as diverse as Chicago. She would not be able to receive these these therapeutics because of the lack of diversity. I feel like I'm in a position that could make a difference now and use my voice to be able to advocate for people to, to destigmatize. And building community is a big part of that. And I think a big part of the effects of psychedelics is feeling connectedness with other people, open-mindedness. And I think part of just living a good life is also connectedness. 

[00:55:02] RS: What a beautiful way to bring it together. You talked about stress inoculations, and here we are talking about community, right? That's perhaps the most important aspect of building resilience and building a sense of belonging. Sisi, this is fantastic conversation. Thank you so much for spending the time with me and hanging out with us today. 

[00:55:20] SL: Thank you so much. Thanks so much for highlighting the voices of, the Less heard that is really important work.