The Bioinformatics CRO Podcast

Episode 53 with Linnea Fletcher

Linnea Fletcher, Biotechnology Department chair at Austin Community College and Director of the InnovATEBIO National Biotechnology Education Center, discusses training technicians to tackle real world challenges in the biotechnology industry. 

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

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Linnea Fletcher

Linnea Fletcher is Biotechnology Department chair at Austin Community College and Director of the InnovATEBIO National Biotechnology Education Center.

Transcript of Episode 53: Linnea Fletcher

Disclaimer: Transcripts may contain errors.

Grant Belgard: [00:00:00] Welcome to The Bioinformatics CRO Podcast. I’m Grant Belgard and joining me today is Linnea Fletcher. Linnea, welcome.

Linnea Fletcher: [00:00:07] Thank you. And thank you for having me on your podcast.

Grant Belgard: [00:00:11] Thanks so much. Can you tell us about what you’re doing at InnovATEBIO and at Austin Community College?

Linnea Fletcher: [00:00:18] Sure. So I’m the executive director for InnovATEBIO, the National Biotechnology Center Grant, and it’s funded by NSF, the National Science Foundation. And my job as being PI on this Grant is to support and coordinate bio technician training across the nation. And there’s over 130 programs. But this also means I have to know about the career path starting from K-12 all the way up through PhD, because most of my students and the students across the country who become technicians continue their education. To keep boots on the ground, so to speak, I still run a program at Austin Community College where I’m educating individuals to be technicians. And just to give you a snapshot of my students, I have a high school program. It’s fairly large, and these students get a certificate in bio manufacturing. Most of them go on to four year schools. Some of them come into my two year program, and my two year program has both two year students who tend to be older adults coming back for another career. And the rest of them, 50% of them already have a four year degree. And I’ve been in the area long enough that local industry tells the four year student to come and get an advanced technical certificate from that community college down the street because I’m the one who does. I emphasize hands on training. Some people have said it’s like graduate school in a regulated environment on steroids because they learn a lot in a space of a year, the four year students.

Grant Belgard: [00:02:07] How common are programs like that elsewhere in the country?

Linnea Fletcher: [00:02:11] Well, actually 130 programs is not a huge number across the nation. And I would say they cluster around the biotechnology industry clusters. For example, here’s a lot more in California and also there’s some in Florida where you are. And I work with them because Florida actually is a great job of training the workforce. And there’s more in North Carolina. And of course, there’s a large number in the Northeast. So it really depends on how much industry is present for these programs because they are workforce programs. So you have to justify your existence by having companies in the area that need your students.

Grant Belgard: [00:02:56] How do you get that feedback from local companies?

Linnea Fletcher: [00:02:59] Well, an advisory board, all these programs have an industry advisory board and I meet with mine once a year to get feedback on what I’m teaching. But then also, like many other programs, community colleges don’t have a lot of full time faculty. So all of my courses pretty much are taught by adjuncts and they’re all from industry. So they tell me what I need to put in my program constantly. And as a result, there are a lot of basic biotech people need to know that doesn’t change, like how to make a solution or the math or the regulatory affairs because we have QA QC and we do run our program like a company, so they have to do all the documentation. But all the emerging technologies, we had to modularize all of our curriculum such that when we needed to change out a module to put in a new module based on an emerging technology like we just added metagenomics and we took out another module that was probably a little out of date to add metagenomics and the ability to do next gen sequencing, which is so important.

Grant Belgard: [00:04:18] Do you find a large degree of variation metro area to metro area in terms of the skill sets that are needed? Or are they mostly shared?

Linnea Fletcher: [00:04:31] Well, it’s kind of interesting. Local area dictates needs, but usually local area mirrors what’s going on across the nation in general. Some of the bigger differences are if like North Carolina, California, where’s the large scale biomanufacturing that is going to be different than the small scale biomanufacturing or mid scale that teach because I’m not doing reactors that are doing like 200l. I’m doing much smaller reactors, so there are variations. I also have a lot of medical diagnostic companies and so I do a lot of PCR and real time qPCR because my students need to be able to do that kind of technology in the companies. We also have a lot of maybe more instrumentation, HPLC, GC, maybe some mass spec. One thing I am looking at incorporating is flow cytometry, which I haven’t done yet, and we do stem cell too. So you’re right. I can tell you all the different areas across the country, like in Wake Forest, also in North Carolina, there’s a lot more regenerative medicine. And then in the state of Washington, they have a lot of immunotherapy.

Grant Belgard: [00:05:57] What changes have you seen over time in the skill sets in short supply?

Linnea Fletcher: [00:06:03] So what I’ve seen, I’ve been in training individuals, educating them for 25 years. And I would say that it has become more complex in terms of what technicians need to know as essentially the industry is converging more with other areas. So as biotech advances into other areas overlapping, such as nanotechnology, electronics especially, you see this in medical devices, in regenerative medicine, and then the need for another one that I’m now having to anticipate is AI, artificial intelligence and robotics. So now my students are actually having to learn how to program machines to deal with cell sorting and identification and running some of the automation in terms of the equipment in laboratories.

Grant Belgard: [00:07:10] What areas would you say have the most unmet demand right now?

Linnea Fletcher: [00:07:15] Oh, unmet. Well, definitely in regenerative medicine and immunotherapy and a new set of skills standards have just been published by the Wake Forest Institute for Regenerative Medicine. It was a grant funded activity in this area of what technicians need to know be able to do their jobs. If you think about it, in many cases they actually have to take care of the cells that are removed from patients and grow them up before they’re genetically modified and put back into the patient. So that is a major area that’s not being covered. Large scale biomanufacturing, we’re not meeting the demands for the technicians in this area. And so that’s something that has to be addressed. And then another area that hasn’t even quietly shown up on our radars is Bioindustrial. And I’m already working with process technology programs. And if you process technology, is the oil and gas and chemical industry because Bioindustrial is large scale chemical engineering and the idea of having those programs actually educate students to cross over from oil and gas into Bioindustrial is something that we’re working on for the future.

Grant Belgard: [00:08:45] That’s interesting. Certainly I think at the level of PhD training, you have some quite a bit of segregation among students who would be doing immunotherapy versus those on bio applications in oil and gas. But I guess at the technician level, you have options in essentially the same program where you’d be sending students to those very diverse industries afterwards.

Linnea Fletcher: [00:09:12] Yeah. And that’s what kind of is interesting is so when someone gets a PhD, they usually it’s in one area of research and it’s very targeted and they have to do that, become experts in a narrow range where my technicians and the technicians that are being educated across the country, they learn a variety of skills from cell culture, manufacturing, bioinformatics, instrumentation, such that they can go into a variety of different jobs within the industry. It’s like very similar to what is now happened in MDs, focus on one area. But physician’s assistants, they actually get education in all different areas and they actually can move from one area to another area that’s just like my technicians. And they do it based on changing interests.

Grant Belgard: [00:10:14] And what changes do you see that might be coming down the pike for the workforce?

Linnea Fletcher: [00:10:19] Well, for one thing is we need to do a better job within the governmental sector to make sure that there is a promotion of educational institutions working together instead of working in silos. For so example is if someone is in K-12 high school programs in biotech, their courses need to transfer to a variety of institutions and get credit, two year and four year like advanced placement and then biotech programs, their courses near to transfer to four year schools. And I know it’s hard because they don’t necessarily have the same courses. But the thing is, if you don’t do that, students don’t want to be in biotech, if not all their coursework transfers. And the other trend that needs to be worked on is if someone in industry learns what’s equivalent to one of my modules, they need to be able to test out of that module or a course in my program and get credit for what they’ve learned on the job and not have to repeat any of that training or education. It’s a waste of funding and money and time. So essentially how anyone learns, whether it be on in industry or in an educational program, they need to be made equivalent and we need to work towards that if we’re going to meet the needs of the workforce. Workforce needs are going to increase, not decrease, as biotech becomes more important across the board in all these different industries. It’s now even applicable for solutions in climate change. It will make manufacturing sustainable.

Grant Belgard: [00:12:22] That’s a great point. I really like how your program has this advisory council and it sounds like you’re very nimble and adaptable to what those needs are. I can say from our perspective in terms of what we see, which we’re looking at a very different workforce. We’re typically looking at PhDs in bioinformatics and related areas. There is often a mismatch between what is needed, like the skill sets needed in the biotech industry from the skill sets that are frequently trained in PhD programs. I mean, they’re broadly congruent for sure, but there are definitely some areas where there is an excess of people with those skills that just aren’t aren’t needed that much in other areas where there’s a glaring deficit. And my sense is in PhD programs, the skill sets are driven by the research programs of the PIs in the department. There’s not this close tie or not as close to tie to industry groups as your program has. I think that’s really interesting. And I wonder have you seen much of a movement to try to take those industry needs more into account in PhD training as well?

Linnea Fletcher: [00:13:44] Well, it’s interesting you say that. I have seen that. Of course, what I’ve always seen is if you look at engineering programs, engineering programs traditionally have close ties with industry and they run their labs more like what’s going to occur in industry. In fact, if you look at engineering programs, you’ll see that a lot of their funding comes from industry and they’re educating people mainly to get into industry and not necessarily into research labs. The one thing I thought was really good, I can understand why PhD programs like in Biology or some of the more pure research labs aren’t tied to industry because you do need pre-research, that research that isn’t always necessarily applied because industry research is applied research. But I felt that after getting my PhD and getting involved with educating people for industry, the QA QC that I learned and now I’m teaching my students. The regulatory affairs information and the need for documentation was actually a great way to run a lab and ensure quality within the laboratory. So I feel that even if you’re doing pure research that isn’t applied, taking some of the quality assurance and quality control principles, total quality management and applying it to some of the PhD programs would not be a bad thing. You’d end up with students that are better able to run their own labs once they finish their PhD and do a postdoc.

Grant Belgard: [00:15:40] That’s a great point. It’s so common for people to have trouble tracing exactly what solution was used in a particular experiment and so on and so forth. These things come up in academic labs all the time where the documentation is not to the standard of industry and it causes problems. Other things that you think doctoral training programs could take from this?

Linnea Fletcher: [00:16:07] Oh, I do think one thing I think is really worthwhile is so I was an unusual PhD student in that I did two different postdocs, two different areas. I always felt that that was beneficial, because then I actually had some education in other areas that could be applicable. And I feel at this point there’s going to be more convergence of science areas. And if you’ve had experience in different areas and you encourage that, you’re going to be better able to take advantage of opportunities from other areas in science. So my first postdoc was in immunology on monoclonal antibodies and my second postdoc was on the 3D structure of messenger RNA. Totally different areas, but it has served me well by doing those totally different areas. I’ll tell you, my second postdoc, I had a luckily the other postdocs were very patient with educating me with the molecular biology techniques that I needed to know because I pretty much was a straight biochemist. And then of course, the immunology I had to learn and the monoclonal antibodies. So each time I’ve put myself in a place that was slightly very uncomfortable, but I gained a lot by doing that.

Grant Belgard: [00:17:42] What do you think are the lessons PhD programs can take from that? Would that come at the point of rotations? Not all schools have rotations before students select their labs. So I did my PhD at Oxford, for example. We didn’t do rotation. I think rotations into a lab and finish your degree in that lab.

Linnea Fletcher: [00:18:01] Yeah. I think actually rotations before you make your final choice should be obligatory.

Grant Belgard: [00:18:08] And do you think doing it over the course of a year is adequate or do you think maybe that it would be beneficial for that to be prolonged?

Linnea Fletcher: [00:18:17] Well, I think you’re only going to get everyone to agree to a year.

Grant Belgard: [00:18:21] Yeah.

Linnea Fletcher: [00:18:22] To be honest.

Grant Belgard: [00:18:23] [] what’s possible?

Linnea Fletcher: [00:18:24] No, I think a year would be enough. Right, exactly. Because I totally understand what my husband, he’s also a PhD in microbiology and he ran a lab. I totally understand why he has to have his group focused on the work that he’s doing. It’s so competitive.

Grant Belgard: [00:18:44] And changing gears a little because I guess this is starting to affect everything. How has ChatGPT and the explosion of other AI tools on the scene in a very powerful way in recent months impacted, how you’re doing things and how do you anticipate that will impact the training you provide going forward?

Linnea Fletcher: [00:19:09] So I actually was part of a project that I had to develop an AI module for biotechnology programs, and the other faculty members at the community college had to do it in their area like computer science. The main thing I saw is that just like any new technology, you need to quickly understand what are the limitations and the advantages, especially the limitations. And I think it’s really interesting. I now have students when they have to write up original work, I have them write up their original work and then I have them put it in ChatGPT to show them what it would look like. And if you ever do this with students, the other thing that’s really interesting if you have them use those, the AI write up an original article, what’s supposed to be original article based on what, they should understand how it gains the information then ask it to do references. All the references will be false. So the main thing is they have to understand the limitations. And now it’s being used in medical diagnostics. Well, it’s only as good as whoever programmed it and what’s available. And that little hint of innovation and original thought that very much is a human trait may not be there. So you have to keep that in mind when you use these. They’re only as good as who programmed it and gave it the information. It’s only as good as the databases it has access to and is researching to be able to do what it’s supposed to do.

Grant Belgard: [00:20:57] And given the rapid increase in what these tools have been able to do over even the last 18 months, what are your thoughts on on where that’s headed? I mean if you look out five years from now. I mean, this will certainly be a lot more powerful than they are now. And no one knows how much more. But how would you expect that to shape the workforce?

Linnea Fletcher: [00:21:19] Well, I don’t think it will decrease the number of jobs or anything like that. What it will do is require that my technicians or the technicians across the country being educated will actually have to know how to use it effectively and be able to troubleshoot it. And then once again, it’s adding another area for technicians, depending what they’re involved in, to have to learn. And that’s the other reason why I think we really have to tie our educational institutions together, because students can only, they’ll gain so many competence passes through high school, so many competencies through two year and then four year and on up. It scaffolds the information. And we all have to do a better job of making sure that we interface better with this instead of having no overt. We don’t need overlap, that’s for sure. We’re going to have to do a better job. And one thing I focus on that I think all educational programs is that my students know exactly what are the outcomes for their education, and they can articulate this in an interview. And when they don’t know something, they’re very honest about it and they know what they don’t know, but how to get the information. You can only teach somebody so much, but they have to know what they don’t know. So and be able to articulate it and not promise anything.

Grant Belgard: [00:22:56] Do you have any training for job interviews and.

Linnea Fletcher: [00:23:01] Oh, yes. We do from the very first course on. We have like seven courses. So the very first course is career awareness, because I can’t afford them to get to internship and not know what area of the industry they want to be in. I can’t afford to have them get into an internship and say, Oh no, I didn’t want to do this because it takes a lot of time for companies to do internships, so they have to review everything that’s local. Every semester they change their resume based on what they learn in the program. They have to verbally articulate that to the instructor every semester. And then the the Gate is an interview committee when they are doing their internship. We’ve learned the hard way. Oh, the other thing is the class size for my program is 12, not 24, not 200. So that’s why it’s like graduate school, because every student has to demonstrate in the lab they can do it by themselves and not in a team, even though we have them work in a team so they have no chance of getting someone else to do it for them. And they do a lot of presentations.

Grant Belgard: [00:24:28] That’s great. So there’s a book I always recommend to people entering this space by Toby Freedman called Career Opportunities in Biotechnology and Drug Development.

Linnea Fletcher: [00:24:37] Yes.

Grant Belgard: [00:24:38] Are there any books that you would advise for listeners who might be just getting into this space?

Linnea Fletcher: [00:24:44] Well, if anyone wants to educate people, Lisa Seidman for Madison College has like the Bible in how to educate people for this industry and also for the students. It’s by Tech Manual by Lisa Seidman and then other books by Freedman. I’ve read all his books. He has several books that I think are worthwhile.

Grant Belgard: [00:25:09] It’s fantastic. What advice would you have for the listeners of our podcast? many of them are people who are in bioinformatics or they’re interested in bioinformatics, and some may be considering going to biotech for the first time, having only worked in academia. What advice would you have for them?

Linnea Fletcher: [00:25:31] Well, one thing is everyone should keep up on emerging technologies and there are a variety of sources in addition like your podcast and then other areas. You need to always keep aware of where the industry is going and what are some of, I read science religiously nature. I have to admit, I do a lot of reading and listening to podcasts and then the other thing is you have to really consider the fact that whatever you pick for a career, most likely you won’t stay in. So always be open to opportunity. Most people nowadays don’t stay very long in one job. They’re constantly looking, not necessarily because they’re dissatisfied with the job, but their interests have changed. Or they want to try something new. And I say you should always be willing to do that. So keep an open mind. My husband as a microbiologist, he went from the university to the chemical industry and he ended up in the petroleum industry. That wasn’t planned necessarily at the start.

Grant Belgard: [00:26:46] Right. I think that’s kind of a theme from the people we’ve interviewed on this podcast. Very few people had followed a career trajectory they imagined when they were a student. There were a lot of things that were unplanned. There was a lot of serendipity. A lot of people ended up in roles that in some cases they didn’t know even existed at the time, or in some cases didn’t even exist at the time as new jobs are created and so on. How do you think academia, government and industry could work better together?

Linnea Fletcher: [00:27:24] Well, for one thing is I don’t think there’s enough funding opportunities that foster and promote collaboration among the educational entities between high school two year, two year and four year. And I think there should be more. I think if they’re not willing to do it themselves, it should be possibly forced a little bit more with opportunities that foster collaboration. I do feel we need even more input from industry. In fact, there was a paper out by ACC, the American Association for Community Colleges, that was done by Harvard, and it indicated that we need a lot more input from industry concerning these educational and training programs and for them because we need to know more what they need and be able to anticipate. I know they’re really busy, but if they want the very best employee, we need their help and their voice. I think there should be more apprenticeships and more internships and apprenticeship programs that you can get scholarships and are paid for like some of the what the other countries do because that’s the best way. At least I know for my companies with internships, they hire these people or bring them on in internships with the thought that they’re going to stay in the company. And if we could have more apprenticeships, we’d have more transition into industry and it would be more seamless. So I think funding in apprenticeships needs to increase, not decrease. It’ll be money well spent.

Grant Belgard: [00:29:11] There’s a lot to unpack there and it started out with one of the earlier things you said, I’m involved with a school that has been very active in getting articulation agreements in place with regional colleges and universities for credits to transfer. And in learning about the process, I was surprised at how everything it seems, at least where they are, is essentially bilateral. It’s a bunch of bilateral agreements. It’s not being done at the level of a system, for example.

Linnea Fletcher: [00:29:46] No, it’s not. [overlap] finding individual school. I know. Yeah, it is. You’re exactly right. It’s like I have an articulation with the University of Texas at Austin. It’s only for biochemistry and it’s not for the rest of the system. And it was really hard to get. And I understand their concerns because they’re worried about quality. How are they going to monitor the quality of the students they’re getting from my program? It’s more interesting, K-12 in a state, you can get systematic across the state if they’re called core courses and they automatically transfer to all four year schools. I think more needs to be done to figure out better ways of ensuring quality from one program to another. Now, what some states are doing is it’s called still skill standards and competency. So the students graduate from a program and it’s guaranteed what skills they can do and the state controls that. I think if we had more of this to ensure quality, maybe the four year schools would be more willing to do systemic type articulations. I get why they don’t though. We just have to work on coming up with better systems to ensure quality when a student graduates.

Grant Belgard: [00:31:12] What is your most controversial opinion on this topic? Where you’re certain that you’re correct, but a number of colleagues would disagree with you.

Linnea Fletcher: [00:31:23] You have to. Okay. So industry needs to stop requiring a four year degree in biology to be a technician. That doesn’t insure anything, to be quite honest. That does not ensure quality. It does ensure that they made it through a four year program, but it doesn’t ensure that they’re ready for the job. Otherwise I would not have 50% of my students who have a four year degree are coming to me to get an advanced technical certificate.

Grant Belgard: [00:31:55] Yeah, that was a really interesting stat you gave.

Linnea Fletcher: [00:31:59] Degrees don’t ensure quality or at least maybe they ensure quality in some areas, but they don’t ensure that they’ll be able to be what industry needs. So they need to be more focused on competency based education instead of degrees and certificates at least asked for the competencies that are associated with the degrees and say, Can you guarantee me these students can do this and this? I can guarantee industry this because we just don’t graduate them unless they have lab practicals. They test out in all of this.

Grant Belgard: [00:32:41] That makes a lot of sense. Another thing that maybe sticks out to me is not just the difference between the responsiveness of your program to what industry needs, but maybe wrongly. But at least my perception, is that there’s less of that in four year programs in the biological sciences.

Linnea Fletcher: [00:33:07] But they’re not funded to do that.

Grant Belgard: [00:33:09] Right. It seems like it’s much more about getting people ready for grad school and so on.

Linnea Fletcher: [00:33:15] So a lot of my colleagues are in four year institutions and the universities and a lot of four year, they’re not funded to educate people for technician positions, we are. They don’t even have the equipment that I have for educating students and they certainly aren’t allowed to just have 12 students in a class. And so it’s really hard to do that.

Grant Belgard: [00:33:47] You mentioned that you had a, you know, Illumina sequencer and a nanopore sequencer. And I certainly never saw these until grad school.

Linnea Fletcher: [00:33:57] Yes. The fact that we moved from the Illumina platform to nanopore and now Oxford and the fact that we put a sequencing center, it’s grant funded through the NSF at a high school, and that we actually do the same thing in our program at the two year school. So we have high school students who are doing sequencing and interpreting sequencing data as well if our students at the two year and it’s actually in the very first course of our program and the repeated again. And at this point, we’re getting the students to do sequencing projects for other departments. The biology department at Austin Community College is doing a moth barcoding project, and there’s plans to have our students do the sequencing for that project and then share the data with the biology students. So we’ll have some peer to peer sharing of information. So this way, this models what’s going on in industry.

Grant Belgard: [00:35:07] Yeah, that’s fantastic. I mean, for sure, when they get an industry, if they’re doing anything omics related, NGS is going to be a huge component of that.

Linnea Fletcher: [00:35:16] That’s how we got involved with helping start up companies, is doing industry based projects for them. And then the idea of doing undergraduate research in addition to industry based projects. I think that’s the best way to engage students because if you get them involved in real projects, especially ones that make a difference, that then they can see why they should be learning science in the first place.

Grant Belgard: [00:35:44] Great. Would you have any final words for our listeners? Maybe something that you think is an important message to get across that that hasn’t come up yet?

Linnea Fletcher: [00:35:54] I think a final word for our listeners is I’ll share with your listeners the one thing that got me involved in education when I moved from research to education was the realization that the most important resource that we have in this country in the world is our students, our children. So why aren’t we doing more to engage them in what are real projects? That’s the way it used to be. That’s the way it was when people were on the frontier. That’s what they do in apprenticeships in other countries and we are doing in the US too. But the best way to educate people is not in a textbook, or at least not completely in a textbook, but in a lab and using exactly what they use in industry and in research. That’s when students really appreciate their education and their interest in science is have them do the real thing. And we should be doing more of this, not less.

Grant Belgard: [00:37:04] I couldn’t agree more. Thank you so much for your time. It was really great chatting.

Linnea Fletcher: [00:37:09] Thank you. I enjoyed speaking with you.

The Bioinformatics CRO Podcast

Episode 52 with Yuri Deigin

Yuri Deigin, co-founder of YouthBio Therapeutics, discusses developing rejuvenation gene therapies based on partial reprogramming and his role reinvigorating investigations into the origins of SARS-CoV-2. 

On The Bioinformatics CRO Podcast, we sit down with scientists to discuss interesting topics across biomedical research and to explore what made them who they are today.

You can listen on Spotify, Apple PodcastsAmazon, and Pandora.

Yuri Deigin photo

Yuri is co-founder of YouthBio Therapeutics, a company developing gene therapies for rejuvenation.

Transcript of Episode 52: Yuri Deigin

Disclaimer: Transcripts may contain errors.

Grant Belgard: [00:00:00] Welcome to The Bioinformatics CRO Podcast. I’m Grant Belgard and joining me today is Yuri Deigin. Yuri, can you introduce yourself please.

Yuri Deigin: [00:00:08] Sure. Thank you for having me on the podcast. I’m Yuri. I’m a drug developer. I’m leading a longevity company called YouthBio. We are developing in vivo partial reprogramming gene therapies to ultimately create rejuvenation therapies, but in the interim, create therapies against existing age related diseases like Alzheimer’s, for example. Happy to chat about any topic today.

Grant Belgard: [00:00:36] Yeah, I’d like to learn more about YouthBio and how related do you see the the underlying causes of various age associated diseases?

Yuri Deigin: [00:00:47] All right.

Grant Belgard: [00:00:47] How much convergence do you think there is?

Yuri Deigin: [00:00:50] Yeah, right into it. I guess YouthBio is really the culmination of most importantly, my understanding of how aging works and that is epigenetically driven and that obviously all age related diseases in my mind are caused by the underlying process of aging. And of course different diseases could be different manifestations of the same process or different results of this process of gradual epigenetic slowing down of the repair systems and all other systems that help maintain homeostasis. And so reprogramming is one way to actually intervene on a level of epigenetics, because while reprogramming just epigenetically brings the gene expression pattern all the way into the embryonic like gene expression pattern. And that results in all of the changes associated with cell morphology and function ultimately as it’s of course driven by gene expression. But it all starts in changing the gene expression pattern. And what was noticed that during the reprogramming process, the cell is also rejuvenated both physiologically on the level of its transcriptome basically on the level of gene expression. In the initial stages of reprogramming, it seems that the pattern of the gene expression of an old cell gets shifted closer to a pattern of gene expression of a younger cell, the cell of the same cell type. And so this is really the foundation of partial reprogramming where we try to use this process of rejuvenation during reprogramming and stop it at that precise moment where the cell still remains of the same cell type that you start with. But it gets rejuvenated to some degree.

[00:02:38] And we don’t want the reprogramming process to proceed further because that could make the cell lose its function and lead to all sorts of problems. So that’s the partial aspect of partial reprogramming. And yeah, basically the underlying assumption, underlying hypothesis that aging is epigenetically driven, really synchronizes well with the approach of reprogramming, which as I mentioned works on the level of epigenetics. And that’s why I think it’s a very powerful paradigm. If we can figure out how to do this safely in all sorts of different cell types, because I think it actually is necessary, like different cell types necessitate different approaches to using reprogramming in those cell types, then I think we can have very powerful instruments to rejuvenate those cell types. And so eventually have a systemic therapy where you can target multiple cell types, multiple organs and eventually obtain this holy grail of systemic rejuvenation and make aging either slow down or even reverse aging to some degree in healthy people. That’s the ultimate goal of longevity research to make healthy people healthier for longer and make aging slow down in healthy people and radically extend lifespan and healthspan using such approaches.

Grant Belgard: [00:03:55] How do you think about aging fundamentally and what is the relationship between that and the epigenomic changes that are associated with aging?

Yuri Deigin: [00:04:05] Yeah, it’s a very interesting question because just recently we had a discussion on what is aging for a while. I think it’s been spearheaded by Vadim Gladyshev. And just recently we had another installment, his talk on the topic. So it’s actually interesting that there isn’t a consensus or at least a complete consensus in the field on what aging is exactly, because different people call different things, aging. And obviously there’s some common things that we observe that we realize is what aging is associated with. We all know aging when we see it. We know an old person from a young person. And even non-experts in gerontology, like people obviously are very good at telling apart an older person from a younger person. So obviously we have that really actually deep down in genome recognizing aging and recognizing old individuals from young individuals, even across species. So this is obviously something very fundamental to life, to what we will at least guess mammals and higher animals recognizing old from young. But on the level of gerontology and biology, I think to me, aging was just the process that causes mortality risk to increase with time. So basically, if your mortality risk does not increase, to me that means the organism is not aging. So if the mortality risk stays constant or actually decreases with age, then that’s an example of either a non aging organism or a non aging stage in the life history of an organism.

[00:05:44] For example, I think between ages like 5 and 8 or 5 and 9 in humans, the mortality risk actually decreases and reaches a minimum between ages like 8 and 10. And then after puberty starts, then that mortality risk starts to increase and it keeps increasing exponentially until we die with potentially a plateau between like age 20 to 30, 35. Some gerontologists actually argue whether there is a plateau or there is a slow down or there isn’t, or just an aberration or statistical aberration. But basically this is just, I think, one key observation or definition even of aging. Basically, aging is the process that increases mortality risk. And in humans, of course, it doubles mortality risk every eight years. So it’s an exponential increase. And in other animals, it’s not necessarily. So in some animals, actually, the mortality risk decreases with age. There’s examples of turtles, for example, who seem to have observed, we observed, decrease in mortality risk and actually increase in their fertility in some species of turtles. But of course, there are other ways to define aging as, for example, accumulation of various damage, intracellular extracellular or other manifestations, other hallmarks that people associate with aging. And they call that the aging process rather than the downstream effect of increased mortality. So as any academic field, you can have a lot of debate about the precise details ultimately coming, circling back to what we were starting to discuss in the beginning of this question. We obviously know aging when we see it and we would know rejuvenation when we see it.

[00:07:29] If you are able to take a 40 year old person and rejuvenate him, her to look and act and physiologically be the level of a 20 year old or say any two numbers, obviously everybody would agree that that is true rejuvenation. And you can do this, of course, in other animals as well. Mice, for example, two specialists in mice would obviously see rejuvenation. If you take a two year old mouse and rejuvenate to a little one year old mouse, there won’t be any question that this is actual rejuvenation. So from that standpoint, you can have and obviously there’s other biomarkers of aging. I think right now there’s physiological biomarkers of various functions of the organism like lung function, kidney function, heart function. There’s also epigenetic biomarkers are built on the known data of health status, mortality and all sorts of different ways that you can approximate the aging process and evaluate whether you’re able to observe a slowdown in the aging process or actually a reversal of the aging process. If you see, for example, biological age being reduced after some interventions. Sorry, I think I’m starting to maybe go a little bit off.

Grant Belgard: [00:08:39] No, this is good. It kind of raises a natural question. How do you think about aging and biomarkers of aging in the context of drug development? Because certainly different stages you would need to consider different things. And how does all that tie into the question of what is aging? Is that question essentially more of an academic debate or would it really impact at a fundamental level what your primary endpoints would be in a clinical trial?

Yuri Deigin: [00:09:15] I think we have at this point, enough biomarkers to assess to a pretty good degree any interventions that claim to rejuvenate or slow down aging precisely because we have different biomarkers and we can test function and we can test epigenetic age. So from that standpoint, I don’t think there’s anything limiting drug development or therapy development for rejuvenating therapies, especially because at this point and in this regulatory framework or regulatory landscape, you really need to go after interventions after diseases. Interventions have to go after diseases. So it’s not like you can have clinical trial of a healthy taking some sort of rejuvenation therapy and then measure endpoints. You really need to have some patients that you administer the therapy to, and then you evaluate clinical endpoints and biomarkers that are improved by that therapy from that standpoint.

Grant Belgard: [00:10:16] What indications do you think would be especially promising for that as a gateway to ultimately develop drugs that more generally target aging? How would you think about starting?

Yuri Deigin: [00:10:31] Well, we have examples of senolytics and osteoarthritis of the knee. People thought that would be a good indication to try. And I think there’s different ones that you can go after. And well with the metformin trial is another methodology where you have a whole basket of age related conditions and you have people susceptible older people to those conditions. And you then evaluate whether your therapy, your drug metformin in that case is able to reduce the incidence of a number of age related conditions. That’s one way to actually measure the effectiveness of a potential therapy. And other therapies. I depending on the actual intervention, they could have different optimal targets, optimal diseases, which could be the first ones to go after in a clinical setting. Reprogramming is if we’re talking in the context of partial reprogramming, I think it has a whole host of different areas in which you could demonstrate benefits in that particular disease model or actual disease or predisposition to disease, where you can confidently say that not only is this helping this particular disease, it could also have a systemic effect if you’re able to target multiple tissues. In the context of reprogramming, skin is people think is a low hanging fruit because you can have very quick results, visually observable improvements.

[00:12:02] And that’s why I think a couple of companies are going after skin, are going after dermatology. And also other areas in terms of hematology and immunology, people are also considering. But also I think in the context of the central nervous system, brain diseases, if you’re able to demonstrate using approaches of partial reprogramming, even a slowdown in the onset of various neurodegenerative pathologies like Alzheimer’s, Parkinson’s, etcetera, then it’s a very compelling. Again, very compelling case to be made that this is truly a therapy that’s at least slowing down the onset of aging in this particular tissue, the onset of age related symptoms of this particular disease. And also even if you’re able to reverse the symptoms, that’s a much more stronger case that you’re actually rejuvenating the underlying organ. So I think, yeah, while they’re very neurodegenerative diseases, they’re obviously hard nuts to crack. I think the upside in their cases is really high because there’s huge unmet clinical need and Alzheimer’s, for example, you’re able to demonstrate clinical benefit there that could be very compelling case for people to take notice that this approach is very strong, rejuvenating approach.

Grant Belgard: [00:13:23] So I think neurodegeneration is a really good use case because we do know there is some degree of genetic overlap, several neurodegenerative diseases and also gene expression signatures associated with age and then GTLS for those and so on have been identified in the context of brain age. What concerns me a bit though about the paradigm of slowing aging overall and having a substantial impact on the rate of age associated disease is as if there were a single underlying factor of aging that affected overall physiology in a similar way, something analogous to G and intelligence or whatever, you might expect to see that in genome wide association studies of different age related diseases in different organ systems. And to have some of the usual suspects coming up time and time again and within certain classes of diseases of course. You see some of that neurodegeneration tau, for example, comes up quite often, but you see very, very frequently, which you would expect if you have age matched controls versus people with this disease or that disease. On the other hand, of course, there are many facets of age associated biomarkers that are strongly correlated with one another. So these frailty indices and so on. And of course we do have genetic associations with measures like that. So do you think about it as, okay, we will identify treatments that are effective for maybe somewhat broader classes of diseases and reducing the rate of onset? Or do you think there is a good possibility of slowing everything down together?

Yuri Deigin: [00:15:38] I think theoretically there is a good possibility of slowing things down together. I think aging is centrally regulated, to be honest. I think actually it’s a program and I know I’m a minority opinion on this because there’s so many life stages that are definitely centrally regulated. And we have to have in a very coordinated concert to be developing just at the right time and the right proportions to have an embryo develop properly and also to have puberty onset at the right time and all organs start growing at the right time. So there is obviously a central synchronization mechanism. Now we still haven’t figured it out how exactly it occurs and well, there are some hypotheses that the hypothalamus could be one such controlling master regulator of aging because it is actually controlling a lot of daily monthly processes or maybe even on a longer time scale obviously. During embryogenesis it plays a very important role. That said, I think this is a parallel search for this master synchronization system. And also, of course, I think if we were able to slow down development, we see that that obviously slows down aging or actually puts aging on pause if we’re able to delay the onset of sexual maturity. And actually some people are pursuing that as a rejuvenation strategy. There is a gerontologist in Ukraine, Valerie Golub, who’s studying this in rats and reptilian, trying to see because obviously we’ve seen in many organisms that neoteny greatly extends lifespan and also experimentally, if you’re able to pause development or slow down development, that also extends lifespan. And it seems to put aging on pause.

[00:17:35] But coming back to the partial reprogramming approach, it’s a bit of a different way of going about it. It’s just targeting key organs that are playing the biggest role in our age related pathology of course. Heart disease being one of them and other organ systems and hoping that we can target enough key organs and key systems to that result in a systemic effect where we can slow down aging of the entire organism enough to produce sizable gains in healthspan and lifespan. But also there is a hope and a hypothesis that we’re also exploring that maybe by modulating in certain areas of the brain, rejuvenating them, maybe we can then achieve systemic effect. But obviously that’s just a hypothesis that we need to explore. But to answer your question, I do think that it might be possible to have an intervention going at the entire aging process, or at least the actively driven aspect of the aging process, because obviously after some time there are also stochastic things happening that are not part of the epigenetic landscape being driven, but they’re side effects of genes allowing stochastic changes to produce enough damage that it actually starts to accumulate. But that’s a bit of another tangent that I’m happy to explore.

Grant Belgard: [00:19:15] There are maybe a couple of tangents we’ll go off on in a bit, but I think it’d be really interesting to hear about your journey, How did you end up here? What drove you in the direction of science etc?

Yuri Deigin: [00:19:28] Oh yeah. My journey to longevity started with just a regular drug development and meeting people who are also wearing the same drug development ecosystem. But there were also longevity minded people who just shared with me the idea that aging is the causal factor in age related diseases that I was working on. They were working on Alzheimer’s, for example, and basically saying that we can and should try to intervene in aging and slow aging down and ultimately, hopefully reverse it. And that was a revelation at the time to me because as most people unfortunately on the planet, I never thought that aging is something that needs to be intervened in or should be, or is it possible to be intervened in? I thought aging is inevitable, just everything ages and didn’t even think that there is something that could be done about it until my eyes were opened by my friends at the time. And obviously after they made me aware of this whole industry and research community looking into aging, fundamental mechanisms of aging and trying to intervene in aging, that very quickly I realized that it makes all the sense in the world that, yes obviously aging is the causal factor in all those diseases and there is no good reason why we should settle for the lifespan that we inherited biologically from our ancestors. And we have the intellectual capacity to analyze biological processes and finally have the tools to intervene in biological processes that it only makes sense for us then to turn our intellect and our abilities to intervene in biology to the biggest limiting factor in our lives, which is aging.

[00:21:24] And very quickly, I became a very passionate activist at first about aging research, about the necessity to research into aging and just trying to open other people’s eyes, just like my eyes were opened by very, very simple and logical information and just making people aware that there is a thing like aging research out there that it’s possible to intervene in aging. It’s possible to extend lifespan in model organisms. It has been done many times and it’s only a matter of time until we find effective interventions that can be applied to humans and produce sizable gains in both health and lifespan. And eventually I was able to then not only do the activist part, but do the drug development related or start doing drug development related to longevity. And that came in the context of partial reprogramming, because at the time when I learned about partial reprogramming, I was already of the mind that aging is driven by epigenetics. To effectively intervene in aging, we need to intervene at the level of epigenetics if we’re talking about already formed organisms. Of course, if we’re talking about new organisms, probably we can intervene at the level of the genome.

[00:22:39] But unfortunately we’re already cooked organisms using the cooking instructions stored in our DNA. So if we want to change something in our biology, we have to go after gene expression. And as I mentioned in the beginning, partial reprogramming is one way to intervene at the level of epigenetics, at the level of gene expression. And it’s a very effective mechanism because it uses an underlying process that’s already fortunately encoded in our genome to do this, to restore gene expression of the primordial embryonic stem cells. And it’s a very powerful tool that we can use to to essentially hack for our purposes, to rejuvenate adult organisms, adult cells. And yeah, I started on the path to try to translate this paradigm into therapies very early on back in 2017. The paper came out in December 2016, and then I founded the first company in Ethereum dedicated to translating this paradigm in the summer of 2017. I got really excited about it because it fell on fertile soil in my mind, that partial reprogramming paradigm, because I already thought that epigenetics is the driver of aging. So again, I took a little longer maybe than I should have to answer your question. But yeah, happy to dive into any details of the journey or any particular aspects of it that could be useful to other people.

Grant Belgard: [00:24:10] Yeah. I think it’ll be interesting to hear about the lessons you’ve learned through that. But before we get into that, to go on a bit of a tangent, you’re obviously quite early to this. And of course now partial reprogramming and aging research is much more mainstream than even five, six years ago. But you were also very early on the important aspect of coronavirus Can you tell us about that and how did you get there? I recall reading your very, very long blog post years ago, and I was really impressed, what was the impetus behind that? Because at the time that was very, again not mainstream but it’s one of those things that has become much more mainstream in the years since, in large part because of what you kicked off.

Yuri Deigin: [00:25:09] Yeah. It was just another tangent essentially that I got curious about. The origin of the coronavirus, COVID, I guess not just any coronavirus, but the coronavirus that caused the global pandemic. Basically like everybody else was curious in early 2020 where the virus came from, and initially a lot of people made the obvious connection that Wuhan has the premier lab in Wuhan Institute of Virology that has been studying coronaviruses. But in the very early stages of the pandemic, this making the hypothesis that the lab had something to do with the outbreak was considered a crazy conspiracy theory. And the powerful and very respected scientists were putting their names and their reputation behind this to dispel this conspiracy theory. And initially I just trusted them. I thought hey, if nature medicine says that the virus must be natural and there’s like 5 or 6 virologists and Anthony Fauci saying, that there ought to be listened to, then they know what they’re saying. And but at some point just decided to dive a little deeper. And instead of just outsourcing my thinking to them, decided to try to see for myself from first principles. Does it make sense this conspiracy theory makes sense or not? And so I read the Nature Medicine paper, and I was a little disappointed by the logic because once you strip out all the virology lingo, you’re left with very unconvincing logic that basically it’s the absence of evidence that the authors are trying to sell as evidence of absence, evidence of possibility that this could have come from a lab. And then I started digging deeper and I saw that the research that they were doing in Wuhan was exactly potentially similar to what could have produced this coronavirus.

Grant Belgard: [00:27:25] And of course, this was long before the diffuse proposal had come out and so on.

Yuri Deigin: [00:27:29] Oh yeah, yeah, yeah. Diffuse was a year afterwards and yeah, basically it was just circumstantial evidence of look, this is clearly a huge red flag that the lab that’s been collecting coronaviruses from all over the world and manipulating them in all sorts of ways had the outbreak of this coronavirus with the very unusual feature, a couple of unusual features, one of them being this furin cleavage site. And it was very suspicious to a lot of people. And basically, yeah, I wrote this up in the blog in like early 2020, published it, and then it took on a life of its own and got me deeper into the rabbit hole and into the community of people, like minded people who were also very suspicious that this could have come from a lab and were continuing to investigate all aspects of everything surrounding basically the outbreak, the work in the Wuhan virology and other EcoHealth Alliance as well of course, what their involvement was and how they were using grant funding and their close cooperation with the Wuhan Institute of Virology and other labs to essentially collect and manipulate viruses in the lab to make them more infectious for the purposes of assessing how dangerous this would be if it happened in nature. Basically try to second guess or try to guess what nature could do to make viruses more dangerous for humans. And they did this with SARS like viruses. They did this with MERS like viruses, MERS being the Middle Eastern respiratory virus that is very deadly. It’s like a 37% fatality rate. And actually they did a lot of research on that in Wuhan Institute of virology together with EcoHealth Alliance as well.

[00:29:19] We learned that a year or two well, not to a year and a half after, of course, the initial outbreak because of all the Freedom of Information lawsuits that were filed to NIH and other agencies to actually see what has been going on in this research between EcoHealth, NIH, who funded a lot of these studies, and the Wuhan Institute of Virology, who were doing a lot of these studies, but again diverged. But yeah, basically once I gotten interested in this origin of coronavirus, the community of other people that I got together involved with we, started calling ourselves drastic. It was a Twitter based group of activists trying to investigate the origins of the coronavirus. And we investigated some additional aspects, published a bunch of papers on very suspicious discoveries. And basically, at some point, yes, the diffuse proposal was leaked by drastic. The diffuse proposal being, of course, the joint grant proposal by EcoHealth and the Wuhan virology in which they pitched to DARPA this idea of collecting novel SARS like viruses and also engineering novel furin cleavage sites in sites like viruses, because up until now and actually never since SARS, like viruses, never had a furin cleavage site at that spot. And it seems actually to be evolutionarily discouraged in bats because in bats, these viruses are gastrointestinal viruses and furin cleavage sites actually seem to be detrimental to the viruses being tropic to the GI tract or something. Basically, furin cleavage sites for some reason make viruses more preferential to the respiratory system. And but of course, for humans, that’s the biggest way how viruses get transmitted through the once they’re airborne through the respiratory system.

[00:31:22] So for a virus to jump from bats to humans, the key skill for it to pick up is to actually become tropic due to our respiratory tissues and cell types and inventing or getting a furin cleavage site actually is a catalyst for a virus to do that. It basically turns the virus from a gastrointestinal virus into a respiratory virus, and that makes it very high threat for transmission. It makes it so much more transmissible for humans, especially. And in the context of research on coronaviruses, it’s been very well known that the furin cleavage sites expand tropism of such viruses and make them actually respiratory viruses. And it’s been experimented with other virus types, coronavirus types to engineer novel furin cleavage sites and observe how that changes the tropism or the preferences of the virus to different cell types and different systems, including the respiratory system. And so in that diffuse proposal, one of the things they described to put in their experimental roadmap was to try introducing novel furin cleavage sites, basically to assess the risk of how likely it is in nature for a furin cleavage site to arise and to also model what would happen if a particular virus got a furin cleavage site. How likely would it then be to jump to humans? And of course the SARS-CoV-2 virus has this receptor binding domain that’s very highly preferential to human ACE2 receptor, which is very, very interesting characteristic. It scores like number one on the list of all different animal ACE2 receptors to be preferential to the human ACE2 receptor, which is very odd for a bat virus. But maybe there’s a species of bats who has a very similar or an ACE2 receptor that’s also very high binding affinity to that particular conformation of the spike protein on the SARS2 virus. And of course, not only does the spike protein binds well to our ACE2 receptor, the furin cleavage site makes it so much more transmissible and so much more preferential to our respiratory system. And so once the DEFUSE proposal was publicized in the summer of 2021, to a lot of people, this was very convincing additional nugget of evidence.

Grant Belgard: [00:33:49] That was what pushed my posterior probability on this way over 50%. I recall reading through it and saying some words that would not be appropriate for a family podcast. It was just shocking. And I was certain at that point that these surely global regulations on gain of function research would be coming down swiftly. And the amazing thing is, even though later that summer, we got to the point where most Americans believe, WIV was the origin of the virus. And of course former CDC director during the outbreak said something along those lines. Obviously a lot of people within the US intelligence community were concerned that was the case and several people in Congress. So one would think something would have been done about it by now. What’s shocking is there’s probably more manipulation of coronaviruses happening now than before. It’s extraordinarily dangerous. I mean, even if you don’t buy that it came out of WIV like surely even without that, just knowing how common it is for viruses to escape from laboratories and so on, the cost benefit of this kind of work is so overwhelmingly on the cost side and not the benefit side.

Yuri Deigin: [00:35:18] Yeah, for sure. And yes, the SARS-CoV-2 escaped definitely once from the Taiwan BSL-3 laboratory and there were actually acknowledgments in internal emails that before that escaped within a Chinese laboratory. And the first SARS virus that was much less transmissible escaped four or six times from different labs. So coronaviruses obviously can escape from even high level of security biosafety labs. So and yes obviously, I’m sure there’s countless times where people were infected handling coronavirus samples these days because so many labs now work with the coronavirus. And obviously it’s so hard to track now where the infection you got as a researcher is from a lab or just somewhere outside. I mean, in Taiwan, they could track it down because essentially it was very low circulating SARS-CoV-2, if not zero at that point. And they were able to genomic tracing to confirm that this particular sample is the one that infected the researcher. But yeah, also all sorts of potential gain of function research that people have been doing or are doing now with the COVID virus, SARS-CoV-2, one of the earliest ones was these Italian researchers in Siena. I think in the beginning of 2021, they passaged SARS-CoV-2 in the presence of neutralizing antibodies from people who had COVID or were immunized to actually see how it could evolve to escape those immunity escape, that antibody immunity.

[00:37:01] And they succeeded. They created a whole new strain that was very good at infecting people who already had immunity to the original SARS-CoV-2 virus. If that escaped, we could have had a whole new episode of the pandemic with a whole new strain. And what happened with Omicron to me is highly reminiscent or highly similar to what could have happened if a gain of function research could have produced a strain, then just got out and infected people and started circulating. Because Omicron is just so different from its last known ancestor, it has like 30 spike mutations basically like that. It developed seemingly without any intermediates. And like to this day, it’s still a mystery. How did Omicron arise and where was it circulating between like June or November of 2020 when its last ancestor was seen in November or December 2021, when Omicron emerged. Where was it all this time? And the idea that it wasn’t just someone immunocompromised patient in which it could have developed those 50 mutations, including 30 spike mutations.

[00:38:17] To me, it’s a very implausible hypothesis because we have been observing quite a number of immunocompromised patients and in none of them did we observe such a huge number of mutations arise. There’s usually a couple of dominant ones arising and then maybe a few others. But I think the most we’ve seen is like ten mutations in the spike of a person who had like 18 months infection present for a duration of 18 months, they couldn’t clear. And so but now we in Omicron, seemingly between a year since seeing its last ancestor developing 50 mutations with 30 spike mutations, it’s really, really crazy. So yeah, it could have been a lab leak as well. And who knows what other gain of function research is going on because obviously it’s not a regulated space. And even if you regulate it in one country, who knows what happens in countries that are not signed on to be parts of some regulation. So it’s a huge, huge existential level problem for us, for humanity, that unregulated gain of function research of pathogens going on in all sorts of labs all over the world could lead to pandemics, maybe even worse than this one, I hope not.

Grant Belgard: [00:39:32] It’s just wild to me like when I was reading the DEFUSE proposal, one of my immediate thoughts was this is kind of the Manhattan Project moment for the life sciences, except far more people have been killed by this than have been killed by nuclear weapons. So I was expecting surely there would be.

Yuri Deigin: [00:39:51] DEFUSE proposal was actually much broader than that. They proposed actually creating vaccines for bats with which they would go out into the field and immunize bats preemptively. And who knows what wrong could have gotten from that approach. And you know what? Maybe new combinations of viruses, bats could have developed due to that thankfully DEFUSE proposal was not funded. And that particular aspect of it of trying to actually go out and change ecosystems with preemptive vaccines in wild animal populations. This was criticized by the reviewers, but of course the molecular biology experiments, even if they weren’t funded by DARPA, they could have been funded by many other agencies, including Chinese funding agencies or even like you don’t need a lot of funding to do genetic manipulation of viruses if you already have the viruses and you collected some and to insert 12 nucleotides into a coronavirus genome doesn’t really take a lot of money or a lot of time for your post-docs or PhD students.

Grant Belgard: [00:41:00] Why do you think there hasn’t been a reckoning on this? Most people believe this is what happened. Plenty of people in power have said this as well, and yet there hasn’t been an aggressive effort to shut this down.

Yuri Deigin: [00:41:16] Oh, like to shut down gain of function? I mean, yeah, it’s very hard, I think, to come up with novel global regulation of an entire field of virology. If we’re talking about pathogen research and classifying what exactly is gain of function for a pathogen and what isn’t and in what context it should be permitted or should it be like completely banned? And what about places that don’t sign on to this convention? Virology is just going to migrate or virology labs will just migrate to those geographies that don’t have that regulation. Of course, if you ban it in the United States and Europe, that’s the major sources of funding. So I think that could lower risks of various pathogen gain of function research ongoing and greatly decreased in number.

Grant Belgard: [00:42:08] But I guess the challenge is, it’s much more inexpensive and widely accessible to do this kind of work than it is to enrich uranium and build nuclear weapons.

Yuri Deigin: [00:42:19] Oh, yeah. These days, absolutely. Biology, I think from an existential risk perspective, is much higher on the list than nuclear war or nuclear terrorism, because bioterrorism by comparison is much cheaper unfortunately, Hopefully, we won’t have bioterrorists listening in and like, Oh, okay, I was enriching uranium in my backyard. I think I’ll go build a virus lab now. But I think the process is actually ongoing. It’s slow and we see some of it starting to happen with now the Republicans having these hearings and maybe they will result like there’s two two questions. One is about the origins, which is of course important. But it’s not like even if we don’t find out the exact origin.

Grant Belgard: [00:43:11] Even if we’re not certain, certainly I think it’s undeniable that it’s a very plausible source. And even in light of it being a plausible source, it very clearly is something we need to button up and make sure that that thing does not happen. Or even if you say it didn’t happen the first time, that it doesn’t happen in the future, right?

Yuri Deigin: [00:43:34] I mean, yeah, not like just the SARS leaks I mentioned happening in the past couple of years. And just before the Wuhan outbreak, there was a brucellosis outbreak in China, in Kunming, in Yunnan, in the lab, and like 100 people got infected by it’s much less transmissible, thankfully, bacterial infection, but still, obviously it’s a lab borne infection. So these things happen and these things are dangerous. It’s just a matter of the right pathogen escaping that could be so much transmissible that it could cause a pandemic versus something that isn’t. But yeah, absolutely should be taken seriously. And I think also the problem is that politicians are blissfully ignorant on where biology stands right now. And when they find out their hair stand up how easy it is to manipulate biology and how cheap it is these days. And basically what Wild West, to quote Jeremy Farrar exists in all over the world in labs. Basically what I mean, nobody is regulating what you can do in the lab. If you want to supercharge a virus, the virus police won’t come and say, Why did you do this? Didn’t you realize that this is dangerous? So, yeah, hopefully soon enough, people in power will come to understanding of what’s going on and what’s possible and what’s dangerous.

Grant Belgard: [00:44:58] If someone is just hellbent on doing it, it would be difficult to stop them. But certainly the vast majority of the work ongoing where something like this could accidentally get out and cause lots of problems. It’s funded by funding agencies. People are doing it to publish work that’s peer reviewed. If there were a common consensus even if scientists just got their act together and did this even without any kind of government intervention, that would dramatically reduce the likelihood. But that doesn’t seem to be happening.

Yuri Deigin: [00:45:38] Yeah, exactly. And yeah, I think the incentives are misaligned here because there in order to publish something we have in virology. You have to create interesting research. And right now it’s very hard to do interesting stuff without genetically manipulating viruses or modeling some different changes that could make viruses more pathogenic or more transmissible. I think so. But at the same time, from the benefit of society or humanity as a whole, this type of research supercharging viruses or creating more transmissible viruses or more dangerous viruses, I think has a very, very little benefit, if any. But at the same time, the risks are huge and the risks are obviously shared by the entire world. And so if we’re worried about just one bioterrorist, it’s one thing. But if we’re worried about thousands of virologists doing this thing and making some mistake or not even a mistake or just supercharged virus could escape, even if they follow procedures, maybe some equipment malfunction or something happens that people don’t anticipate, that could lead to a pathogen to escape then the probability of this if a thousand people are doing it versus just one crazy terrorist is doing it, I think are much higher. That’s a different conversation.

Grant Belgard: [00:47:06] So I guess coming back now after, I think it was a pretty interesting digression in your own career, kind of a side project. So if you could go back several years before you started the founder journey, what advice would you have for yourself?

Yuri Deigin: [00:47:25] Oh, that’s a tough question. Invest in Bitcoin maybe. That’d be one advice. I mean, like if we’re talking something useful for people these days who are entering longevity, like in terms of career advice, I think now is a much better time because there’s all sorts of fellowships and programs like LBF Longevity Biotech Fellowship available for people who are just getting interested in longevity and want to quickly orient themselves. I think the number of resources available is really large compared to Decade ago or more when I was entering the field. So just the advice would be to study existing description of the landscape of the field and various areas of research and just, not be afraid to reach out to people and ask for advice if you’re interested in career switching. There’s all sorts of companies open to people coming from different fields. And obviously, if you want to do this, if you’re interested in longevity, one advice I would give is not to defer, not to procrastinate, but to get into it as quickly as possible. Because I think the more you get drawn into a career, the harder it is to to switch over. And longevity, I think right now is at a good point where you can enter into a lot of new companies or even labs on the academic side and the tidal wave that’s coming, it’s going to lift your career and your progress in this field as well. So maybe just don’t delay.

Grant Belgard: [00:49:06] Yeah, it’s interesting because you had a somewhat circuitous path where you were in tech for several years before getting into pharma.

Yuri Deigin: [00:49:17] Oh, yeah. Before drug development, I was in tech. My first career was in tech and I did computer science degree in mathematics and yeah, I worked for IBM. I did a startup actually in mobile applications back in like 2002 before it was cool, but I pivoted then into drug development. I wanted to do drug development for a while. And actually the time has come back, like in 2008 for me to do this. So I decided to do an MBA to help me get into the pharmaceutical business development, and that was the key pivot. But then to get into longevity drug development, that took me also some time before an opportunity came, which I think was a perfect opportunity with partial reprogramming because it was just the right approach for my current and then understanding of aging as an epigenetic process.

Grant Belgard: [00:50:11] Well, I guess in terms of getting it early, you’re two for three. So longevity field, the COVID origins, but not Bitcoin.

Yuri Deigin: [00:50:21] Oh yeah, yeah. There’s a lot of other investments that if you had hindsight, it would be nice to know about back and a decade ago.

Grant Belgard: [00:50:31] Cool. Is there any advice you would give to people who are launching their first company network?

Yuri Deigin: [00:50:40] I think yeah, networking is really, but obviously it’s pretty obvious advice and don’t get discouraged because it’s very easy. As an entrepreneur, there’s always a roller coaster. There’s always going to be down times where you think everything’s going badly, but you just have to keep going and keep the faith that eventually there’s going to be another positive development that will, and like longevity in terms of being an entrepreneur is also very important. You have to keep doing what you’re doing and if you believe in it. Of course, if something changes and you realize that the business model you had was wrong or the therapeutic approach you were exploring doesn’t really work out, then of course you have to change. But if all the fundamentals remain the same and it’s just the environment is not really good, like right now, economy is not great. So a lot of pundits are saying there’s going to be like an extinction of company of startups coming. But do you have to close yourself to the noise and just keep doing your job and just try to achieve your milestones that you put forth for yourself and for your company. It’s probably the same advice everybody gives.

Grant Belgard: [00:52:06] No. I mean, it’s good to know what people emphasize because there aren’t enough hours in a day to do everything one is advised. And so even hearing the same thing time and time again, you get extra votes for the importance of that.

Yuri Deigin: [00:52:26] Yeah. I think everybody says resilience is a key attribute for entrepreneurs and that’s true.

Grant Belgard: [00:52:33] Get punched in the face.

Yuri Deigin: [00:52:35] Yeah, exactly. But it’s true. You have to keep going in the face of adversity. And of course, also the more you do it, thicker your skin becomes and the better you become at managing it. So also, yeah, I think for younger entrepreneurs it could be a little tougher, but it’s just something like with anything else with the time and practice, you get better at it.

Grant Belgard: [00:53:03] You develop thick skin.

Yuri Deigin: [00:53:06] Yeah. Stick to it. Don’t get discouraged. And also, yeah, I think it’s also important to have people who can help you both emotionally and with advice and like, support groups are important. And that’s why I think also within the fellowships like the ODLB Fellowship or the Longevity Biotech Fellowship, these mastermind groups as you know, they could be very helpful because there you can connect with people going through similar things, similar entrepreneurs or scientists, researchers or postdocs going through similar adversity and connecting with them and getting support, both emotional support or just some advice or some other help. I think it’s really important to have that kind of support structure, support network for everyone, entrepreneurs and academics alike. So yeah, get that support structure in place, network and try to form this group of people who can support you through the tougher roller coaster rides.

Grant Belgard: [00:54:04] Solid advice. Thank you so much for joining us, Yuri. It’s been a pleasure.

Yuri Deigin: [00:54:10] Thank you. For me as well. Hopefully it was useful for the listeners. So thank you.