#382 Stem Cells and Type 1 Diabetes

September 16, 2020Scott Benner

Jeffrey R. Millman, PhD

After reading an article about stem cell research, Scott invites Dr. Jeffrey Millman onto the show to talk about stem cells and Type 1 diabetes. Dr. Millman discusses how he and his colleagues developed a protocol for generating functional pancreatic beta cells in vitro from human pluripotent stem cells. In this episode, Dr. Millman describes the fascinating research currently being developed at the Millman Laboratory at Washington University School of Medicine in St. Louis.

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DISCLAIMER: This text is the output of AI based transcribing from an audio recording. Although the transcription is largely accurate, in some cases it is incomplete or inaccurate due to inaudible passages or transcription errors and should not be treated as an authoritative record. Nothing that you read here constitutes advice medical or otherwise. Always consult with a healthcare professional before making changes to a healthcare plan.

Scott Benner 0:06
Hello friends and welcome to Episode 382 of the Juicebox Podcast today, my guest is Jeffrey Millman. Jeffrey is a PhD. He's a researcher, and he is working on some very interesting stuff regarding Type One Diabetes that I think you're going to enjoy hearing about. I reached out to Jeffrey, after reading an article online that started off by saying new technique efficiently converts human stem cells into insulin producing cells, I thought, well, that's interesting, and seems like a leap. I reached out to Jeff, and he was kind enough to come on the show. Best thing about him is that as he's explaining all of these, what I'm going to tell you are pretty technical ideas. He does it in a way that you can understand. I mean, I understood it, so I'm assuming that means we all can. Please remember that nothing you hear on the Juicebox Podcast should be considered advice, medical or otherwise, please always consult a physician before making changes to your health care plan. We're becoming bold with insulin.

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I have a handful of questions, but mainly, I just like to hear your thoughts.

Jeffrey R. Millman, PhD 5:35
Yeah, I appreciate the invite. And one of the things that we try to do over here is to reach as wide of an audience as possible. And so I view this as a good opportunity to reach further into the Type One Diabetes audience. Hi, my name is Dr. Jeffrey Millman. I'm an associate professor of medicine and Biomedical Engineering at the Washington University School of Medicine. My lab uses sim cells for the study of treatment of diabetes, and I'm very happy to be here today.

Scott Benner 6:05
Thank you so much for doing this. Okay. How do we do this? am I calling you Jeff Jeffrey. Dr. Millman, what do you like?

Unknown Speaker 6:12
Um,

Jeffrey R. Millman, PhD 6:13
I would say,

Scott Benner 6:15
Jeff, would probably be best. Hi, Jeff. Well, I'm Scott. And I saw an article that was floating around in the news. Let me see if I could be more honest than that, Jeff. There's the thing that I think of is cure season, where everyone floats their research out as far as they can, I always assume they're looking for more funding. And it has this sort of unintended consequence of reaching newly diagnosed people who think that they've been diagnosed just five seconds before the cure was going to come. And so I always kind of pick through them to see what's interesting, and what seems more like, you know, what I just described, and your seemed really interesting. And I just thought this, this seems rooted in real science. It seems like science that's available to us now that we understand. And that's why I reached out, I guess, first, let me understand, you know, how did you Why did you go to college for what what were you thinking of doing when you were becoming a student?

Jeffrey R. Millman, PhD 7:18
Right, so I definitely didn't have diabetes research on my mind, when I went into college, even doing biomedical research was not a thought that had crossed my mind. My I went to the college and got a degree in chemical engineering, actually, I had, I came from a very poor and rural area in North Carolina that didn't have a very robust school system. And so I wasn't actually exposed to what, what that what biomedical research was little known what kind of biology was, and so I went into college thinking, I would just go and be an engineer, get a good paying job, you know, raise a family and all that sort of good stuff. And actually, during my time, as a undergraduate doing chemical engineering, I became more and more exposed to the overall biomedical sciences. And I thought, well, that's pretty interesting, you know, maybe going and doing work that is actually helping people's health is more interesting than going and working at a chemical plant to go and make the latest and greatest and shampoos, for example, or at a petroleum plant, which is pretty typical for a chemical engineer, as I went on, after my undergraduate work, to complete a PhD still in chemical engineering, but I sought out a laboratory that did some work with stem cells. And about halfway through my time during my PhD, mostly trying to catch up on the biology, kind of classroom training, but that I hadn't yet received during my undergraduate degree, I received a unique opportunity that my lab received funding from the jdrf, which is one of the largest supporters of diabetes research in the world. And that set me on the course that I've been on ever since. So they they awarded a grant to my lab that covered the last portion of my training during my PhD. And during that I got exposure to diabetes, the the needs that patients diabetes have in house themselves could be helpful for them. And so that prompted me after I got my PhD, that I was looking at all the options that I had after after that, and I was like, well, I really enjoy doing the research. But scientifically that the questions of how do you make a cell from a stem cell that can respond to sugar and secrete insulin? I thought that scientifically was very interesting. And I obviously didn't realize how major of a need that that was for a lot of people. Yeah. And so after that, I switched my trajectory completely to stem cell biology for for the context of coming up with a functional cure for diabetes. And that's led me to where I am today.

Scott Benner 10:34
That's cool. I want to ask you a question. I don't want to get too far off the path, though. But you went to MIT. So I was wondering how frustrating it was in high school, to not be in a terrific school system, is that something you felt as a kid, I

Jeffrey R. Millman, PhD 10:49
didn't really understand my situation until I was much older. If you're kind of born and raised in a certain area, you don't really know what you're missing out on. And I was fortunate in that for the last two years of my high school, I was able to get into this state wide magnet school program. So I was actually able to bless you with your high school, leave my school district and go as far as a high school that's actually part of the UNC system. And so I got to live on campus there for free and get advanced course work that I did not, I was not able to get during my, you know, pre High School and first two years of high school in my school district that I grew up in. And so that's really, you know, began to open my eyes to what the other possibilities were, though I didn't really get my head wrapped around by middle sciences. Until I got into college, I would say going to that Magnet School for high school was very important to be because I don't know if I would have been a fairly

Scott Benner 12:09
receptive to the new knowledge out there about you know, what biomedical research actually was, if I hadn't received a stronger foundation that the the second high school that I went to was able to afford me. So in hindsight is frustrating. But at the time I did it, it really realized what my situation does. It is really interesting, isn't it that you just don't know what you don't know. I'm, by the way, imagining your entire family that they must have Monday through Sunday t shirts that say my son went to MIT, my brother went to MIT, I would be wearing them constantly, I'd said to me, it's a very impressive thing. So you know, it's an it's amazing path to get from where you were to there and now doing this. So I wonder if you could tell me why stem cells are more interesting than other avenues for helping people with who can't make insulin.

Jeffrey R. Millman, PhD 13:04
I guess they were sorry, I'll start off by saying that there is a functional care for diabetes that is already out there. And that is cell replacement therapy, taking introducing cells that can be taking from a deceased donor, and transplanting them into a patient with Type One Diabetes. And it's not a perfect procedure. But in a lot of cases a patient will have can have reduced or eliminated the need for insulin injection, a lot of nuances there, I'm skipping over but that does exist. And this procedure is done probably about 100 times per year, more or less worldwide. And so I think that this is kind of unique in the cell therapy space of their being a kind of putting diabetes aside and thinking about it more generally, when it comes to cell therapy, what you would use themselves for this is pretty unique that there's already you know, very strong proof of concept that this can work. So why aren't Why isn't everybody receiving a cell therapy? Then and the very first challenge which I've dedicated the last 10 years or so, to overcoming is the problem of cell sourcing. I mentioned that the cells currently come from deceased donors and there just aren't that many deceased donors that are rounds and available for providing replacement, introducing cells for patients. It's kind of like if you ever watched these medical dramas like Chicago hope or Grey's Anatomy or you know or whatever, and you're like oh, we need to have a you know, replacement heart or liver or kidney in the next 24 or 48 hours. Are the patients going going to die and there isn't immediate organs available is that sort of thing, they just aren't that many donor organs available overall. Okay. Fortunately, for for diabetes, we have a therapy that is very effective and can, you know, maintain people's health for many decades, and that's insulin. But we still have this problem of self sourcing. And so when I was looking at options out there for what we would use, besides, besides the sea stoners, I felt that humans themselves for the most obvious choice that to make that occur. And the main reason for that is that the stem cells are capable of growing and dividing and making more of themselves virtually indefinitely. In my academic lab here, which we are not a, like a manufacturing facility, we don't make cells for going to people. So we're relatively small scale versus a company that would actually do this. But even in my in a relatively humble laboratory, we easily make several billions of cells every single week for our own studies here. And that would be enough for, you know, multiple people as as well. So having the ability to make a virtually unlimited number of cells as your starting material is a clear advantage. And most cells can't do that you can't just like take interesting cells in the body and grow them up indefinitely, they just like they just don't grow. So you'd have a stem cell to do that. The other advantage of these stem cells is that they essentially represent a cell type that is very early during embryonic development. And what that means is that we can, if we give them the correct signals, basically putting in like proteins, or sugars or chemicals into the, into the flask that we're keeping the cells, then we can direct them to transform from the sim cell into any cell found in the body. So you have a one mixture of proteins and chemicals, you can go and make heart cells, a different mixture will give you liver cells. And of course, the mixture that we care about quite a bit is, is producing cells in that particular cell type that produces insulin in the body is called the beta cell. So this is a unique feature that isn't really replicated by any of the other options there. And we've been quite successful with it, I believe, with our preclinical modeling in diabetic mice. Let me just interject here and make sure that people understand they're listening when you were talking about doing a transplant, that then infers that the patient needs anti rejection meds, is that right? Right. And that's still a pretty major problem. Right?

Scott Benner 18:02
Right. And so now you're basically treat change or excuse me exchanging Type One Diabetes for possibly cancer? Is that the concept of why that's not more widely considered? Do you think

Jeffrey R. Millman, PhD 18:14
so you need that you need a suppressant drugs can have a whole host of side effects. I'm not quite certain of cancer is one of them. Okay? Is there it's possible but the most obvious issues with that is that you're weakening a patient's immune system in order to make them so they don't reject the introducing cells that are be transplanted into them. So they'll be more susceptible to infection or sepsis, for example. Yeah. And that's maybe where it's a decimal as part of the reason as well, why there are only a few procedures done each year, because the people who are receiving these is facing cells from deceased donors, basically, the sickest of the sickest. They have severe hypoglycemic unawareness usually been hospitalized multiple times, because of that other organ failures to

Scott Benner 19:08
sorry, other organ failures as well, that sometimes

Jeffrey R. Millman, PhD 19:12
Yeah, severe complications. In addition to that, though, for though, I think one of the more scary things since what I've spoken to patients in the past, and you probably know better about this than I do is the is the issues of, you know, loss of eyesight, but also hyperglycemic awareness is fear that you might just go to sleep and not wake up. Yeah. And so, you know, these are these are particular, these are the sickest of the sick when it comes to patients type one diabetes. And so in that case, the negative side effects of immunosuppressant drugs outweighs the complications that they have from from their diabetes, right, right. However, that's obviously a calculus that boasts patient with type one diabetes. BDS can't accept, in most cases, the side effects of immunosuppressive drugs is not worth it in order to have better management of their diabetes. So this probably gets to maybe the third advantage of working with stem cells as a cell source here is the fact that we can genetically engineer these cells in order to make them better for transplantation. And kind of one of the newer areas that my lab has gotten into in recent in the recent year is to genetically engineer the cells so that you do not need to give the patient's immunosuppressant drugs anymore. That's basically change what signals the interesting cells are giving to the immune system to trick the immune system into thinking the cells are, should be there and are not from an actual donor.

Scott Benner 20:59
That's that's magic. Jeff, that's, that's absolutely amazing to hear it really, it's, it's astonishing to hear someone say that I tell the cell to give off a signal that makes the immune I mean, that's crazy, man, like, You're brilliant. How did you? Thank God, you're not making shampoo? Although I bet my hair would be amazing.

Jeffrey R. Millman, PhD 21:20
Yeah, your hair probably be great. Maybe some stem cells can help you out with that. No, I and the analogy I get here is that, you know, the sentences I just said, you know, a few years ago were like, legitimate science fiction. Being able to do this, in a like a realistic way was simply not possible even a few years ago, it was an idea people had. But the theology wasn't there, both on the stem cell technology side, but also the genetic engineering side, in order to be able to do that at all meaningfully. And only really, in the last, I would say, year or so half both the genetic engineering capabilities and the stem cell technology doesn't the point that we realized that we can do this now it's no longer, you know, five years ago is definitely science fiction of like, oh, that'd be nice to do. But a year ago, we realized that, oh, we can do this now. And you know, overcome one of the major challenges of a cell therapy for patients with diabetes. So this may be one of the fun aspects of my job here, as a faculty member, is that, you know, we get we had the flexibility to, you know, start pushing the envelope and going beyond a transforming things that are science fiction into something that's reality, and hopefully, eventually a therapy that can help the millions of people that could benefit from it.

Scott Benner 22:56
And tell me how you go about testing this? It's, it's on lab mice, is that correct?

Jeffrey R. Millman, PhD 23:02
Right. So the test out how effective ourselves are in terms of as a potential therapy, we take lab mice, we give them a compound that is able to destroy the mouse's own introducing cells, we get the mice diabetes, by you know, basically killing off their their own cells, and then we do a transplantation into these mice at the sea, you know, are we able to first reverse diabetes in these mice? Can we do it rapidly? And the second question is, how long are we able to keep that diabetes care? And number three, are there any ill effects of the transplants? Do they one of the fears is the potential of the cells we're putting into the mice to perhaps become a tumor? And so we go and we look for any signs of tumor formation, or you know, any other sort of, like biochemical changes in the blood chemistry of the balance that would be indicative of major health problems. And it really only this year, with our recent scientific applications, have we been able to answer positively to all those questions, and with heinously, the cells that we have now are able to virtually instantaneously reverse diabetes in these mice. It takes about a week or so because we have blood the blood vessels grow into the cells we're putting into the mice, but after that, the diabetes has been reverse diabetes reversal last for the lifetime of the mice, which is about a year and then there has been no signs of any health problems associated with the transplant the blood chemistry looks Good. And the there's no signs of tumor formation. And we've done this a lot of times. Now I think the total number of mice that we have transplanted with our latest version of the technology is over 100. And so far, we have a 100% success rate when it comes to curing diabetes, and a 100% safety rating when it comes to mice we have transmitted,

Scott Benner 25:28
what's the next step after a mouse? Unless, by the way, Jeff, and I'm just thinking out loud here? What if you found a way to turn a person with diabetes into a mouse and then gave them stem cells, then turn them back into a person? I think really that maybe is what you should be looking into. But just in case, that's not possible, what do you do after you've proven it out over and over again, in a laptop mouse? Do you move on to a larger animal something that's more closely related to people? I don't know, what's the process?

Jeffrey R. Millman, PhD 25:57
Well, I think also, we have to keep in mind how important the diabetic mouse community is to us. And maybe they should be the priority first. I'm just kidding, of course. So, actually, you asked a very hard question. And it's actually been in a lot of discussions, and there have been a lot of people who are, you know, experts in the field that give very different answers to the the question that you just just proposed, there are, there's an argument to be made, that having great success with a mouse model of diabetes is sufficient, and that we shouldn't waste any more time trying to make larger animals work with the technology instead should just go straight into a phase one clinical trial, I think it's a lot of merits to that. There's also an argument to be made, that a large animal like a nonhuman primate or a pig has a physiology that is more similar to a person than what a mouse is. And that showing pre clinical success. And one of those models is a necessary stepping stone, when it comes from going to where we're at right now with great care rates in mice before we put it into a person. And so I I personally am kind of stuck between these two positions. And I think a lot of it depends on sort of your,

on your

what you're trying to get out of this, I think as maybe a if I put on my academic hat, I think it's a lot of value. For going into the larger animal models, we can do a lot more testing and a lot more invasive work. When it comes to large animals. And I apologize for the siren in the background. I'm actually at the medical school that you

Scott Benner 28:19
might get, you might get more work done if you moved out of that firehouse, I think

Jeffrey R. Millman, PhD 28:26
well, the Dalmatians are very nice to keep about lab morale, you can give them

Unknown Speaker 28:31
diabetes and see if you can.

Scott Benner 28:34
Well, you're in between you're not I'm in between what what stops? So is it biases is that people who are just like, Look, I want to move on this, I think it works or is there real, scientific reasoning for both of the ideas? Maybe we should try another animal larger? Maybe we should jump to a person like what are the arguments for each Do You Have you heard them? So the

Jeffrey R. Millman, PhD 28:57
arguments for going into a person is that there is that mice are as good as a large animal in terms of guaranteeing the safety of a person. In fact, there's already when he made that mice are better safety model. For them what a pig or a non human primate is, because of some of the special genetic mice that we have. They allow for health issues to be easier to detect than what you would see inside of a large animal. So the argument for going to people would be that mice are as good if not better than then barge animals to ensure safety of a person. And so if we already have all the data, proving the safety of the product before going into a person, we might as well go into a person to you know number one, help to accelerate transition to translation of this over to a, a care. And number two, the the effectiveness of the treatment in a person is going to be more meaningful than the effectiveness of a treatment in any animal model. Because obviously, we care about how it works in a person a lot more than we care about a monkey or a pig, or a mouse or a Dalmatian. So that's the argument for doing it. The argument for doing it in a large animal is that we can you know, do, we don't have to go through as much regulatory hurdles, basically, to go and get answers in terms of effectiveness inside once transplanted into a large animal model. There isn't a you know, FDA? Well, at the clinical trials when it comes to large animals or regulations for it, we can't go about it, willy nilly. And there's ethics to consider. But those you know, those are similar to what we already do with with the mice. And so we'd be able to, if we decided to do large animal work today, we would probably be able to in Sydney, we didn't have the program going right now, we would be able to realistically do this in probably two or three months, as opposed to if we decided we wanted to go into a person today, assuming the FDA didn't require the large animal intermediate. I don't know the answer to that. Right now. It would probably take two years to go into a person.

Scott Benner 31:38
Well, I have questions around this. Because I'm always fascinated that as people we see things as either or it's always one or the other. Why not? Both? Why not move forward on both of them at the same time? And then abandon the one that that doesn't end up being needed? Like, and and are there any? I don't know what the word I'm looking for is, but does the FDA ever make allowances for people in situations that are dire? And Couldn't you find a person in their 60s has had Type One Diabetes their whole life? Who is really at the end of their health rope and just say this is this is reasonable to try with them? Do you know what I mean? Like, when does common sense? jump into this?

Jeffrey R. Millman, PhD 32:21
Right, and I think the way you phrased the question at the beginning, it kind of matches what I the way that I do this is at the flexibility of being a academic working in the space, that I try to do what I can in order to, you know, in terms of developing new technologies, and giving advice to people to help companies go into clinical trials as fast as possible. But in the meantime, we do our own academic research here. And I'm not doing academic research on people. And so we have already done some large animal transplantations as part of our academic mission here. So essentially, kind of terms of like me personally, when it comes to being in the field. You know, I'm kind of able to play both sides, if you will, without having a academic program that uses large animal models of diabetes, while also trying to help companies that may be wanting to bypass that and go into a clinical trial. However, when it comes to, you know, an individual company's perspective, and I don't want to I'm not speaking for anybody in particular, but just kind of thinking about the types of questions a company would want to ask themselves, they would need to make a decision on you know, if, you know, they want to, you know, spend finite resources on a large animal models or on clinical trials are trying to split it across both and they may face the reality that they don't have the resources to, both and you know, may need to go and choose one over the other. So that that's maybe the argument for not doing everything is if you don't have the finances to do it, or the ability to do it, you got to go down the only option that you have available to you. So you made reference to kind of a an emergency clearance type of decree, I don't know what the exact terminology is for it's from from the FDA. And this is it's been happening a lot when it comes to like COVID-19 testing. I know a lot of these diagnostic kits I've been receiving like emergency clearance from the FDA, since we're in the middle of a global pandemic that is killing hundreds of thousands of people this year alone in diabetes, for the most part doesn't really fit in terms of

terms of that there being a good pill parallel there.

Overall, the FDA again, as I as I understand it, I'm not I don't represent the FDA or anything, but as I understand it, the, you know, FDA is wanting to balance risk here. And if you have a new therapy that you're wanting to do a trial for get a vergence, the approval for what is the alternative there? What's the relative risk and reward there. And since

diabetes is,

you know, that is controlled to at least a certain degree by insulin or insulin sensitizers. The oftentimes there isn't a, I could imagine the FDA looking at that and thinking that's there is not a justification for a kind of an emergency clearance or emergency clinical trials, when it comes to a cell therapy. With that said, there's gonna be maybe some sub populations of patients for which that could be an argument for I could imagine I'm just kind of spitballing here a little bit, but there are kind of going outside of type one diabetes, there are certainly certain rare genetic forms of diabetes, the so called like Modi's or neonatal diabetes, or Wolfram syndrome, or cystic fibrosis and do cbds, that maybe some of those cases could fall into that that'd be one possibility going forward with it. But it just that some,

Scott Benner 36:33
somewhere the imperative lies that it's worth the risk and taking the leap. And by the way, like, I'm obviously not a historian on this, but don't most of our major advancements fit into a mold like that, like just something that had to be done. And we did it and it works. So we kept going.

Jeffrey R. Millman, PhD 36:51
Yeah, I'm no medical historian. Well, I don't know if I can really

Scott Benner 36:55
yeah, think about, it just makes sense. Listen, maybe I'm writing science fiction, too. But it just makes sense that, you know, there's somebody out there who's in a dire enough situation that be like, Hey, give me the mouse thing. And let me see what happens. And if it doesn't go, Well, it doesn't go well. But I didn't have much to lose to begin with. And, you know, he just would think that was I don't know, Jeff, maybe we left prisoners with type one out for doing that, you know, there's got to be a way is what I'm saying. There's got to be somebody who would be willing to like make take the risk, because the risk would be reasonable for them.

Jeffrey R. Millman, PhD 37:27
Oh, you mentioned the prisoner thing. I don't know if you're aware of medical care. And but I do know a little bit when it comes to prisoners, when it comes to what we call human subjects research, there's actually been a bit of an issue in the past in this country, on kind of compelling prisoners to engage in human subjects. Research, I don't know that it's the proper clinical trials. But there's actually a lot of it becomes the issue of like, having the ability to properly consents to things. And if you're a prisoner, and do prayer, given you're kind of maybe can feel compelled to do things that are against your self interest, because of the imbalanced power dynamic. So actually, if you want to do any research with human subjects, and you want to do it with prisoners, there's actually a lot of additional regulations involved in doing that. Because of the inherent, disproportionate power dynamic that occurs when you're dealing with a prisoner, to the point that I don't think there actually is much work at any done with prisoners. Because of what's happened in the past.

Scott Benner 38:49
It's, it's funny, I was just reaching in my mind for someone who would be in a dire enough situation, like I wasn't saying to, like knock three months off of a larceny run, I was talking, you know, I was talking more about like, I'm gonna spend my life in prison, maybe I would take a risk with that life to to get it out. And meanwhile, I completely understand what you just said, and all the other parts of that, that seem untenable. I really, I could have just as easily reached for any other, you know, example out of my head, I wasn't like, you know, we have those prisoners, we should use them. That's not what I was.

Jeffrey R. Millman, PhD 39:23
But I think I'm glad you brought it up, though, because I I spent a lot of time speaking to audiences of patients with that diabetes in their families. And I know that there is a frustration that exists when it comes to the perceived slow pace of scientific discovery. And that actually being translated into a into an actual therapy that been themselves or a loved one, and oftentimes gets very direct questions about like, why is this true? Like you can already do amazing stuff with mice? Like, why aren't we just putting it into people right now as a very reasonable question. And the frustration behind the question, I think is very reasonable. But I think the like the prisoner thing is an example of the types of considerations so we have want to keep in mind that the path from a having very good preclinical animal model evidence of a new treatment, or functional care for for diabetes, is just the beginning. And to go from where we are at right now, academic research into a therapy that can benefit yourself or a loved one, loved one is a long path that has to be treated very, very carefully. You know, the prisoner thing kind of illustrates one of the ethical dilemmas that could occur, you know, issues of, you know, the large animal model that we talked about several minutes ago is another one as well, like, is that required or not, and people who are experts in the field, you know, disagree on that, on that one issue. So I think all the points we've been bringing up here, I think, very clearly illustrates that it's not a straight in easy and direct line going from where we are to where you want to be that there is, you know, a lot of care that needs to be taken in order to do this correctly. Otherwise, we're going to end up, you know, taking even longer to translate this care to help people in the long term, and, you know, could potentially hurt some people along the way, we're not very careful in how we're doing this. And we, we don't want to, we don't want for that to to occur. And to give you maybe an example of that, this is pretty, pretty another again, I'm not a medical historian, but I do know a little bit of things that are becoming more famous kind of a case studies that are out there. So in the 90s, there was a lot of hope and hype for gene therapy to care, a lot of diseases, we were getting better at genetic engineering technologies at the time. Of course, now we're a lot better. But the 90s is really where a lot of the stuff started to happen. Instead, there was a clinical trial started to do gene therapy for children with a severe genetic, immune deficiency that you may have heard, like bubble boy type of terminology, these people have mutations, a mutation that basically gives them little to no immune system. So there's clinical trials that happen in the late 90s, in order to in order to treat these patients, and one of the patients, a young boy actually died from the treatments. And so what happens is a bit that's very unfortunate, very tragic. And what happened to the field is that basically, all work with clinical trials with gene therapy stops, and nobody was willing to pursue gene therapy for people for about two decades, and only now have things kind of warmed up to begin doing this again. And fortunately, it seems to be a lot of people are treading a lot more carefully. And are and are, you know, doing a lot better. Again, the technology is approved a whole lot and gene therapy, the way we do it now is a light year ahead of where things were in the 90s. Right. So and so so i think is a cautionary tale that if we do this wrong, we can end up you know, hurting people and then delaying progress to a cure potentially for decades. Because Because the academia side will run away from it, because it's like, it's scary, and it went wrong. And you don't want to be attached to it at that correct. Yeah,

Scott Benner 44:24
I say so there's that human so it's just a myriad of things to consider. And some of them have the potential to significantly waylay progress. And and so you want to be careful moving forward and do it in a meaningful way. I you know, I don't listen, I'm not a person who thinks that you've got the answer over there on your desk and you're just not giving it to us. I don't have that feeling but a lot of people do get that idea of like, well, there's more money in the treatment that there isn't a you know, in this but this is not a cure either. This would be you know, this would be a treatment that would go on you don't honestly know it. You would need more cells, as a human life move forward at this point. So

Jeffrey R. Millman, PhD 45:05
yeah, the timing issue is one of the big scientific questions right now. And the city where the large animals actually have a benefit here, that we are limited by the lifespan of the mice that we're using currently, in our studies, and that's about a year. And so we know for for a year for the lifetime of the mice, the cells seem to function perfectly fine until the mouse is dies due to old age. And so we don't know if that means that at like, one year, one day in a person, all of a sudden, the, the transplant doesn't work anymore. And then the patient wouldn't need a dosing, or if those are going to last for years and years and years or decades, or for the lifetime of the actual patient. Right. It's but I do think that even kind of in the worst case scenario here, if the cells end up, only working for a year or so, which I just intuitively, I think that's not going to be the case. But as soon as That's true. I suspect that many people would choose a dosage of cells every year or so over what they have to do every single day. Again, I'm not I'm coming from this from an outsider's perspective, I am not diabetic, and I don't have any family members who are diabetic as well. But I spent a lot of time because like, it's very important to, you know, keep the eye on the prize here. So I spend a lot of time speaking with patients understand their stories and their motivations there. So that I had that in mind while I'm conducting my academic research here. And from from like, from, from my discussions with everybody, and to get out of you know, this a lot better than I do. That I think that most people would accept a once a year treatment over what they have to do right now.

Scott Benner 47:05
Well, yeah, I think for my daughter, I would definitely want that. And I believe she would do as I'm speaking for, but and what are we talking about? Do you do know how we're talking about the implantation? Is it just a large needle? Like thing? How do you How would you get the cells where they need to go?

Jeffrey R. Millman, PhD 47:22
I, I guess how?

Unknown Speaker 47:24
Much another question. Yeah,

Jeffrey R. Millman, PhD 47:27
yeah. So the way we currently do it in mice is not the way that we would do it in people. One of the problems with with my side, everything is anybody. And we don't necessarily have like cutting edge. microsurgery equipment in my lab literally is like me sitting there with a mice. So to do surgeries for my lab, like the only real thing that I'd be as the director of the lab, I feel to actually do in the lab. But you know, it's literally me over a mouse, putting themselves into the mouse. And so we actually currently in the mice, transplant them into the kidney. Because for practical reasons, not for translation reason, okay. But for for people, we would need to figure out the best location to do this. And the complication there is, is basically the amount of blood that is available. One of the great things about producing cells is that they don't actually need to be in the pancreas or native Oregon, in order to do their job. If they have enough blood flow, they're able to sense the sugar levels and the blood and deliver insulin into the bloodstream. So that's the only real requirement there. But not every area in your body has the same amount of blood available for the institute's themselves do their job. And so a lot of people are hoping just to be able to put the cells just underneath the skin, or maybe into a muscle so they could have a needle injection type of thing. And that's looking promising. Now, it's kind of hard to do that, just with like naked cells into the into the spaces because of the relatively low density of blood vessels there. But if a lot of work done with various types of biomaterials that can help to promote an increase in blood vessel formation there in order to enable so you basically kind of created like a little pockets underneath your skin or in your muscle that is supportive of the introducing cells to do their job by providing them with enough enough insulin. Alternatively, you could put them into a different organ. People don't want to do it in the kidney because of a lot of people with diabetes, having kidney issues. So what's actually done clinically right now is to inject them into the liver. So that is highly vaster alized as an Oregon, and also most of the work that insulin does, and your body actually occurs in the liver, and so having the instantly delivered directly into the liver is good. From a physiology perspective.

Scott Benner 50:24
That's really incredibly interesting. I'm having a lot of fun talking to you about stuff that I thought I wasn't gonna understand. But I am understanding I, I, I want you to know that over the years, I have many opportunities to talk to people who are in similar positions to yours, but I never felt like what they were doing had a real chance. And and you talked earlier about how things have sped up so much recently, I just wondered if we could detour for a half a second. What made that leap? Is it? Is it like the advent of supercomputers? Are there like how did you how did we speed up like this,

Jeffrey R. Millman, PhD 50:58
I wish we could figure this out with supercomputers, because that'd probably be a lot less work and less pipetting on my teams. And in order to do this. So really, the watershed moment here, occur occurred, actually, before I became a faculty member here at washu. So after I got my PhD from MIT, I, and I decided I wanted to do diabetes research, I actually did a what's called a postdoctoral fellowship, which is basically your time between getting your PhD and becoming a faculty member. So I did that down the streets, from MIT at Harvard University, in a famous diabetes lab over over there. And so the test that I had during that period of time was to figure out how to make these cells basically, when I started doing my fellowship, I, the field didn't actually know how to produce these cells at all, we knew how to make progenitor cells. So these are cells that were kind of halfway between a stem cell and a introducing cell. But we didn't know actually the correct proteins and chemicals to, to put into our flask in order to make them go all the way into a insulin producing cells if people had tried to do what you just suggested with supercomputers or that kind of kind of computational methods in order to do that. And the truth of the matter is, we don't understand biology enough, in order for these, what we call in silico methods to be able to be very productive predictive of approaches to making it so I was tasked with basically trying to figure out how to get over this problem that have existed for the 20 years that themselves had been since since those had been invented 20 years prior to this. And we hadn't been able to figure out how to make these cells during that time period. So essentially, the trick was to read a lot of papers that were describing how this occurs, naturally in embryos. So this is mostly like, how do you get cells and fruit flies or fish or mice. And so those are the, what we call model organisms that we use to try to understand how a embryo develops, develops naturally, to go and look at what lessons people had learned from studying these animals, and then trying to translate them over to our humans stemcell bioreactor context. And so I literally went through I did, I did a estimation after the fact there was about a 180 papers, and found that only about two or three of the

papers actually

provided chemicals and proteins that we could put onto ourselves cells in order to actually make them basically it was a matter of going through the literature, finding papers that were irrelevant to actually making the cells in our artificial lab ground context, and find the few that were actually relevant and to kind of make these what to call first generation cells. So we're able to take these few papers, figure out the compounds from it, and be the first to make introducing cells that were capable of controlling diabetes in mice. And once we were able to do that with them, first of all possible with existing technology, and do some of the Pacific compounds for how to do that. It became a question of being the first To do it to taking these cells that were very immature still, but were definitely the correct cell types that we wanted to make there and optimize. And so that's optimization is taking something and making it better, is infinitely easier than going from nothing to being the first to create something. Yeah. So it's really the watershed moment that we went from not being able to do this for 20 years, to then, over the course of then figuring out how to do the first iteration of this, and then go for the next five years after that into a improved sell product that is now able to reverse diabetes and be safe. And all these great things that we talked about earlier. I want to understand the

Scott Benner 55:47
timeline, you reading that literature and coming to that, that idea. How long ago was that?

Jeffrey R. Millman, PhD 55:54
So I started in 2011, doing this, and we pretty much had figured it out by 2013. And we published the scientific reports on that in 2014.

Scott Benner 56:11
And one day, well, this becomes a thing we're gonna call it the milman method, is that correct? We're gonna get your name, right.

Jeffrey R. Millman, PhD 56:16
Well, there's a reason I keep on using the word we and that seems to Team science, right? It's like, nowadays, science is so big and so hard that it is really difficult for a individual to be the one to to come up with something that's truly transformative, that moves the field forward and not impossible. But more often than not, you are better off working with, with grapes. And now of course, I lead a team of 10 scientists here at Wash U. And so everything that I'm involved in, but obviously involves other people on my team, and oftentimes other people at other institutions as well. And so I really think that team science is the way to go forward here, because it's not going to be one person. If this is a problem, that is too important to expect a individual person to solve, we all need to be working together. In order to do this. And everybody that I work with on this all shared the same vision that we're all in this together for the greater good of coming up with a therapy.

Scott Benner 57:30
And we're seeing this with COVID. Right now, too, right? Aren't labs sharing information at a, just an unprecedented rate now around COVID?

Jeffrey R. Millman, PhD 57:40
Yeah, it's something that I have never seen, to that extent before in my professional career, that, you know, we have these groups that, you know, we're never working together, all of a sudden started to work together to solve this very important problem of how to deal with COVID-19. And it's complications. And I think part of this as well is kind of where we're at now, in terms of the ease of communication and the ease of disseminating information. There's a lot of me, this has been a lot because of how much the Internet has advanced even in the last 10 years. But in particular, it's become kind of a trend in the last maybe three years or so it's on my radar. I know it existed before. This is what we call preprint servers. So normally, when you publish a scientific article, you write it up, you have to be submitted to a journal. And then there's an editor assigned to it editor goes through it to kind of make sure it's not completely wacko. And then it goes through a process called peer review, where sent out to usually three other scientists in your field, your peers, and they go and they critique it. And they recommend that it's either published as this has to be revised or is rejected. And this is a process that maybe on average, can take between six months and eight months. But it's not uncommon for it to take over a year before it's actually published and out there for the scientific field to go and benefit from. However, there have been what are called preprint servers that have been developed where before you submit it to peer review, like a discus, you'll do an additional step before that you submit the article to a preprint server, it still gets a quick look over from an editor to make sure that it's not something you know, crazy or inappropriate. But then within 24 hours of being submitted, it is online and available for everybody to look at again, it's not peer reviewed yet as this disclaimer forth, but these preprint servers have been amazing. In order to not have this six month, eight month, one year lag, and information being disseminated, and the information is out in 24 hours after being submitted, and obviously, that's very important when you're facing a immediate healthcare crisis of a, a pandemic.

Scott Benner 1:00:20
Do you think that generationally that that researchers have moved along with society thinking, bigger picture? Do you see that as well? Because I mean, listen, if I was going to cure something, I can see, I'm 50 years old, I can see me thinking, I want my name on this, I want people to know, I cured this, I can also see how when we get to COVID, everyone in the lab all over the country in the world are starting to think well, Hell, I could get this too. So I guess maybe we ought to get to work on this. And, you know, like, I could see that kind of breaking the levee have been maybe not caring so much about who gets the credit, but more caring that there's a way to treat. And, and I do but I do wonder like, I look at the like my son's 20, he doesn't have type one. But you know, I look at his generation. And I listen to hear him speak with friends. And it all just feels a little more inclusive when they're talking. And I do wonder, too, if that isn't a little bit of maybe credits, not the most important thing, although, you know, I mean, you know what I'm saying? Like, I'm wondering if things aren't just shifting in general, but what you said about the internet and communication improving is huge. I don't think people think of the internet as, as all that it really is, you know, I think they think of it as making the Xbox work or, you know, being able to send an email. But but it's really fascinating. Jeff, I'm thrilled you came on. Can Oh, let me ask you the question. First, do you think that there's a the community, the scientific communities moving along with maybe the social world,

Jeffrey R. Millman, PhD 1:01:49
I think there's definitely parallels there. And I definitely would say overall, younger and newer faculty tend to use the, like the preprint servers and the early rapid dissemination of information more than senior investigators, I'm not certain how much of that is kind of a different inherent kind of technological aptitudes of younger people and older people overall. Or, you know, if there's the the mentality when it comes to the credits, but but I guess that is an important thing to acknowledge that one of the things that scientists like myself have to balance is that, you know, we all come into it with kind of ultra altruistic views of wanting to benefit. No people, in this case, you know, people with with diabetes is something very, very important to me. So we come up with all sorts of views. But there is a kind of a reality that a scientist needs the face of, you know, being able to have a career and maintain a laboratory, we, you know, we all have to compete, because it all comes down to money, essentially, but not like not like money that we're taking home, to an editor in our bank accounts, but like money in order to actually do the work all scientists, diabetes researchers and all the researchers, we're all competing for a finite amount of research funding that is out there. And thankfully, we have foundation support from you know, jdrf, and American Diabetes Association to allow for them to be more money, focus on diabetes, then there would be otherwise we're just relying on federal money like the, from the National Institutes of Health, but then it is all still finite. And in the end, you still have to as a scientist, you know, compete for these grants and publish papers of sufficient renown. In order to motivate a foundation or government agency to give you the funding, there is a balance that we have to strike, because we want to do good. But we also need to ensure that we are competitive for the money in order in order for us to do the good that we are, you know, striving to accomplish. So when I talk to my trainees in my laboratory about this, I oftentimes will purposely point out that I am thinking about the discussion one way or another, I'm like, okay, we're thinking about we're talking about this right now, in terms of what is the best stuff we can be doing in order to lessen human suffering or improve patient health? And then or switch be like, Okay, well, this is the stuff we need to do in order to ensure that we have funding for the next five years, and the way we approach questions or the steps we might take can be different depending on what is kind of the immediate concern there. If only and we as scientists have to balance all of this, and it's a juggling act, that different scientists perhaps have different durations will come to different answers to? Well,

Scott Benner 1:05:16
I'll tell you what you just said, it's not lost on me at all. Because this podcast, I know, you don't know it, but this podcast helps people. A lot of people understand how to manage their insulin, which brings their time and range, tighter brings their agencies down and gives them better health outcomes. And it's a full time job making this podcast so I take ads on the podcast, and there are some people who think you shouldn't take ads, but to them, I would say, if I didn't have an ad, then I'd have a different job and you wouldn't have this podcast. So you know, at some point, you have to, you know, you have to you got to you got to eat right, you're not you're not rolling around St. Louis in a Lambo. I don't imagine Jeff, right. When you say, when you say you need that money, you need it for equipment, lab space, materials and quality people, right? Like I imagined someone who knows what they're doing cost more than someone who doesn't know what they're doing.

Jeffrey R. Millman, PhD 1:06:08
Right. And it doesn't get good, good, maybe a good distinction to make fair like when like when by my lab gets a research grant from jdrf, or ADA or NIH or whatever, I personally don't get like a raise or anything like I don't take home, I have a salary, I have a set salary. And that set salary is there, no matter if I am doing a good job in terms of curing diabetes, or doing a bad job when it comes to curing diabetes. Or if I bring in big grants or I'm not begging and break the big grants, the amount of money I take home is the same. So I actually don't receive any of the money personally, but you're right, the money, the money all goes to supplies and equipment and the salaries in order to hire people or to train people in my lab in my laboratory. And that's very important as well, that part of my mission here is not just to be you know, coming up with a functional cure for diabetes, but also to be training the next generation of scientists and so I have undergraduate researchers come to my lab and some of them need have financial aid requirements in order to be attending watched in the first place and so I have to pay a portion of that in order to have them have the privilege of being able to do Diabetes Research. Same thing with a PhD students, I have to pay their siphon and their tuition, and also postdoctoral fellows as well. And these are all people that I'm training that are doing the work but I'm hoping are going to be trained to then you know, go on and either companies or in their own academic labs to continue the fight for a cure for diabetes and they but they but they need to if they don't get a salary to be able to do it then they're going to go and do other things like not a big purchase or go work on a different disease area and I'm rather than work on diabetes with me then go and you know, make shampoo at Johnson and Johnson but like I was thinking about doing for a while or you know, go and work on a different disease area, no offense to that disease areas, but my focus is diabetes and so I'm going to compete in order to do the best I can in terms of research and in terms of training in order to advance that as much as possible.

Scott Benner 1:08:36
That really speaks to me what you said honestly, you need quality people who who want to do it and I loved your answer because I want people to hear that I honestly want people to know that you're listening in my estimation, you're a brilliant guy who could be doing other things you could be rolling around a lab working on conditioner, wearing $200 shoes and driving a you know a fat car and and living a completely different life but you're putting your ability to think through these ideas into something as important as diabetes and and I appreciate that I hope other people do as well. I have a couple of quick questions. And I'll let you out here. I know we're over time a little bit different does this have any application what you're working on to type to

Jeffrey R. Millman, PhD 1:09:18
get at the type two situation is a little bit more complicated than type one. But the short answer is yes. The type two type population is more heterogeneous and there are definitely many people maybe even most people with type two diabetes that probably wouldn't benefit from from this because their diabetes is already managed sufficiently with diet and exercise and or with these other you know, drugs like the instances of Tyson drugs. However, I think that in my discussion with endocrinologist backs us up as Well, that's the more severe type two diabetic patients, the ones who are taking insulin like patients Type One Diabetes do as well, they would be able to benefit from it, since you could think about these cells as essentially a insulin production source. And the patients need insulin, then it could become from the cells and set up in the insulin injection, the complication there, which makes it a little bit maybe a little bit more challenging than in the Type One Diabetes case is that most patients with type two diabetes have what's called insulin resistance. And so they per kilogram of or pound the body weights, they require a larger dose of insulin in order to maintain normal blood sugar levels. And so what that would translate over to is that you would be the transplant even more cells into a typical patient with type two diabetes than the typical patient with Type One Diabetes. But that is a hurdle that could be overcome, again, because of the positive features of stem cells in terms of being a self renewing cell source that, you know, we can go and make a few billion cells for them, as opposed to baby 1 billion cells that a patient with Type One Diabetes would need.

Scott Benner 1:11:25
Okay, I see. All right. My last two questions are this one seems kind of outlandish, but are there like you taught a cell how to sense glucose and make insulin? What else could you teach it to do? can it make me taller? Or like what else? Like, you know, I'm saying like, Where's this headed?

Jeffrey R. Millman, PhD 1:11:44
So I guess the way to think about it is that we are only teaching the cells, what evolution already taught the cells, basically, we're not telling them to do anything that is artificial. All we're doing is trying to give them the signals, they would normally get in the developing embryo that would tell them to become a beta cell or is producing cell, all we're doing is trying to copy that inside of the laboratory. So evolution already figured all this stuff out for us. And all we're doing is trying to copy evolutions work in the laboratory. So that means that we have so we do some sort of exotic genetic engineering tricks just possible, I guess, but at least with how we're making the interesting cells, that means that we can't tell the cells instruct the cells to do anything that they wouldn't naturally be able to do in the body. But with that said, I mean, maybe he gives them a growth hormone artificially to go and make you grow taller, and produce insulin, but you're probably better off not doing that. Yeah, I was hoping you could

Scott Benner 1:13:05
fix my plantar fasciitis actually, or, or I could dunk one or the other. I wasn't sure what I was going for exactly there. But I just wanted to understand, you know it. And that's a really great explanation of it, that you can just do what what nature knows how to do, that's, that's really is probably comforting, to be perfectly honest.

Jeffrey R. Millman, PhD 1:13:26
My, my professional advice for you would be to just get the shoes with like platform shoes, or like, get a springboard in order to go and probably to be much more economical for you, then try to use a cell therapy for it. Well,

Scott Benner 1:13:40
Jeff, I was gonna tell you, you could come back on the show whenever you want it if I could jump higher, but now you're making me rethink my offer. Well, so two things. And so I don't forget to say it whenever you were terrific. And I really enjoyed this. So if you ever have anything else you want to say, carpenter, you just let me know. And I guess my last question is then timelines like, what are your What are your hopes for this?

Unknown Speaker 1:14:07
Yeah, I

Jeffrey R. Millman, PhD 1:14:10
you can imagine I dislike the timeline question because, of course, should I be held anything but also because it's very difficult to predict timelines when it comes to any clinical work little than kind of a major novel clinical treatments, like a cell replacement therapy for for diabetes. I am hopeful that in the next few years, we there would be clinical trials that are like could be initiated, and we have been in discussions with a lot of partners in order to make that happen. And that does seem to be very realistic. So I feel pretty good about in the next few years clinical trials could begin. However, I think the bigger question which is a lot harder to answer is, when is this going to be a widespread treatment that the average person with diabetes could have made available for them? And that's simply impossible to know the answer to I've been doing this a long time, I'm not naive enough to ask you that question.

Scott Benner 1:15:31
I was just wondering what you were hoping your next steps were? So what what gets you to those clinical trials? Is it money?

Jeffrey R. Millman, PhD 1:15:37
Money? Yeah, it comes down to money. And that's both in terms of, you know, advancing our technology, but also just doing the necessary steps to translate our kind of, we want to call it a research grade process into an actual clinical grade process, it all comes down to dollars and cents, is it

better? It's,

Scott Benner 1:15:58
I'm sorry, Is this better off in academia? Or would it be better off privatized? What if somebody came along and bought it with this fear be then that they might not follow through the same way, and they'd want to bastardize it for something else? Or, like what gets it done more quickly?

Jeffrey R. Millman, PhD 1:16:13
I think that there are viable paths with either direction. And kind of the fear that you mentioned, when it came to kind of a company involvement, that there are protections that can be put into place to make sure that a company doesn't like swoop up the patents, and then sits on them to prevent a care from actually helping people, Jeff,

Scott Benner 1:16:39
is that I don't mean to cut you off. But is that light bulb story true? You ever heard that, that 100 years ago, a guy designed a light bulb that would never burn out and a light bulb company called him in, bought his patent from him burned everything he brought and broke all the light bulbs right in front of him? Have you ever heard that?

Jeffrey R. Millman, PhD 1:16:56
I have heard that I have no idea if this actually true or not. But I think we I think the the people who manage, like technology portfolios are a lot more savvy than they are 100 years ago. And I guess one of the aspects that we haven't talked about when it comes to to my research here is that in addition to the the core technical team that we have here, Washington University, also has an extensive technology management office here. And their job is to worry about these sorts of things to make sure because obviously, I'm not a patent attorney or lawyer to give me the file past inventions or to figure out licensing deals with, with companies or other entities, I don't know how to do that stuff. It's so washu. And it's pretty true for other major research universities as well have a office that is dedicated to that, in order to protect the interest of the university, but also the interest of the technology. And so this kind of relates to the protections that are put into place to make sure that somebody doesn't go and buy the patent for your light bulb and then destroy everything and make it so it's not available for people you can write, you write in into these contracts, essentially, that the person who license or buys the path that has to proceed with commercialization. And there are very strict deliverables that a licensee has to do in order to continue having the rights the patent, if they do what you said, which is the sit on the patents, then they're in violation of the agreement, and the path that reverts back to Wash U. And in this case, to or the university, whoever holds that the patent rights are originally and then we're able to go and you know, find a partner who was not going to play these, these silly games. Yeah, I guess it's possible, but there are ways of protecting yourself and also protecting the interests of patients. And so this idea that that companies are out there and would never allow for never allow for a cure for diabetes to come. Because they make so much money off of insulin just isn't true there. There isn't any real basis in reality for it. And in fact, I would say that, overall, the companies that that I'm aware of in the space, all view this as being the future and all have at least a small internal program and not a large program to make sure they end up not following The the lesson of like a Kodak, for example, who were the ones who discovered digital photography, and they just decided not to pursue it because their film industry, business was making so much money. But then other people develop digital photography, and Kodak get left in the dust because there's a Kodak and Polaroid Sorry, I forget which one, right, but the film one. So I think that's actually probably the the more relevant analogy here than the than the lightbulb analogy that these companies make money from from insulin and that's true, and you're gonna get arguments that they make too much money from from insulin, as well. But they all believe that the future is cell therapy, and they don't want to be like, Polaroid or Kodak, which whichever company was to, you know, be out of the diabetes business because they didn't adjust your business model with the time

Scott Benner 1:21:00
Well, people are still going to be diagnosed, and they're still going to need this treatment. And they'll just find a way to build this treatment to cover the cost they lost on something else. So it's it. I believe that totally. And I think that, like you said that people are smart enough to see that there are other applications and you want to be involved. So what are we looking for here? Do we need, like Beyonce type money to start getting interested in diabetes? Or do we need Elon Musk? Or what level of wealth? Do we need to get interested in type one for this to move forward? You know, I'm saying like, it's not just like, you know, not like a B level actor, we need something else, right? Who do you think Who's your Who's your dream guy who like wakes up one day, it's like, I care about type one diabetes, all of a sudden,

Jeffrey R. Millman, PhD 1:21:45
I, I don't know that I have a good answer to that. I think that'd be a little bit beyond beyond my paygrade. But Elan Musk, you know, going and, you know, sending being the first private company to send astronauts into space. And yesterday, that rocket with his car to Mars, I'm sure that I'm going to guess the amount of money that went into that would be a good amount of money. That's one day that that would definitely help out quite a bit, though, of course, what he's doing with this company is very, very valuable as well. So I don't have a good number for you. But I can tell you that the number number one limiting factor towards progression, for here, it all comes down to money and the limited amount of money that's there. And especially in the world of COVID-19, for which where, you know, there's a lot less money to go around, both because a lot of money thing rejected COVID-19, again, which is a very important thing, but but also, like foundations overall are raising less money in the economy has slowed down a whole lot. There's less money available overall. And a lot of the traditional diabetes foundations that have been very supportive. In the past, I've had to really clamp down in terms of the amount of money they're giving out right now, because their fundraising has been so small this year, versus that years past. And so it's unfortunate that it does seem that COVID-19 is making it so that we were already in a bad situation where there wasn't enough money for diabetes research. And now there is even less money for diabetes research.

Scott Benner 1:23:28
Alright, so I think you know, what we need to do is whatever that powder is, you give the mice that makes their pancreas stop working, we got to slip some of that into like Joe Rogan's coffee or something like that. I think this is the way to get. I'm obviously

Jeffrey R. Millman, PhD 1:23:40
I don't think I would support that.

Scott Benner 1:23:41
No, I don't either. I'm just being Jeff, I genuinely cannot thank you enough for doing this. And I just want to let you go, because I've kept you much longer than I said I was going to, and thank you. And honestly, if there's any thing you ever want to add, and you found this valuable, please come back on. Yeah, this

Jeffrey R. Millman, PhD 1:24:01
is really my pleasure. I really enjoyed our conversation. And I'm hoping that your audience gets, you know, a little more information about what's going on when it comes to diabetes futures, because it really is exciting. And I think there's a lot of reasons for hope. And I hope that message came across in our discussion. So thank you very much for having me on.

Scott Benner 1:24:17
It's my pleasure. Is there any way they can track your progress online?

Jeffrey R. Millman, PhD 1:24:21
Yeah, so I'm very active on Twitter, at Jeffrey r Millman. So that's usually the first place that any announcements about progress come from from from my lab. And we also have a website that is fairly up to date as well. That is kind of a complicated address. But if you just look up milman lab Wash U it should be the very first result in Google.

Scott Benner 1:24:48
Thanks so much to Dexcom and Omni pod for sponsoring this episode of the Juicebox Podcast. Get your free no obligation demo of the Omni pod tubeless insulin pump at my Omni pod COMM forward slash juice box and learn all you need to know about the dexcom g six continuous glucose monitor@dexcom.com forward slash juice box, lend your support to the T one D exchange at T one d exchange.org forward slash juice box, make an addition to that research and help people with type one diabetes to live better. Don't forget to follow Jeff on Twitter, Jeffrey r Millman I don't normally. What I mean to say, I've seen a lot of people cure a lot of mice of Type One Diabetes over the years. This just felt new, a little different to me. And I thought it was well worth understanding the process that got Jeff and his group to where they are right now. I hope you found it interesting as well. I also really thought it was interesting to hear more about, you know, some of the financial support that research needs and, and how difficult it is to get and the you know, considerations behind Do you want to get a regular company involved in this? Or do you want to keep it academic. I like finding out more about you know, the corners of those stories. I really appreciate what Jeff did today, I thought he was a great Shepherd of information did a really good job of explaining it without over promising or you know, hyping it beyond what it was. I hope you enjoyed it as well. Thanks so much for listening to the Juicebox Podcast for sharing the show. There's a couple of great new reviews up on Apple podcasts in the US and Canada and a couple of other places. I appreciate all you guys taking the time. And thanks again, for sharing the show. Just the other day, the show had its most popular downloaded slash stream day in the history of the show. And it was 25% greater than the last most popular day. And as a matter of fact, over the last four months, the show has bested its downloads every month. It's really growing. That is definitely because of you guys. And I really appreciate it. Last thing, if you're interested in a private Facebook group, for the listeners of the show, one of those exists, just head over to Facebook and search for Juicebox Podcast, it'll pop up Juicebox Podcast colon type one diabetes, that's a private Facebook group, you'll have to answer a couple of easy questions to you know, prove your human being. And then once you're in, you're going to see what is now 5500 users 4000 of them are active every day. It's an amazing Facebook group, maybe one of the biggest anomalies in the world might be more of a crazy thing, this Facebook group then telling a cell to make insulin. And by that I mean people are actually nice on Facebook and helpful and thoughtful and not awfully ego and not always trying to prove people wrong. It's a it's an uncommon Facebook group that I think you might like and if you think you can make an addition to it, please jump in. If you're not looking for that much activity, but you want to keep up with the podcast on Facebook. There's also a bold with insulin public group. And if you're more of an Instagram person you're looking for at Juicebox Podcast. Also, if you're looking for the diabetes pro tip episodes to listen to again or share with a friend and you're finding it difficult to dig them out of you know the many many episodes that are there in your podcast app. I've put them all at diabetes pro tip.com. And of course if you have a great diabetes practitioner or you're looking for one, check out juicebox docs.com. Give a penny take a penny kind of an idea you can leave your great endo for someone else or take someone else's and give them a try.