Primodos, a hormone-based pregnancy test, was given to women between 1959 and 1978. Its development occurred before GLP and before standardized testing for teratogenesis (causing birth defects). There are data and suspicions that it caused birth defects, but more questions remain.
This episode of Inside Out Quality explores the story of this in vivo diagnostic with Dr. Neil Vargesson, from the University of Aberdeen, Scotland, UK. Learn another reason for the importance of Good Laboratory Practices and why pre-clinical studies are key to keeping people safe.
To learn more about Dr. Vargesson's research, visit his site here: Link
Dr. Vargesson's research publication discussed on this show: Link
Primodos, a hormone-based pregnancy test, was given to women between 1959 and 1978. Its development occurred before GLP and before standardized testing for teratogenesis (causing birth defects). There are data and suspicions that it caused birth defects, but more questions remain.
This episode of Inside Out Quality explores the story of this in vivo diagnostic with Dr. Neil Vargesson, from the University of Aberdeen, Scotland, UK. Learn another reason for the importance of Good Laboratory Practices and why pre-clinical studies are key to keeping people safe.
To learn more about Dr. Vargesson's research, visit his site here: Link
Dr. Vargesson's research publication discussed on this show: Link
Hi, I'm Aaron Harman and this is inside out quality, a podcast about real life events and experiences shared by our guests of when things have gone wrong, and how we can learn from them to build better products, companies and improve lives through an effective quality system. April 13 1983, a trial began with for scientist, they ran a contract research organization named industrial biotech, Inc, which falsified data and mistreated animals, which is an understatement. Eventually, three from the company got prison time. One of the outcomes from the industrial biotech Fallout was a new set of regulations put in place in 1978, called good laboratory practices. If you remember the season one episode on thalidomide, thalidomide was released into the market for pregnant women without thoroughly testing for safety. Essentially, they hadn't tested adequately, if it would cause birth defects to the developing child. Now we do a battery of tests recommended by the international community and harmonization ich to ensure that the product is as safe as it can be before going into humans. These tests are referred to as non clinical studies, since they don't use humans. How we conduct those tests is a process called good lab practices are GLP. When I talked to Neil Ferguson about thalidomide, we also talked about Primodos, the Primodos story's a little different. The challenge Neil is faced is with data generated now in data generated in the 1950s. I highly recommend you watch the documentary by Jason Farrell, Primodos, the secret drug scandal, I recommend watching it through the lens of a scientist, think not about data, but how the data was generated. I'd also recommend not thinking of scandal, but instead thinking of it from a quality perspective. By the way, quality is very hard to get right. So hard, even the greats in medical sciences have gotten it wrong. Robert Koch once announced that he had a cure for TB, which is another episode maybe about tuberculosis. So even Nobel Prize winners get non clinical studies wrong to do Vargas and studies birth defects and the molecular mechanisms behind them. He is now trying to connect data that he's generated to data for the 1950s. And that's the story of this podcast episode. Welcome back to Inside Out quality. Neil,
Neil Vargesson:thanks very much. It's great to be back. Thanks for the invitation. Definitely.
Aaron Harmon:So first off that you tell us about Primodos? like what was it used for? How did it work?
Neil Vargesson:Okay, so Primodos was a hormone pregnancy test, it was used between 1958 and 1978. And basically, before the hormone pregnancy tests, what you did to work out if a lady was pregnant was the lady would go and see a physician or a doctor, and should either have a physical examination to confirm that he or she would give a urine sample. And the urine sample would then be injected into frogs or toads. And if the front of the toad thing ovulated, the next morning, that a lady was pregnant, and the reason for that is because the same processes that control menstrual cycles, ovulation and pregnancy in humans are similar in frogs and toads. But of course, and so that was successful. But the problem with that was, was that you were going through an awful lot of animals, and society didn't like that. So the idea of a hormone pregnancy test came about, and is where Primodos comes from another form of pregnancy test. And the idea is, is that you take the two main hormones in the lady that are involved in menstrual cycle and pregnancy. So that's progesterone and estrogen, and you make synthetic versions of them if you haven't been reasonably high doses. And the idea is you give this to a lady says she's pregnant. And if you're pregnant, you already have high levels of progesterone in your body. Because progesterone is required to maintain a pregnancy and in a menstrual cycle, as a lady goes through a menstrual cycle, progesterone increases, because she might be getting pregnant. So the idea is, you have this high level just right. Now, if you take this tablet, because you've got high levels of progesterone, the idea was, was that this man made synthetic version would then equilibrate out, and the next day lady wouldn't have a menstrual bleed. But if she wasn't pregnant, because progesterone increases in pregnancy, and because progesterone is required to maintain a menstrual cycle, when the menstrual cycle comes to an end, progesterone goes down. And that's what causes to menstrual bleed. Well, if you're not pregnant, you're being given a high dose of a synthetic manmade progesterone. This gives a peak of progesterone, which then quickly is lost. And that induces a menstrual bleed. So if you weren't pregnant, you'd have a menstrual bleed the next day. And if you were pregnant, you would not have a menstrual blood, it was believed that you were then pregnant. So they would give the lady a second dose, just to make sure. And if she still didn't have a menstrual bleed, then she was deemed pregnant. So this is how it worked. It was on the market till 1978 When it was withdrawn. And that was because of the what we use today is antibody urine stick based tests where you put urine onto a stick and an antibody tells you whether you're pregnant. So there will be being used in Europe, particularly for about 20 years. And some people had false positives. They were told they would they were pregnant, but they weren't. Some were told they were not pregnant when they were and so it was not the most accurate test to have been done. But it did move away from the use of animals. And of course, where we're at now, is that There are a large number of people in Britain in Germany, particularly, that claim that the use of this hormone pregnancy test in their early pregnancy led to birth defects. And I guess, if you think about it, logically, if you're a woman and you're expected to get pregnant, you might take this, you might go to your doctor for weeks, as soon as you've missed your last menstrual period, then you're taking this medicine. But if you weren't expecting to get pregnant, you might not take it for six, eight, even 10 weeks. So you can see that there was a large window of time, and depending on whether the woman was expected to get pregnant or whether she had no idea, and then taking this medicine. And so you can see, as we discussed in the previous podcast I did with you for thalidomide, that that time window between four and 10 weeks is when an awful lot of development is going on in the embryo. So that that's that's the background of Promodos is no longer used tool, but the components of it are. And one of the components, which is norethisterone acetate, which is a synthetic progesterone, manmade, and is now used in things like contraception tablets. So it's actually it's also the the major component of one of the morning after pills. And so the irony here for me, is that you've got a medicine for a component that was used in Primodos are very high doses to confirm a pregnancy. But today at much lower doses, it's used to prevent a pregnancy. So there's some irony here. And we got involved because I saw newspaper reports talking about the forgotten, solidified. And if you remember, I'm a bit obsessed with the Linamar and how they might work. So I got involved, because I wanted to see if we could find out from Primodos, how it worked. But then would that shed light on third of mine? And it turns out, it's become a whole new project of its own. And we're now trying to understand how this drug works. And did it cause birth defects? How does it cause birth defects? And looking at the molecular mechanisms? So that's in a nutshell, what the what Premadasa is, what is alleged to have done and what we're doing in a nutshell,
Aaron Harmon:when was their clue that there might be something wrong with Primodos?
Neil Vargesson:So this was back in 1967, a pediatrician in London, the UK is about gal, she published a paper in Nature, which is a very prestigious journal. And she said, present some data that's that linked provement, or prevalence in hormone pregnancy tests with causing an increase in Spina Bifida in babies that were born to mums that took home pregnancy tests. And that was really the first the first alarm bell. And then there were some other papers that came out soon after that sort of exacerbated and suggested there's some other problems. But this is where the problem started to come in. Because other groups said that there were there were no problems. And there were animal experiments done in the 50s 60s and 70s. And there were some experiments and said, Yes, Premadasa hormone Princey. Tests can cause problems. And there were some that said, No, it didn't. And it turns out that it's due to methodology changes, right, and differences. So in those days, people just did their testing in very different ways than we do them today. We don't have the imaging that we have today, we don't didn't have the molecular analysis that we have. In some studies, they gave the the drug in the animals food, well, how do you know that the animal ate all that food and all of it got in the bloodstream, you don't, it may or may not have even touched it. So if the embryos come out normal, you think that the drug isn't doing anything, but you've got no idea where it got into the animal anyway, in other studies they did coverage in which is where you, you put the tube into the animal's stomach, and you put the drug in. And again, you that that's, that's the best way to do it. But you don't know if all of that drug was got inside into the embryos or parts of it, because you just can't tell. And so there were lots of different differences in methodology differences in the way they were analyzed, and different interpretations. And if you want to find a paper that says hormone pregnancy tests cause birth defects, you'll find them and if you want to find one that says it doesn't, you'll find that too. And that's the problem with the field. It's, it's, it's that sort of, you know, 1950s 60s 70s science that we were looking at, nothing's been done since. And you're looking at papers that use very, very different methods and ways of doing things. So it came about with the 1967. And then since then, we've had epidemiology studies linking it, and some studies saying no, it didn't. We've had scientific papers say that there's something something No, it didn't. And that that's that's where we're at.
Aaron Harmon:If I was developing a drug today, that was going to be used and could have potential impact on field development. What kind of studies would I do to determine if it does or doesn't cause issues?
Neil Vargesson:Yeah, that's a little my disaster change the way we test our drugs right? And we we now have to do multiple clinical trials, you have to test your well first of all, you have to test for drugs in multiple species to check that the drug is doing the same thing in different species or to also to check the there's no species specific differences, like we found with the minimize vision then you go into clinical trials where you have four or five phases. And the the idea of that is that you would test your drug in a different range of conditions. So that would be adults, young adults, maybe wouldn't be in pregnant people, cuz we're not allowed to test in pregnant people. But you would still test that in pregnant animals in different species. And the whole, all of that together would then tell you whether the drug was a risk. And if it was deemed to be a risk, but the benefits within to outweigh the risk, as long as precautions were in place, such as you would be if you had a scheme, for example, that made sure that people were on contraceptives, taking regular pregnancy tests, so that you reduce the chance of a pregnancy, that's fine. But if the if it turns out that the drug the risk outweighs the benefit, then you wouldn't, you wouldn't release it, right. So there are due to the thalidomide disaster, we now have an awful lot of measures in place to check drug safety, that includes additional animal testing, as well as clinical trials. And we haven't had a disaster like that, that solidify disaster since we've had a few caveats to that, but the majority of testing is much better than it was. So that's what you would do you have a multiple animal tests, and then you have clinical trials. And then if there are problems, you have to decide whether there's a is more benefit to have the medicine or not. And if that's the case, then you would put in safety protocols and safety precautions. So for example, if you know a drug could cause a birth defect, you have these protocols where you advise people that are taking that medicine that they are to get pregnant, that they take a lower dose, and they take it less frequently. And the idea is that you reduce the rate. So there are there are things in place, and they're very effective. And we just have to keep reminding the public and the government that we need to make the drugs as safe as possible.
Aaron Harmon:Yes, definitely. And so you've done studies now with Primodos in your lab out kind of data. Were you finding what kind of models were using? How that story unravel?
Neil Vargesson:Yeah, so we, as I mentioned, I heard about the Forgotten flutamide. And it's instantly pricked my ears up so I have to have to find out about it, because got the word thalidomide in it. And when I did the literature search to find out what what was known about Premadasa in embryos, you realized that the last real experimental work was done in the 1970s. You know, you could either find a study that said it did cause problems, or what didn't. And all of these studies were done in rats or mice. So when rabbits, and as I say some of them said they were problem causing problems and subsequent did in my lab, we work with the Linamar. And we do drug screening to test safety of drugs. So I just put them in the assays that we use. So we use primarily profesh. For this, because zebrafish embryos develop so rapidly, they share 70%, of the human genome. And of that 87.5% of that genome is is commonly is common genes that you see in human birth defects. So we put them on two separate fish. And we found that with high doses, this drug, when you apply it directly to zebrafish embryos, you get problems, you get problems to the head, to the brain, to the nervous system, the blood vessels, the ears, the eyes, and the spine. And we also didn't take it and put it into culture, where you put it onto endothelial cells as blood vessels that are derived from humans, it causes problems with those. And also, if you put it into culture, with nerves derived from mice, those nerves are damaged as well. So it was causing a range of issues. And we published that in 2018. And it caused a view got a lot of media interest. And we featured in a couple of documentaries on Sky, Sky News in the UK, looking at Primodos and its history. And it led to some government reviews. And it's led to an independent medicines and medical devices safety review. So it's quite significant. However, the doses we were using, were quite high. And the reason for that was because when you're testing a drug, you want to you want to see what it's doing. So you sort of kind of put a dose in that you think is going to cause of having an effect where you think might cause an effect, you see. And when so we used to read the high dose, we found these problems. So what we've now done is we've now use much lower doses. And these cause much more subtle damage. And what I mean subtle damage, I mean, like, instead of seeing a gross malformation, like you know, a brain defect or missing limb or missing thin or missing ear, you get smaller ones instead, then you have to measure them to show that the eyes are smaller, the hearts got still got a problem. And these are subtle that if you if you weren't looking for it, if you didn't know it causes problems, you might have missed that. So that's the beauty there's a proficient because these are proficient develops outside mums body you can follow these things live. So we've now found that and we've also done some molecular screening looking for molecular targets of Primodos in zebrafish embryos, and we found a couple that are very interesting. And what we're now doing is we're now trying to validate those targets. And we're trying to validate those in other embryo species but also in human cell lines. And if we can validate them, and we show that they are important developmentally, then this this gives us a bit more A bit more weighted, you'd like to suggest that should that drug I've got to got to a human embryo, then there's a chance it could have caused the birth. But we're still a bit far away from that particular point at the moment cuz we still need to validate it. But it's very exciting because we've got these targets, and we're trying to validate them. And I think this is the first time this has ever happened. So that's great. Because the question we get asked a lot, which is quite right, is that as every fish embryo is not a human embryo, and it isn't, they develop very similarly, on my ad, they go through the same processes that we go through, they go through cell proliferation they go through elongation of the embryo they produce eyes is thins in turn internal organs the same way that I was formed. So they are very similar. But the big difference, of course, is that as human develops inside mum with a placenta, whereas a fish does not, and we're applying the drug directly to the zebrafish embryo. Now, the quick, the big question is, did Primodos cross the placenta and get into the embryo? And that's what we have to find out. So we're hoping that these molecular targets will shed some light on that as well, because we're hoping that some of the targets we've identified may be involved in placental transport. So we're hoping that this molecular screen will answer many, many questions. And it may or may have not answered the question that it didn't do that. And if that's the case, that's the case. That's what the data tells us. And we'll see what happens in the next year or so.
Aaron Harmon:Now, we'll take a quick break to hear from one of our sponsors.
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Aaron Harmon:It sounds like what you're doing is exactly what you would do is if you're starting a new drug development program, where you would want to do these screens and using zebrafish looking at cell culture, seeing and putting high doses into CVC signal. And then if you do you begin asking the questions, what's the what dose can you get into without causing those problems? Or is there a mechanism behind it you can identify?
Neil Vargesson:Absolutely, this is we did the same with minimize, I do it with other drugs as well that are alleged to be to antigens, you take the drug, you put it on at high doses, you work out a dose response, where you work out what doses kill, and what doses cause a bursty fatal damage, and what doses do nothing. And in our experience, there isn't a dose of causes that is safe with this truck, when you put it directly on two separate fish embryos, he really low doses cause problems, but really subtle, you really have to look for them. And molecularly with identifying targets, we within really quite quickly after putting the drug on so then you're absolutely right. That's exactly what you do your dose response, you don't do a time response when you put the drug on at different time points of development to see if there's a time sensitive window that the drug acts over. And then you would from that you can work out what's going on. And then you need to validate it, you need to do that in other species, and you need to then start looking for molecular targets. So yes, we're doing everything that you would you would do if you were looking for safety. And that's what we do. The big
Aaron Harmon:difference between now and 4050 years ago, is they weren't requirements back then like they are today. Like if I was going to submit a new drug application to the FDA, they would go through and ensure that I've done this testing if my indications would involve pregnant women, but there was a time where that was not the requirement.
Neil Vargesson:The I agree the we do things very differently today. It's much more stringent these days. And the what was done in the past. I honestly, I'm not that old. So I don't know what the rules were exactly in that in that era. But I think you're right that it wasn't a requirement to test on pregnant animals in those days. But it is now and so that might explain why, you know, so many drugs in the era, the 50s 60s 70s causes problems. But we are not in that position anymore. We do have much more robust and stringent testing. And I'm testing these things now. Premadasa solidified. Remember, I remember Primodos is no longer used hasn't been used since 1978. And part of the problem of understanding the mechanism of action of Primodos is purely because it's no longer yours. So you can't get funding to investigate do research because the funders are like saying, well, what's the point because the drug is no longer in use, but the components are. And so you're going it's like the lid of minds. Well, you're going backwards to try to find the answer, which today with no right if I'd like to think that most drugs that come on the market have been tested correctly, we know that they're safe. We may even have a molecular mechanism We have a much better understanding of what it's going to do. And if you if you go to a chemist, or pharmacist and you ask for a packet of tablets that get rid of headaches by Advil in the US or paracetamol in the UK, you come up with four or five pages of contraindications and things that could go wrong. Because we know a lot more about drugs today. We know when you shouldn't take that with something else. And you know what you should take it with, and don't take it if you've got this condition or that condition. But we didn't know that in those days. And that's, that's part of the problem.
Aaron Harmon:top part of this potential problem curious about is we follow good laboratory practices when we do these types of studies now, and the good lab practices really entails looking from the facility you use, the animal models you're using, how they get fed, what material they're getting fed, all of those practices, or all those things involved with the study down to is the equipment you're using calibrated, and then it's captured into a protocol. And that gets completed, all the things are documented, that's done. And then all of its in report. So it's easy to really connect all the dots and understand the experiments that were done. So we do that now. But that wasn't in place prior to 1976 in the United States. And so if you're trying to like piece together, and you're describing finding studies that say, yes, it causes birth defects, no, it doesn't. Are you able to find all the information to really see how those experiments were done?
Neil Vargesson:That's the That's the crux, right? Because the papers, scientific papers were also written and published in a different way in those areas as well. So you didn't have to give the, you know, the detail that we give today is much more detailed in papers as well. So you can get some information from the papers, but not as much as you would like. And certainly not as much as we would be required to write out to that. So again, it's it's it's a different era and a different way of doing things. And I think, a different understanding. And I think there was a belief in the in the 50s 60s and 70s, that the placenta would protect the developing embryo from lots of different things, which we know is not true. And the placenta basically will filter most things through a lot of things, in fact, so no, getting getting the information that you want is difficult, because the questions I have and the things the protocols are we now use today, if you go back to those papers, you're trying to see that in those papers. But that's not how they were written. And the authors of those papers are no longer with us, or they've retired or they're difficult to get hold on to. And even if you do, the work was done so long ago, they can't remember the the actual methodology that they use, perhaps. So this is the problem when you're going backwards to try to go forwards. If you like when you're trying to find these things out. Retrospectively, it is hard. And I completely agree that things were done differently in those days. And things are much more stringent now. And you have to keep a record of everything these days, which is good. And I'm not so sure that that was the case in the 50s 60s and 70s. So, but we certainly have got advances in imaging as well. So when I work on zebrafish embryos, primarily because I think they're great, they develop outside the body, so you can watch them. But if you're working with mice embryos, you can't see them develop because they're inside the month. But today, we now have ultrasound scanners, right, and you have imaging techniques, you can follow development in the mouse, you can check they are pregnant, and you can check how many embryos they've gotten over a period of time, you can see if any have been resolved, that sort of thing. We just didn't have that in those days. So if if you did give a drug to a pregnant animal in those days, and it ended up not being given any embryos, you've got no idea that was because those embryos were resolved because they were malformed. Or the mom was never pregnant in the first place. And so that's that's how some of the data that comes across is that you just don't know, what are the animals pregnant in the first place? Or what are they never pregnant, but you're assuming that they work, because you've got no way of knowing. So it's lots of different things like that. That is why we are still where we are today, which is we still don't know how Primodos works. And we still don't know, for 100% certain if it did or did not cause birth defects. And that's because we just, there's only me, I think I'm only aware of my group at this moment in time. It's published recently on experimental studies on Primodos. And that's probably because the drug is no longer used. So that's the crux of the problem that we're facing at the moment.
Aaron Harmon:And people get it, you described the argument that it shouldn't be funded, because it's not a product to the market anymore. But it really is also in just different forms. You know, is there a further argument to be made that understanding the mechanisms of some of these other drugs could lead to new drug development out of it as well?
Neil Vargesson:That's the argument we're using. Yeah, absolutely. Especially with the linear mind because you've got all these new analogues of thalidomide or variants of them that have different actions. And they could be used for other treatments. Yeah. So we, that's the argument I use when I write grants, which is you know, yes, these components, this particular drug itself is no longer used for Primodos, but the components norethisterone acetate and Ismar least redial are as I say, norethisterone And acetate is used in the morning after pill, contraceptives. But it's also used to treat gynecological conditions such as endometriosis, as well as breast cancer. And it's in much lower doses than what was used in Primodos. But we don't know what the side effects of that are. And it's thought to be safe. And I know that the authorities in the UK and in Europe, as far as they're concerned, they've seen no new data that says that those components have side effects. But personally, given the evidence that we were seeing, and some other epidemiological studies, I, I think more work is needed to be 100%. Certain, this must be the same for many drugs.
Aaron Harmon:Exactly. And that's, that's kind of thinking as well, because there's, there's other products out there where I know, there's been hesitancy to to reevaluate them with new instrumentation, new technology, new experimental methods that we have, for fear that they might find something negative. But I think at the end of the day, the data you generate will trump any of the negatives because it could lead to other uses a better understanding of the safety profile? And in the long run, you're going to win by generate that data?
Neil Vargesson:Yes, we'd like to think so. And as I say, I mean, I'm going to be brutally honest. I mean, I'm a scientist, and I go, I let I let the data lead us. Now, I haven't spoken to survivors, alleged survivors, sorry, of Primodos in the UK, and some in Germany. I've told them that it might well be that our data actually comes down the other way that it actually says this drug did not cause problems. And then all of their responses was, well, that's fine. As long as we can see the data, and we can see that it's, it's, that's what it says, and it's transparent and clear, then we'll be happy. But equally, they don't believe that's going to be the case, they feel that we're going to find out that it is causing response. But I'm we're not at that point, yet. We still have work to do. And so, you know, we'll see in a couple of years time, but it is a problem when the field is the way that it is is that no one's specifically working on Primodos anymore. Yes, the components are out there. But no one's really looking at those because they're deemed to be safe. And you're on your own really. And you just have to do what you're doing your hope that your work can least bring some closure in some way, whether that's in a way that says No need if this didn't happen to you, it's something else that caused your birth defect or as there is a chance it did. And when you're working on in a group like mine, we run around with there's no it's not like it's about 15 people working on this truck. It's me I think it there might be some others I'm not aware of. But there's very it's a handful of people at most, right? So it's going to take time. Did that answer your question?
Aaron Harmon:It did. And I'm also wondering, too, there's tons of basic science research that happens to just explore how things work in biology or in the world. Are there other discoveries that may lead from this kind of work as well, that maybe isn't related to, you know, something about impact of the drug, but maybe underlying mechanisms in fetal development as an example? Yeah,
Neil Vargesson:this is why I do what I do. Because ultimately, we want to know how you go from a single cell to a fully formed human being right, or a fully formed organism with one head, two arms, two legs, five toes, five fingers on each hand. And so if you understand how drugs work in a bad way, how they cause a birth defect or, or what influence they have on an embryo, whether that's they cause an increase in cell proliferation, so cell division, or whether they enhanced the number of blood vessels in the tissues. If you if you know how a drug does that this will help you understand development, it will help you understand how embryos formed. Because right now, we still don't know that there's some basic questions we still don't understand. So in my mind, understanding how drugs, like thalidomide cause birth defects, or like Primodos, and they may or they may not cause birth defects, ultimately, what's going to come from that is a better understanding of the molecules that those drugs target in the embryo, and a better understanding of what those molecules would normally do. So not only do you have our work, I hope, helping to bring closure to people when ultimately, when we put the end to the story, but hopefully, we'll identify molecular targets, which will shed light on how the drug acts, making safer forms those drugs if need be, but also shedding light on normal developmental processes. And that may, that may lead to other therapists, it might lead to a brand new gene target that we hadn't thought of before. And all of a sudden, that becomes, you know, a gene of interest for other conditions, where it might just allow us to understand a bit more about why development is the way that it is. So to me, it's what drives me all these different things. It's, you know, how does an embryo form normally? Why does it go wrong? How did drugs cause these problems? Can we understand the molecular basis of these drugs, action? Can you make safer forms of drugs? Can you eradicate birth defects from drugs, and then ultimately, will shed light on normal processes?
Aaron Harmon:That's great. It's like reading the story of biology. I went to get the more you learn?
Neil Vargesson:Well, this is a nice thing. But I'll tell you now, I got involved in development of biology a long, long, long time ago, I got into evolve into littermate, what, 2020 years ago. And I have more questions today, on embryology and how drugs work than I did when I started, which is a good thing, because it shows we know an awful lot more. And that's opened up more questions. But it's, you know, the my idea of, I would solve some of these problems before I retire, I'm not so sure it's going to be the case.
Aaron Harmon:I was describing this to someone yesterday, as if you had taken the Model T car when it was first produced, it could have met all of your quality requirements at that time. But with feedback with technology, with customer needs and desires, that product continue to develop, develop, develop, develop until the cars we have today on the road, I think it would be crazy to think that in 100 years from now, cars that are being produced will look exactly like what we have now. And I feel like that same process applies to drug development, where we start somewhere. And as we get more data, and we learn more, we continue to develop and modify and get better and better and better. And, and who knows where the future is going to go with this?
Neil Vargesson:Oh, absolutely. I mean, that's, you're absolutely right. Are the drugs that we use today to treat headaches? For example? Are they still going to be used in 20 3040 years time? Or are we going to find something that's much more effective with less side effect? I mean, as we discussed, I mean, if you go to a pharmacist and you ask for some Advil, you're given Advil when you've got pages and pages of Contra indications, right? Well, that's, that's great to know. But it are we going to get to a point, you know, I think we could we get to a point where you can take something specific for you. And specific for a headache, or specific for foot ache, or whatever it might be, that doesn't have any, any problems. And that's what that's what I think we can do is solidify, particularly, because you can now make versions of thalidomide that don't cause birth defects, right? They don't, they don't damage embryos, they have other actions, that the drug is very useful. Well, hopefully, there'll be on the market at some point. So I completely agree, that's how you should be looking at drugs, you have to bring in new drugs, to replace the existing ones that make them safer. And ultimately, in 10, or 15 or 20 years time, I'd like to think that a lot of the drugs that we're using today won't be on the market, but we have much more enhanced ones. And they call it personalized medicine, right, where you get drugs, for very, very specific conditions, and almost on an individual basis, and with genome analyses going the way that they are, who knows when we maybe maybe even be able to design drugs for an individual person for a specific condition. I think that's very realistic. It's a long way off, but I think that's possible. But to get to that point, you need to understand the basics, you need to understand how do the drugs we currently use work? What are the side effects? How did the side effects come about? Can we stop them but keep the benefit of the drug in the first place? And if not, can we can we make a new drug that has the benefit without side effects? So there's a long way to go. But I think you're absolutely right. And I think the analogy with the cars is a nice one, that we've always had cars, but they've completely changed from when they first came on the road. And their safety is is amazing now, right? I mean, all these different safety mechanisms, airbags and things like this. Same thing with drugs, I think we do need that we do need to keep moving forward, making them as safe as
Aaron Harmon:possible. And we're going to get there with the help of zebrafish.
Neil Vargesson:So zebrafish, zebrafish, they're great. They develop externally, they go from a single cell to a fully formed fish embryo in 24 hours. So you know, very quickly, if your drug or your compound is causing a problem, they share 70% of their genome with us of which 87.5% are disease to genes that you see in humans. And yes, they're tiny compared to us. And they develop far more rapidly than us and they develop outside the body. So there are differences. But they are a great tool to to understand if there's a potential for a drug to have a harmful effect
Aaron Harmon:on a human. That's why we use Well, thanks for joining us, Neil.
Neil Vargesson:It's a pleasure. Always, always good to talk to you and, you know, anytime,
Aaron Harmon:and thanks for tuning in. We hope you enjoyed this episode. This is brought to you thanks to South Dakota biotech Association. If you have a story you'd like us to explore and share, let us know by visiting www. SD bio.org. Also, if you live in the Sioux Falls area, check out quinnbet A local Quality Assurance Professionals Network. You can find out more about COVID by clicking on the link on our website too. Thanks for listening