Chirality matters in medicine because the two mirror-image forms of a molecule can have completely different effects in the body, making pure enantiomer production a key goal of pharmaceutical manufacturing. The hosts use the thalidomide scandal of the 1960s as the central example: thalidomide was given to pregnant women for morning sickness, and while one mirror-image form acted as a sedative, the other caused severe birth defects in tens of thousands of children worldwide. They credit FDA pharmacologist Frances Oldham Kelsey with blocking the drug's approval in the United States despite pressure from manufacturer Grunenthal, sparing the US from the crisis that hit Japan, Australia, and much of Europe. The discussion frames understanding nonlinear effects in asymmetric synthesis as directly useful for identifying active drug forms and improving selectivity in drug design.
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Kennedy awarded Kelsey the President's Award for Distinguished Federal Civilian Service for her role in blocking the drug.
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The hosts note that Grunenthal only issued an apology roughly fifty years later, after many of the original executives and scientists had died.
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One host connects the topic to his father's work in stage-one drug discovery as a personal link to the science.
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51:29that connect to the impacts now that we have this understanding? Yeah, and this leads to like, you know, some of why chemists are so motivated by this. The aim is to produce enantiomers that are as pure as possible. For example, in pharmaceutical manufacturing, you want a particular type of handedness for the drug that you're making. You don't wanna do Louis Pasteur where you've got both sides. The importance of achieving this has been shown by the thalidomide, the thalidomide scandal of the 1960s. I don't know if you're aware of this. No. I was not. But this is an incredibly dark time in chemistry, in pharmaceuticals, and in the world at large.
52:11Like, aside from war, this is one of the worst disasters in history that I hadn't really heard about, which I was really surprised by. So this is the thalidomide scandal of the 1960s when thousands of children were affected by birth defects caused by a sedative, thalidomide. It was widely given to pregnant women to treat morning sickness. It's actually incredible that like, there's so little testing on pregnant women to create such a tragedy. Tens of thousands of people were affected. And when researchers analyzed what had happened, they'd realized that it was an active substance. The mirror image was causing the harm, right?
52:53Both mirror images were in the drug. And while one of the mirror images was actually creating the sedative version, the other mirror image was causing these defects. And I wanna take a brief note here and talk about why the world at large was very much affected by the thalidomide scandal. Tens of thousands, I'm talking literally tens of thousands of birth defects. The US was spared because of Frances Oldham Kelsey. And if you go back to that photo that we had, Frances Oldham Kelsey is the hero in our story for America because she was a pharmacologist
53:34working for the US Food and Drug Administration. She blocked the drugs approval in the United States despite heavy pressure from the manufacturer Grünenthal, which was a German pharmaceutical company. They were trying to pressure the FDA to approve this thing. She saw the writing on the wall in early clinical studies that others had kind of just hand waved as like, oh, that's just a hand of God, like chance stuff. She was looking at the data going, no, no, there's clearly an effect here. I don't know what you guys are talking about. She received a lot of pressure from lobbyists, from like, I can imagine like as a woman at the time in the 1960s in the Food and Drug Administration as a scientist trying to
54:19block approval, but it took her and it largely spared the US from this crisis. There are several other countries that are still dealing with this, Japan, Australia, a lot of Europe. These are developed nations that have their own versions of the Food and Drug Administration, but somehow the pressure from Grünenthal, like actually, they succumbed to that pressure. We did not because of her. And there's a photo of President John F. Kennedy giving her the President's Award for Distinguished Federal Civilian Service. It highlights why the FDA is important. I wanna bring this up in today's climate where apparently we're just making decisions
55:05with the FDA that don't make sense to me, don't make sense to a lot of trained scientists. I just wanted to show that this is one of those situations where you really need independent thinkers in our government to make informed decisions. America was spared from that crisis. When the next crisis comes, we need someone like Francis Oldham Kelsey to do that again. And just to piggyback on that, I think this also highlights the importance of not allowing commercial influence in sort of public health decisions. 100%. As well as
55:45research and R&D decisions. There needs to be a healthy tension there. And this is a perfect example of, you don't want it to become too late because you've allowed sort of this runaway corporatism to infect civic institutions to their own benefit for the sake of shareholder value at the expense of a potential catastrophe that can last generations. And these decisions can last generations. And these countries are still dealing with it to this day. I think it was only the last decade when that-- The German company. Yeah, very good.
56:27Yeah, but only in the last decade was that company actually apologizing for what they did, which is like 50 years later. Really? And a lot of, I mean, I went in a deep dive on this. A lot of like the original scientists and shareholders and the CEO of that company in the 1960s that was peddling this thing, they were just trying to avoid any sort of responsibility. They avoided responsibility for most of their life until most of them had passed away and then they had the repercussions. If you guys wanna like go into a deep dive about how badly things can go wrong, you should look up the thalidomide scandal of the early 1960s.
57:08But I think this highlights something about drug development, which is chirality is a practical design and quality control issue, right? If two mirror images interact differently with the body, then the manufacturer needs to understand which form is being made, how much of it is being made, and how we can actually create asymmetric synthesis where we can build a preference of one over another, right? Understanding these nonlinear effects helps researchers interpret experiments, identify active species, and decide how to actually improve selectivity. So this year's Nobel Prizes, the work that they've done is very much important for drug development at large.
57:48This is, it's so interesting. I think, you know, I've talked about this previously. You know, my dad has worked in stage one drug discovery for quite some time. And this is one of those things where, you know, even in the course of his career, the change of understanding has impacted what he's been able to do and work on. And it's always touching on stories that have a tangential connection to allow me to understand his work a little bit better. I always find gratifying. Yeah. And I know you feel the same when we talk about stuff in the other category for you as well.
Nobel PrizeChemistryBiochemistryChemical origin of lifeSynthetic Biology