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🎙Two Docs Talk: Developing Natural Products: Part 1 - Unraveling the Intriguing History of Nature-Inspired Medicine Ep 136

• Dr. Michael Koren, Lisa Kirvin Dawes • Episode 136

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Get ready to embark on an intriguing journey through the history of medical advances rooted in natural substances. I, your host Dr. Michael Koren, had the pleasure of inviting an old friend, fellow Harvard Medical classmate, and a champion of Jamaican medicine, Dr. Lisa Kirvin Dawes, for a deep dive into this captivating subject of developing natural products in a 4 part series. From the story of ether anesthesia's origin at college parties in the 1700s and its transformation into a medical revolution to the significant impact of everyday substances like opium, morphine, and taxol on modern medicine, this episode is packed with fascinating tales that showcase the deep connection between nature and medical innovation.

Discover how experimentation, controversy, and the power of publication paved the way for some of the greatest medical innovations of all time. As we venture into the details of the opioid epidemic and groundbreaking cancer treatments, you'll get a glimpse of how these naturally derived substances have evolved into indispensable medical tools. This exploration isn't just about scientific breakthroughs; it's also a testament to the importance of documenting and sharing knowledge, as exemplified by the story of ether anesthesia. So, join Dr. Kirvin Dawes and me as we unravel the inspiring saga of nature-inspired medical breakthroughs.

Full Series:
🌿Two Docs Talk: Developing Natural Products Pt 1 - Unraveling the History of Nature-Inspired Medicine
🌿Two Docs Talk Developing Natural Products: Part 2 -From Ether to Red Yeast Rice
🌿Two Docs Talk Natural Products Part 3 The World of Psilocybin Therapy & Marijuana Regulation

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Music: Storyblocks - Corporate Inspired

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Speaker 1:

Welcome to MedEvidence, where we help you navigate the truth behind medical research with unbiased evidence, proven facts powered by Encore Research Group and hosted by cardiologist and top medical researcher, Dr Michael Coran.

Speaker 2:

Hello again. My name is Dr Michael Coran and I'm your host today for this episode of MedEvidence in our two docs talk series. I have an incredibly special guest today, and not only is she incredible just as a person, but she's also incredible in my life, because this is Dr Lisa Curvindaz, who is actually my medical school partner at Beth Israel for third year clerkship in Neutral Medicine. Do you remember those glorious days.

Speaker 3:

Lisa, yes, I do, the night calls yes.

Speaker 2:

Yeah, so we were both Harvard medical students together back in the day and Lisa and I became lifelong friends and also resources for each other, because Lisa is a world of knowledge. She trained in internal medicine, then she trained in public health. She worked in New York for a while while I was there, moved to Maryland to do some work and then moved down to Jamaica, which is part of her roots, and has been practicing medicine in Jamaica and is a leader in medicine in Jamaica as we speak.

Speaker 3:

Thank you very much for having me, yeah thanks for joining us today.

Speaker 2:

So we thought a neat thing to do would be to talk about how medicines develop from interesting natural means. So we have a pharmaceutical industry right now and the pharmaceutical industry has its ways of discovering new compounds and new ideas for therapies, and nowadays there's more and more biological therapies that are based on genetics, but a lot of really cool stuff developed just by observing nature and observing natural things and then coming up with therapies based on those observations. So we're going to talk about that today. Because of the fact that we met at Harvard and Harvard has one of the interesting traditions, which is the place where ether anesthesia was developed. I thought maybe we'll start with that. Lisa and I obviously are friends and we've been to parties together and they serve alcoholic parties and that's part of our culture and ether actually came from that idea, that cultural idea of having a party together and getting a little intoxicated.

Speaker 3:

Getting a little high.

Speaker 2:

There you go. And so back in the late 1700s and the early 1800s, particularly in the UK, the chemist that were working there was this guy named I think his name was Humphrey Davy who discovered a lot of the elements of the periodic table, including sodium, and him and his buddies would figure out how to mix things together and create all different substances. So they figured out pretty early on that if you combine alcohol with sulfuric acid it gives off a gas and this gas turns out to be ether. And then if you sniff this gas you get a little buzz and they would have ether parties. That were the rage amongst college students back then, starting in the UK, but they started doing this in the US as well. And then obviously physicians who are often college educated not all, by the way, back then a lot of them were they kind of took this college tradition and they started thinking, well, how can we use this?

Speaker 2:

And back in 1842, crawford along was a surgeon practicing in the South in Georgia, and probably based on his college experience of sniffing ether at parties, he kind of figured out that you can use it to give people pain relief during surgeries. So he started doing surgeries where we got his patients to sniff the ether and they fall asleep or get intoxicated and know what's going on and cut off their toes or whatever he had to do for surgery. So this was going on for a little while. In simultaneous with that, there was a guy named Thomas Morton. Actually it was William Thomas Morton.

Speaker 3:

The dentist.

Speaker 2:

Yeah, he was a dentist, Very good, and he married somebody who was a very, very fancy family in Boston Boston was very snobby back then and he married the daughter of a congressman, if I remember correctly, and they said well, you can get married, we're not crazy about our daughter marrying a dentist, but if you take courses at Harvard Medical School then we'll let that happen so you can bring yourself up to a higher station. And so Dr Morton did that and back in those days you didn't. You basically paid for lectures at Harvard and every other medical school, so it wasn't such a formal program, but you would go there, you would have the famous professors of the time or the prominent people of the time giving lectures and the students would pay a fee for the lecture and then you took enough for those lectures and you could say well, I was educated at Harvard. So that was kind of the way things work.

Speaker 2:

So he started taking lectures at Harvard and got to know some of the people there, and he was also a little bit of a entrepreneur. He was trying to figure out how to make money doing things and he eventually showed that in his dental practice he was able to put people to sleep and extract teeth and do things of that nature. And then he approached Dr Warren, who was a very prominent surgeon at Mass Journal Hospital, and said I'd like to show that you can actually do a surgery while somebody's asleep from ether anesthesia. And they set up this big event back in I think it was October of 1848 in a place called the ether dome. Then you've had some experience there. It's this amphitheater that has these very tall, narrow chairs that are incredibly uncomfortable and that's, they still have those yeah.

Speaker 2:

Well, when I was there, they did.

Speaker 3:

We graduated at the same time, so that was I was hoping no, but I was hoping they would have changed that, Because I don't think they would change about that because it's a national monument, I think, to preserve it the way it used to be.

Speaker 2:

But they were incredibly uncomfortable, hard wooden seats that we took lectures in their medical school and you can never get comfortable in them. But it was an operating theater and they actually started showing operations back way before ether anesthesia. If I remember correctly, it was like in the 1820s where they were doing that and then in 1848, there was the first public demonstration of using ether as an anesthetic for surgery and John Warren was a very prominent surgeon. He agreed to work with Morton, who was the anesthesiologist, and they did a painless surgery. But the interesting part of the controversy is that this was being done by other physicians, most prominently Crawford Long and the Mass Journal. People got all the credit because they published it.

Speaker 3:

So that that means that if you don't publish, you don't get any credit.

Speaker 2:

Exactly right. It's a really important part of the story is it doesn't matter who comes up with the idea. It matters who publishes the idea, but by publishing it, they also were much more structured than what Crawford Long did, which is a theme that we talk a lot about here at MedEvidence, and that is that you can have a great idea, the great idea may even work beautifully, but unless it's part of some sort of structured experiment, you're not going to get full credit for it, nor do you know how good it is. So back then this was set up with the New England Journal of Medicine or whatever the precursor was, and they had the press there and they had a protocol that they followed in terms of using anesthesia and then, ultimately, during the surgery, they picked a patient ahead of time. They got the patient's agreement to be part of it and, lo and behold, they show this publicly and it was published by the New England Journal.

Speaker 2:

It got picked up all around the world and it was actually the first time that the Europeans who are very snobby about their advances in medicine at that time they were first is the first time the Europeans actually gave the Americans a little bit of respect for coming up with an innovation and it kind of launched certainly the preeminence of American medicine in surgery and ultimately it was the first major breakthrough where American medicine introduced an idea to the rest of the world.

Speaker 2:

So that's an example of going from a party drug to something that really revolutionized how we do things in medicine and based largely on having a simple structured experiment and publishing it. So there's been a debate about I know this still goes back and forth about should Crawford Long get credit for developing anesthesia, or Thomas Morton, william Thomas Morton, but that debate will go on, but I'm sure Mass General will take credit for it. So, anyhow, that's just one example. So give us another example of something that may be more akin to what you do day to day, where there's a discovery that leads to some sort of innovation.

Speaker 3:

Well, I mean the basic ones that we talk about, you know, opium we have the opium. You know the opioid epidemic but opium we actually use morphine. Morphine we use daily.

Speaker 2:

There is good example, something that comes from a plant that you kind of figured over the years how to use it.

Speaker 3:

So it also gets you high. Also good for pain, but we have no involved to a drug. But no, we still have the opioid epidemic that we have to deal with. We also have taxal, which is from a tree and that is actually used for breast cancer. And, interestingly enough, it was being used in South America to treat breast cancer as a as a herb, Really yeah. And there was a doctor working there who got breast cancer and in doing her research she actually used it as well as her own chemotherapy.

Speaker 2:

Is that right?

Speaker 3:

That's crazy Interesting, but that's actually and we use that today as one of the basic drugs for breast cancer. I think I've talked to Dr Coran before about a drug. Well, it's not. It's an herb that we use in the islands for wound therapy and, working in Jamaica, we unfortunately run out of drugs a lot in our public hospitals and what we found, that Papine, which is from Papaya we prepared a certain way and we put it on diabetic wounds and, while I didn't do a protocol or publish, by actually treating a lot of wounds and controlling their sugar better, we decreased amputations by more than 75%.

Speaker 2:

That's crazy. So that would be called an observational experiment, which is, you know, the first level of coming up with an idea and developing the idea, and then you need to go from that observational experiment to a randomized experiment. We talk a lot about that in MedEvidence is that many observations will turn out to be valid but some won't, and the only way you figure out what's valid and what may be less effective is by doing a randomized study. I'm going to talk more about that process, but that's a tremendous example of it. Another example of it, I guess, would be development of aspirin.

Speaker 3:

Willow bark tree.

Speaker 2:

Yeah you got a willow bark tree, and so that was actually known in antiquity to be a cure for headaches by just sleeping under a willow tree. And of course it was synthesized, I guess, by the Bayer company in Germany. At some point they actually figured out what the active ingredient is in that willow bark that took away your headache. And of course, here you have aspirin, and you know to this day we do randomized clinical trials to see how well aspirin works. And what's crazy about it is that we know a lot about aspirin but there's a lot that we still don't know, like what the best dose is for different reasons. What's the best dose to prevent a stroke? What's the best dose to use with other agents prevent your heart arteries from getting clogged up again after a stents placed? So interestingly, even something from antiquity that was first discovered based on observation that now is established as a good medical intervention, still has lots of questions around exactly how to use it.

Speaker 3:

True.

Speaker 2:

So in our next episode we're going to talk how we go from that observational stage to truly understanding how to dose products and in what patients use them in the real world.

Speaker 1:

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