This Podcast Will Kill YouThat little bottle of retinol serum sitting on your bathroom counter - what do you know about its history? This week, we’re digging deep into the man behind the medicine, renowned dermatologist Dr. Albert Kligman, and the unethical research he conducted at Holmesburg Prison in the mid-20th century. Kligman’s research program at Holmesburg spanned decades, involved dozens of experiments (including tretinoin) and thousands of individuals, received ample funding from public universities and many pharmaceutical companies, and was generally praised until it all came crashing down in the early 1970s. But, as we’ll discover, the unethical behavior persisted even after the program’s closure as Kligman fought to get tretinoin to market. The murky history of retinoids might be a bit too long to include on the label, but this episode forces us to consider the human cost of a household product and the importance of acknowledging that history.
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In nineteen seventy and nineteen seventy one, I participated in three different types of tests. Two of them, nicknamed the patch tests by inmates, dealt with the experimentation of new products not yet released to the general public. The first patch test was one that tested lotions, creams, skin moisturizers, and suntan products. The procedure for these tests was as follows. A grid made from thick strips of white hospital tape was fixed to the upper portion of an inmate's back shoulders. The grid consisted of about twenty squares. In each of these squares, a dab of lotion was applied and the inmate's back was exposed to different temperatures from a sunlamp. The exposure to the sun lamp lasted anywhere from fifteen to thirty minutes, after which each square was inspected for degree of blistering or other adverse reactions. The grid was then covered with a large solid piece of tape to prevent tampering by the inmate, and the inmate was returned to his cell. This test lasted about thirty days, and once a day the the inmate was called back over to the lab and exposed to the sun lamp. After about five days of the sun lamp, there were sections of the skin that were burnt a deep brown and the skin started to peel, itch and blister. If a certain square became too damaged, it was covered over with a permanent piece of tape and the test continued.
On the grid.
That sounds awful erin Yeah, it really, it really really is. And so that was from William Robb, who was at one point in Holmesburg Prison and participated in these experiments that will make up a big focus of today's episode. And that ultimately was from a book titled Acres of Skin by Alan Hornblum.
Hi, I'm Aaron Welsh and I'm Eron Auman Updike.
And this is this podcast will kill You.
And today's episode we are covering one half of a big story all about retinoids.
Yeah.
You know, sometimes with the topics that we choose, you never know where you're going to end up and what most story is going to be. Yeah, and this was certainly the case for retinoids.
And you know, we.
Decided to do that because we were just like, what's the deal with retinoids? Yeah, and looking into the history of things like retina I found a darker story than I anticipated, and the story itself both like the origin of retina and the marketing of you know, retinoids in general, that is one half of this big story. But I also wanted to tell the story of the experiments at Holmesburg Prison from the nineteen fifties to the nineteen seventies because it's not a very commonly told story of a really dark chapter in American medical history.
Also, I don't think I realized that this story is going to take place in the nineteen fifties to nineteen seventies. That's like just very depressing, Aaron, Like.
How recent?
How recent?
I mean what Tuskegee was whistleblown in the early nineteen.
Seventies, I know, Yeah, I know, I know. And then yes, so that is.
What this episode is going to focus, all on the history how did retine get to market and a little bit more about one of the guys who brought it there. Yeah, and then the second episode, which will be your focus erin is do retinoids work?
Right, It's gonna be more light hearted episode than this one. So next week we'll get into what retinoids are, how they work, do they work, what do we use them for.
And a big.
Part what I'm most excited about in that episode will be what's the difference between and over the counter retinoid and the stuff you get my prescription? And is there one?
I am? I'm very excited for that because the amount of claims that I see both on product but also just on the internet in social media and whatnot for the magical powers of retinol. I want to know, like, are there magical powers it is?
I mean, it's a supplement's episode two point Oh oh, can't wait for It's gonna be so fun.
But first, but first we have quarantini dime, we sure do.
What are we drinking this week?
Aren arin?
This week we could drink only skin deep skin deep ye.
And in skin deep appropriately is carrot juice because retinoids are derived from vitamin A ultimately, which is found in great quantities and carrots.
Yeah, it's beta carotene, which is like will convert into vitamin A in your body. It's a long.
Story technically speaking.
And it also has ginger and lemon juice and some simple syrup and some vodka and it's a tasty little concoction.
I might have to play around with the ratios a little bit, but.
It's gonna be fantastic. You can find the full recipe for that quarantini and the very healthy and non alcoholic Plosi Burita on our website This Podcast will kill You dot com and on all of our social media channels too.
On our website This Podcast will Kill You dot Com. There's a lot of things that you can find. You can find the sources for each and every one of our episodes. You can find transcripts. You can find links to our bookshop dot org, affiliate account, links to our Goodreads list, links to music by Bloodmobile, links to merch links to Patreon. There's a contact us form where you can say like, hey, do this episode or hey, uh, come talk at our university whatever it is. There's also a submit your first hand account form.
You know it's good safe, check it out.
Check it out, and if you haven't already, be sure to check your podcatcher and make sure that you're subscribed to this podcast, which really helps us. And if you haven't already left us review, we would sure love it if you did. Okay, should we get started, Yes, please tell me erin all about how Retine came to be.
All right, it's a long story, so let's take a quick break before we begin. How many of you out there listening has in their bathroom cabinet a little bottle of serum or a little tube containing retinol or retinoids.
Too? I have two, I have one.
Two different kinds.
And how many of you have been prescribed retinee in the past? And you know if it's the end of two here one, two of two. But I'm guessing that it is a.
Lot of you out there.
I haven't used my retinal in a long time because it makes me break out. But I bought it because I had heard on like commercials, or on tiktoks, or like the skincare addiction subreddit that it was great for your skin, for preventing fine lines, reducing the signs of aging, like all of those things. But beyond the question of does it actually do those things is a deeper question whose answer reveals the surprisingly dark history behind this ubiquitous skincare component. How did we learn about these effects of retinoids on the skin in the first place? Lurking beneath these claims of anti aging, poor cleansing, and acne prevention claims which I know next week you're going to talk about like which is their support for, which isn't their support for? But behind all of those claims is a grim history involving human experimentation on incarcerated individuals, experiments so profoundly unethical that they were described as a violation of the Nuremberg Code, you know, like the code that was developed in nineteen forty seven in response to Nazi doctor war trials.
Ooh, Warren, that's not How have we never heard of this?
I don't know, because it is commonly mentioned alongside Tuskegee syphilis study, alongside the Willowbrook State Schools, alongside the birth control pill experiments in Puerto Rico, Like, it's all sort of part of it. I had never heard about this though in medical ethics class. But maybe it was just a long ago that I had forgotten.
Yeah, or maybe it was just glossed over us, like the history prison and like yeah not not no detail or something.
Right, still people devaluing human life because.
Of yeah, yeah, yeah, okay, I want to learn, right, Okay, So what were these experiments for?
How were they allowed to happen? And who brought them to light? So that's the story. That I'm going to tell today, and it's not the history of retinoids that you're likely to find on a skincare company website, And to be fair, retinoids are just one part of the story. But I wanted to focus on it today because I think it's a crucial part of the history of medical ethics, and it's one that, yeah, you don't hear about that often.
How do highly.
Educated and credentialed individuals get to a point where they feel like they're above the rules, where they lose any self awareness that would allow them to see that they aren't nobly championing science, but in fact committing atrocities against humans. At the heart of this story is Albert Kligman, an American dermatologist who has been credited with transforming the field of dermatology from a little acknowledged subspecialty to a full on giant of industry by the end of the twentieth century. As the co inventor of retinee and an advocate for its off label uses, Kligman saw the incredible commercial potential of dermatology in terms of pharmaceuticals and cosmetics. Cosmaceuticals, but that is certainly not his only claim to fame. For more than two decades. Between nineteen fifty one and nineteen seventy four, Kligman headed a medical research program at Holmesburg Prison in Pennsylvania, where he conducted dozens of non therapeutic experiments on incarcerated individuals, the majority of which were black. Experiments ranged from assessing the efficacy of certain deodorants to quantifying the impacts of dioxin exposure. Dioxin, if you haven't heard of it before, is a highly carcinogenic substance, like it's sometimes called the most carcinogenic substance known. It's the stuff an agent orange that makes it super toxic to humans.
So he tested an on humans.
What mm hm And although most experiments didn't specify like which race he was looking for, you know, this is a call for white people, this is a call for black people. The riskiest ones were reserved for black individuals only. And this is where Retine was born, at Holmesburg Prison.
But I'm already so mad, Aaron, I don't.
Think he's just ei. There's so many more pages being angry.
My face is going to be like that talking about when it wrinkles, like I'm gonna have one.
The brow is going to be too deep for retinoids to penetrate.
This podcast does give me one of those constantly.
This podcast will give you a froid brow, give you a brow dot com worth it.
Yep.
But before we get into this the backstory of retine, let's first explore how Kligman found Holmsburg, or rather how it found him. Kligman's path to dermatology was not a straight line. He started off by first getting his PhD in botany, studying fungi. At the time, mycology was lumped in with botany or like under the botany umbrella. And then he went to medical school with a specialization in dermatology so he could keep pursuing his interest in fungi like those that cause athletes foot a lot of like you know, topical conjections.
Yeah.
A few years after graduating with his MD, Kligman, who was faculty at the University of Pennsylvania, he received a phone call from the pharmacist at Holmsburg Prison. The prison was dealing with a huge athletes foot problem, which is common in large residential facilities, and the pharmacist was at his wits end trying to find an effective treatment. And in his searches he had stumbled upon a research article written by Kligman about athletes foot and so he called the doctor for advice. Kligman was like, all right, I'm going to see this for myself. So he went to the prison to scope out the situation. And when he got there, he didn't see an athlete's foot problem, or he didn't see that alone. But what he saw instead was limitless potential.
Quote. All I saw.
Before me were acres of skin. It was like a farmer seeing a fertile field for the first time.
End quote.
Sorry, you go to a prison, see untold numbers of incarcerated individual human beings, and all you see are acres of skin.
Acres of skin. Cool?
H Great?
So that stand up guy, I.
Think gives you a little bit of a sense for where his sense of morality was when it came to experiments on right humans.
I mean, it's a lot easier to do stuff if you're just doing it on skin. Right, It's just skin. It's devoid of humanity.
I mean, and I think we'll get into this a little bit more later, but I think he did see beyond skin. But I think that what he saw was he was a little bit of the savior right Like he was like, Oh, but I am giving them freedom from boredom, I'm giving them money, I'm giving them an opportunity to learn. I'm giving them an opportunity to give back, Like this is a whole yeah, yeah, And so this acres of Skin comment is the title of the book that where most of this information that I got for today's episode comes from. It's a great book. It's by Alan Hornblum. It's one of the classic exposes of unethical human expert imitation in the US. In Kligman's eyes, Holmesburg Prison represented a near perfect study environment, and that's an opportunity that rarely, if ever comes along in medicine in an institutionalized setting. Holmesburg was not Kligman's first foray, by the way, into institutionalized settings. He also went into schools. But in all of these institutionalized settings, you could control every variable, down to how much sleep your test subjects got, what they ate, how much they ate when they ate, how much sun they got, when they could shower, how often they could shower.
All of these things.
You could have complete control over. Plus it was cheap to have someone in role in the types of trials that he was interested in trying out and testing. You would have to pay someone who was not in prison lots and lots of money to keep them going to be willing to do these things. By comparison, Holmesburg was very cheap, and so Kligman wasted no time in setting up shop at the prison.
Quote.
I began to go to the prison regularly, although I had no authorization. It was years before the authorities knew that I was conducting various studies on prisoner volunteers. Things were simpler then. Informed consent was unheard of. No one asked me what I was doing. It was a wonderful time end quote. I know, I just can't like, I can believe.
It was a wonderful time.
It was a informed consent didn't exist. It was a wonderful time.
Yeah.
Those two sentences cannot go together.
Yeah.
And I think the other remarkable thing about this is that so I'm not sure like when that quote was pulled from but it was later, like years later.
Right, It's it's obviously him looking back on his time doing this, being like this. It was so great, wasn't it.
Yeah? Cool?
You know, and he wasn't entirely wrong about things being simpler. Then it seems that from my understanding, Kligman didn't do anything technically illegal while conducting experiments at Holmesburg.
Well, I was just trying to remember at what point actually IRBs became a thing clearly after this.
Yeah, I don't remember either. I know that Tuskegee in the early seventies kind of was one of the biggest wake up calls for you know, he.
Just slipped it right in there, we need more regulation.
Yeah. Yeah, But it doesn't mean that Kligman's experiments were ethical. It just means that the laws were simply inadequate at the time. In the mid twentieth century, non therapeutic medical experiments on institutionalized populations were normalized. They really were, especially on individuals and prisons, who were seen as expendable and also as needing to quote unquote give back to society. Prisons were a real popular spot for phase one clinical trials, which were intended to test the safety of a drug, not necessarily its efficacy. And so I've talked about several of these infamous unethical experiments on the podcast before, and even mentioned them earlier in this episode. You know there's intentionally infecting children with hepatitis at Willowbrook State School on Staten Island, New York. There's, of course, said it a million times a famous Tuskegee syphilis experiment. Just a few episodes ago, I talked about how incarcerated quote unquote volunteers were given a slurry containing neurovirus intended to study the effects of infection.
Yep.
And there are so many more examples out there, examples that the Nazi doctors being tried at Nuremberg pointed out in their defense in the late nineteen forties, like, hey, you guys do this too in the US.
You do this all the time.
But the American doctors conducting these experiments saw themselves as different, nothing like the Nazis, but no global warriors, doing what needed to be done in the name of science and giving their test subjects meaning quote from Kligman, okay quote, many of the prisoners, for the first time in their lives find themselves in the role of important human beings. We say to them, you're important, We need you. Once this is established, these guys will knock their brains out to please you. If the experiment does not pan out, they get depressed, they become emotionally involved in the project. The capacity to respond to love is greater than most people realize. I feel almost like a scoundrel like Machiavelli because of what I can do to them.
End quote. Oh my god, Aaron, I know this guy is Okay. I didn't read any history papers, but this guy is mentioned in the textbooks and things like that. Not like this.
Right, he is hailed as a modern father of dermatology.
Yeah, and they'll be like, oh, and the experiments that he'd had questionable ethics. This is like he is very aware of what he is.
Doing, right, he is you you know that someone like you said that to a resort that yeah, like or you wrote that like you You didn't say that like at a dinner party with like just your derm friends.
Right.
This isn't a private diary, dear diary. I feel like Machiavelli. This is like a brag.
It's like basically the equivalent of a tweet back in the day.
Exactly.
You can't take you back, No, it's it's there. And I think what's like. Kligman is one of the individuals that is often put forth as an example, and there were some medical ethicists who at the time spoke against these experiments, but for the most part, conducting research on institutionalized or vulnerable populations was widely accepted, even outside of medicine. Right that sentiment that he expressed, maybe minus the Machiavelli part, but the whole giving meaning, feeling important, giving back all of these things that was in the popular narrative about these experiments. So, starting in the mid nineteen fifties, for example, Life Magazine ran several stories on Kligman and his experiments at Holmesburg, with titles like quote Prisoner's Volunteer to Save Lives and Prisoner's Aid Medical Research seventy five percent here act as medical guinea pigs or the poison Ivy Picker of Penny Pack Park, which that last article detailed Kligman's quest to find a vaccine for poison ivy, not mentioning the not so mild side effects of the alleged vaccine, which caused a drop in blood pressure that made many people pass out and also just like having to have poison im oils rubbed all over your skin. In a nineteen sixty six newspaper article, Kligman did acknowledge to some degree the moral issues inherent in his research. Quote we had an ethical problem. How much right do you have to cause risk to a prisoner in medical tests from which he has no direct benefit?
End quote?
Seems like a rhetorical question. I don't think he answered it.
In that same article, the superintendent of Holmesburg reassured readers that quote, we will not approve anything which, on the face of it, would be deleterious to the physical well being of an individual end quote. And that sounds great like nice sentiment. But who actually has the power to say whether something is deleterious or not? It was largely up to one man, Albert Kligman. Let me be clear, though, the experiments at Holmesburg Prison are not the work of one mad scientist given to my power. This was a coordinated effort with many major players involved and ample oversight. Pharmaceutical companies like Pfizer, Hoffman, Laroche, Park, Davis Abbott all hired researchers to conduct experiments at Holmesburg. Others partnered directly with Kligman for years, and this was a University of Pennsylvania project. Nor was Holmesburg Prison the only place where medical research was unethically conducted, or the University of Pennsylvania the only institution that sponsored it. I'm not defending this experimentation in any capacity. I just want to put it in historical context, like this is not a one.
Off this which obviously just makes it that much worse. It makes it that much for everyone and everywhere.
Right, this is just one that got more attention because there's a full fledged book about it. There are plenty more that could be that are book worthy, I am certain, right, And so on that note, let's get more into the medical research program.
I'm at Holmesburg Prison.
What had started out as a small program in nineteen fifty one to nineteen fifty two when he first arrived to assess the athletes foot problem, had by the early nineteen sixties become a full fledged research machine with expensive state of the art medical equipment, trailers with monitoring equipment and padded cells, and up to ninety percent of all individuals who were incarcerated at Holmesburg participating in experiments. So there were times when ninety percent of all individuals at Holmesburg Prison were involved in one experiment or multiple, which was a very common oh my situation, and also like not to mention how being involved in multiple different trials just scientifically is not great.
Not great.
Between nineteen sixty two and nineteen sixty six, only four years, one hundred and ninety three studies were conducted at Holmesburg, including one hundred and fifty fifty three experimental drugs and then more drugs that needed marketing permission and drugs whose new uses were tested, so some of these were purely experimental.
Most of these oh wow.
The types of experiments were wide ranging, as were the financial incentives. To test hand creams you could earn a dollar a day, foot powders and deodorants testing could get you one hundred dollars a month. One hundred and fifty bucks could be yours if you were willing to have your finger numbed with novacane and then your fingernail removed to see.
How it would heal. Okay, yep.
Other experiments included sticking your arm in a sodium laurel sulfate solution for one hour each day for fifty five days in a row, testing the relationship between chocolate and acne, walking around with steel cups drapped to your forehead to collect skin cells and perspiration testing anti dandriff shampoo that oops major hair fallout, slicing skin on back to try to induce a chiloid, Implanting different kinds of gauze or even tissue from a cadaver to just look at healing and heat and like creams to help your skin heal. Applying enormous amounts of fungi to the feet, and being forced to keep your boots on continually for a week, even overnight to see how bad ringworm infection could get. The riskier the test, the higher the potential reward, like you could get one thousand to fifteen hundred bucks to test out eye drops or hallucinogenic medications, pills that were meant to speed up sun tanning but gave people violent GI symptoms, Infecting people with pathogens like Staph aureus, candada albacans, herpes virus, influenza tests that involved liver biopsies and nearly killed seven inmates. I don't know why the liver biopsies were needed.
Why are you doing liver biopsies and what?
Yep, okay, don't know.
Radioactive isotope testing exposing people to dioxin and observing the results.
It's like, what happens? What happens if we do this?
At one point, the US Army was testing psychoactive or mind controlled drugs in those padded cells. I mentioned people who used to be at the prison said that you could pick out those who were volunteers from those who weren't from their checkered backs. Like so from the first hand account how I mentioned the skin test, the patch tests. So many of those tests left physical and emotional scars, extreme sunburns leading to skin discoloration, incisions where the gauze was inserted and never quite fully healed, biopsy marks. And then you have, like the from the mind control or psychoactive drugs, you had flash People would experience flashbacks or bad trips years later, personality changes. But what choice did People will truly have other jobs at Holmesburg Prison, like making shoes, knitting socks and shirts, sewing pants, plumbing. You would get fifteen cents a day, It's no contest. Put some lotion on your hands. A dollar a day, sure, eyedrops. If you need to send money back home, yeah, I need to do this. How much choice is there? And those that were involved in the experiments would often get better treatment, better food, and higher social standing in addition to that substantial financial incentive. And a dark side of this that was kind of came out later on was that the financial disparity between people who participated in the trials and those who didn't sometimes led to coercion and sexual abuse. The researchers did not mention the health risks involved in any experiment, or even what the experiment was testing. None of the people who participated remember ever hearing the words informed consent.
Right.
I mean, even Kligman himself was like, right, didn't exit, itn't exist. We didn't do that.
They remembered signing release forms, but the forms didn't have any additional information on them. As the author of Acres of Skin, Alan Hornblum puts it, quote, a drowning person does not ask penetrating questions about a life raft end quote. Even if they had asked questions, would they have gotten honest answers. With the large scale of the research program at Holmsburg, Kligman couldn't have expected to fly entirely under the radar. Even if he were a careful and detail oriented researcher, which he was, not he ended trials prematurely. There was a lot of evidence of falsified data. He had, like I said earlier, people participating in multiple trials like overlapping, that were testing different things. He was just kind of like, Oh, this looks like it's not where I'm going.
We're ending the trial.
Oh, this looks like where it's where I wanted to go. We're ending the trial, and saying that this is exactly.
What I wanted to find.
And so, sure enough, red flags were thrown up as early as the nineteen sixties, which is when it came to light that Kligmann was testing DMSO on humans, which was a solvent banned from human testing.
By the FDA.
Like at that point it had already been banned, and so as a result, Francis Kelsey, who you may remember from our solidamide episode as the person who was largely responsible for preventing the litamite from being marketed in the NAUS, she led the charge to disqualify Kligmann from testing new drugs. It ended up being temporary, his disqualification, much to the relief of the many pharmaceutical companies who loved the Holmesburg prison as a cheap way to try out medications, and he had a lot of other, like you know, eminent dermatologists who wrote in on his behalf like this is unprecedented. He has done nothing but good for the dermatology community.
Blah blah blah.
This is a this is out of hand. You need to let him do the work that he was put here on this earth to do.
Oh wow, yeah, that kind of thing.
But even though Kligman's disqualification was reversed, the tides had begun to turn, not just for Kligmann but for research on institutionalized populations in general. Revelations about the Tuskegee Syphlis experiment came to light in nineteen seventy two, which marked a big shift in attitudes towards medical experiments on vulnerable populations and what informed consent truly means? Can there be such a thing in prisons? In schools? Can there be such a thing? What does voluntary mean? How can you tell if someone is volunteering or if there is coercion? And this is still very much an ongoing discussion in medical ethics. Is it depriving people of an opportunity to earn money? Is it something that like, well, then you're not giving them the right to make decisions on their own behalf. But also, how are those decisions influenced by the power dynamics, by the structure of the.
Power structure and the dynamics. Is it's very difficult to overcome, it is, Yeah.
And all of these conversations really seemed to ramp up, of course, in the early nineteen seventies, as more and more of these experiments in institutions came to light. Kligman, for his part, never seemed to acknowledge that what he did was an ethical that he exploited a vulnerable population. He saw the work he did as quote unquote quite beneficial to all.
In his mind.
He gave these individual skills a reprieve from boredom, money, sure, but also excitement and a purpose. And when the medical experimentation program at Holmesburg was forced to close in nineteen seventy four, he ran against its closure quote A very good case of the triumph of the do gooders. All we did is offer them money for a little piece of their skin end quote.
All these do goods go the gooters. How dare you be a do good doctor, ma'am?
I know right?
Like, where does this fit into under your hippocratic oath.
This doctor is not supposed to be a do gooder, who is man.
And that's what's so, that's what's the mental gymnastics where he did think he was doing good. Right, this is beneficial to all. I don't think that he would ever admit that he violated the hippocratic oath. Right right, no harm because he did so much good, like the net was good.
It's like the train and the one person versus the train and the blah blah blah.
Yeah, get real, dude, Yeah, get get real, dude. The medical experimentation program at Holmesburg did not go quietly into the night. There was denial of any wrongdoing. There was bargaining that if they improved things, could they still experiment. There was outrage, basically all the stages of grief, minus perhaps acceptance. Kligman had always seen himself as a maverick. He told his students that rules don't apply to genius, that they just get in the way of creative minds. Yeah, no one could tell him that what he did was wrong and have him actually believe it or acknowledge it. Even when the lawsuits came out, which were dismissed because of statute of limitations.
Oh God.
I think there was eventually some settling outside of court, although I don't remember the details of it. But even when sweeping changes were made to guidelines for obtaining informed consent in medical research and research on vulnerable populations, I still couldn't admit that what he did was wrong. Even when his research at Holmsburg was deemed to be in violation of the Nuremberg Code. He seemed to think that the ends justified the means.
Wow, but what exactly were those ends?
Right? Was it the advancement of science, Was it relieving people suffering? Or was it simply making.
Money, making a buck? That's my guest, Aaron.
You know, I can't say for certain because I don't know him in his head, but given his words and actions after Holmesburg, I think that it's pretty clear that money was at least a strong motivating factor. And that brings me finally to the story of retinee. Retinoids, which include retinol and retinee, which is the brand name of Trettonoen, are all derivatives of vitamin A, and someday we'll probably do an episode just about vitamin A.
For sure, because we're focusing on and like topical retinoidstadata, vitamin as is its own thing.
There's any of the same thing, But there's definitely plenty more to the story of vitamin A. Yeah, And so the short story that I'll tell right now is that people have used vitamin A for likely thousands of years to treat night blindness. Beginning in the twentieth century, people grew interested in the other properties of vitamin A and other vitamins. It was like that vitamin A day revolution that I've talked about many times. And one of the things that they noticed was that vitamin A seemed like it might be effective in treating acne. In the nineteen forties, a researcher named Jonathan Stroumfjord dosed patients with one hundred thousand international units of vitamin A every day for a minimum of six months injections, right, I think so, yeah, And the results were striking. Seventy nine patients were completely cured and only three showed no improvement. That's like pretty pretty strong, yeahs. Later studies conducted in nineteen sixty two by doctor Beer and doctor Stutgen used vitamin A acid which I'm assuming is Trettonoen.
I'm not sure.
I don't know if it went by the name. Then this was administered orally, and they found similar benefits.
All of these.
Researchers noted the extreme skin irritation in the early weeks of treatment, and one researcher was like, I don't want to do any more of these studies because I am so alarmed at the strength of this reaction. This can't be good for people. But that didn't bother Albert Kligman when a UPenn medical resident tried out the vitamin A derivative at Holmsburg after reading Beer and Stuttgen's paper quote, doctor Kligmann saw that it irritated the skin and asked if he could work with it end quote. So he like saw the irritation and was like, ooh, green flag right, like.
Oh, this means it's doing things.
This means it's doing things.
By nineteen sixty three, Kligmann had set up human trials at Holmsburg exploring the potential uses of the medication, which he received free of charge from Hoffman Laroche, who of course saw its commercial potential.
At the prison, Kligman sought.
To find the right dose, the right delivery system like orally or topically, and the right chemical composition of the vitamin on the backs and faces of the individuals.
At Holmsburg.
He's quoted as saying that early on he experimented with quote unquote very high doses of vitamin A. Quote I near killed people before I could see a real benefit. Every one of them got sick.
End quote.
Ah Okay, this kind of just keeps getting worse there, and he keeps.
Getting I know, you're like, surely there's not more to this.
Oh, trust me, there is. Yeah. Yeah.
He used doses of one percent vitamin A acid trettonoen, which is one one hundred times stronger than the point one percent that it became later.
On one percent. Yeah, oh my, yeah, that's way too strong.
Uh.
And unsurprisingly that strong of a dose caused intense irritation to the skin, but that that didn't worry Kligmann in the slightest. In fact, he took it as a good sign, an indication that this drug was working. This trait of his to keep pushing push past any obstacle. It earned him the admiration of some like a former student who said that he quote thought retine would never sell. It caused a severe reaction in patience. Their faces became quite red and irritated. But Kligmann has the capacity to push when others won't. He could see the value of retine as possible therapy. Time has shown that it has positive results. It's a fantastic drug. He's a genius end quote. Okay, And there's no denying that has been incredibly valuable for many people. But I think it's important to remember that it wasn't Kligman dealing with the irritation. He wasn't pushing himself. He was just pushing other people who had no say in the matter. More than dioxin, more than radioactive isotopes, more than the mind controlled drugs. It was vitamin a acid trettonoen that fascinated Kligman the most, and he would be rewarded handsomely for it. After switching allegiance from Hoffman Laroche to Johnson and Johnson, Kligman helped bring retine to the market where it first became available in nineteen seventy one. The timing for Kligman could.
Not have been better.
The research program at Holmsburg was winding down. It would fully close in nineteen seventy four, and Kligman was eager to leave that world behind to explore the realm of cosmaceuticals.
The immediate success.
Of retine gave Kligman the opportunity to think about not just how to study these drugs, but how to market them. He believed that retinee held promise beyond just treating acne, that it could also reduce signs of aging. Kligman, although a lot of literature would have you believe otherwise, didn't come up with this on his own. His patients did. They told him that after a course of retinee, their skin looked younger, they had fewer wrinkles, it seemed to be brighter. Kligman didn't believe them initially. Quote I have always told students that if you start to believe your patients, you're going to end up as a quack. I have a doctrine, don't believe patients. So I was a victim of my doctrine.
End quote.
Aaron, these quotes that cannot be real. I know.
I'm like, this is a caricature of what the worst like. Did he ever study hysteria? I can only imagine, Right, I.
Have a doctor and don't believe patients. Oh my, this guy is so celebrated.
I cannot I know, don't believe patients. If you believe your patients, you're a quack, told students, like he trained students, right.
Yeah, I'm not trained in dermatology, so I am only knowing when I'm reading on papers. So I don't know how much they like him in dermatology circles, but like, I hope they don't.
What yeah, yep, so there you go.
Cool, cool, cool yep.
I don't know what made him decide to eventually believe at least these patients, but in the early nineteen eighties he began running experiments to see whether their claims had any basis. This time he used animal models, it seems, but the reported results were remarkable. A complete transformation, Retinee could be the most powerful anti aging drug to hit the market. According to Kligman, there was just one problem, and it was a big one. Retinee was approved by the FDA to treat acne, not as an anti aging product. To sell it as an anti aging product, Ortho, a subsidiary of Johnson and Johnson that made retine would have to get FDA approval for this new use, which meant going through all those steps that would take years and lots of resources with no guarantee of success. And so Kligman proposed a workaround, a propaganda campaign using Ortho sponsored conferences, paid for doctors, ads in medical journals, articles in medical journals, features in fashion magazines, and testimonials on TV programs to promote the anti aging, anti wrinkle properties of retinee. The campaign was a major success. In nineteen eighty seven, the year before they started spreading the propaganda, six percent of retine sales were for off label uses. The following year it shot up to sixty five percent. Okay, sales grew to around one and a half million dollars each day, which is ten times higher than it had been before the campaign. Kligman, for his part, was getting paid by Ortho for his work as a consultant and enjoying his share of the royalties. This massive change in revenue stream and in off label uses, of course, drew the attention again of the FDA. It was legal for physicians to prescribe off label usage of retine for their patients. Like if someone came in and was like, I want to try this out as an anti wrinkle cream.
Can you prescribe this for me? Okay, I'm going to use it in.
This way, but it was illegal for a company to promote such off label usage. F began an investigation into Ortho for off label marketing, and this caught the attention of the popular media, who saw the situation as the latest example of the sneaky doings of the pharmaceutical industry. An article about retine in Money magazine pointed out the following, it's a hefty list, but I like it because it just have any of these things changed. Number one the pharmaceutical industries increasing propensity to bypass clinical physicians and promote new prescription drugs directly to consumers through the popular press.
I mean every single ad on a Hulu yep.
Number two, major corporate publicity of medical researchers who abandoned objectivity for corporate dollars on behalf of new products and lavish pr campaigns.
Every single dermatologist and researcher who has their own skincare line now yep, yep.
Number three, the extremely close relationships between pharmaceutical companies and doctors.
Weirdly, especially true in dermatology, like very I mean there's supposed to be more things in place for that, yeah than there are.
Number four the shallow perusal by the general press of pharmaceutical company press releases in the quest for bold headlines.
Hi.
Yeah.
Number five the FDA's underfunded, understaffed administrative situation in the face of well organized corporate initiatives and sophisticated publicity techniques.
Imagine if we funded organizations that are supposed to protect the public.
What a concept.
Sorry, this was written yesterday or ID know, right, nineteen eighty eight, I believe, Yeah, yeah, so that is just have things changed.
I don't think so.
No, But all of this bad press was not ideal for ORTHO, and things were only going to get worse because the University of Pennsylvania had caught wind of what was going on and sued Kligman for filing a personal patent for this new anti aging retine called Renova, effectively cutting out UPEN and keeping all the profits between Kligman and Johnson and Johnson.
So sorry. But also because when you said that they sued him, I got really excited, like they knew he did something wrong. But no, it's just because they weren't going to make any money.
Off.
You've let us out. Oh goodness me.
The case was ultimately settled out of court with to presumably everyone's satisfaction, but ORTHO still had the FDA to contend with, and they were panicking. ORTHO ordered employees to start shredding documents, destroying videotapes, hiding any evidence at their personal at their employees' houses that they had entirely orchestrated. This plan to market retine for off label uses was a shredfest.
I'm not kidding. Isn't this wild?
They really thought that was gonna work, though, I know, I.
Know, right every time.
I don't know how they thought they weren't going to get caught. It doesn't make sense.
And they definitely got caught.
Yeah.
In nineteen ninety two, the US government filed criminal charges against Johnson and Johnson, but a lot of the requested documents that were in those charges had been destroyed, so they were also charged with destroying documents. The trial went on for two years, and corporate officials were very aware that every day that the trial went on, the release of retine as an anti wrinkle medication was delayed, and so in January nineteen ninety five, they pled guilty to unlawfully promoting retine for photoaid and for other unapproved indications. To the question of did ORTHO knowingly and correctly persuade and attempt to persuade the employees to destroy, mutilate, and conceal documents and other objects, they said yes. They also answered yes to did Ortho persuade employees to destroy those documents quote with the intention to impair the integrity and availability of those documents and objects for use in an official proceeding end quote? Their guilty plea brought them a hefty fine, a total of seven and a half million dollars, which is one of the largest ever paid for.
An FDA violation. Wow at the time.
Yeah, but to Ortho, to Johnson and Johnson, it may have well have been pocket change, right, like they had actually.
Competed to what they're about to make, Like exactly.
They had already made millions, untold millions on off label well on retinee sales in general, but off label uses, and they were about to make a whole lot more with Renova. A month after the decision, the FDA approved Renova for sale with a caveat on a label quote. Renova does not eliminate wrinkles, repair sun damaged skin, reverse photoaging, or restore a more youthful or younger dermal histologic pattern.
End quote.
Sorry, so it was proved to treat photoaging, but they had to say that it doesn't treat.
Doesn't reverse photoaging.
Yeah, okay, yeah, histologically histologically okay, I don't know what the standard for we'll get you know, evidence was, I guess.
Yep.
But it didn't really seem to make a difference in sales, right, or at least like I don't know if it did having that caveat on there, Because for every skin care product that promises eternal youthfulness and a wrinkle free life, you'll find diehard supporters, you'll find clinically supported claims.
And you'll find it next to impossible to actually.
Get to the bottom of whether or not a product works as it's supposed to, all because of the vast sums of money to be made obscuring the truth. And I know that that's like a very cynical take, and I'm sure that there are products out there that work or that work for some people, which is why I'm really excited for next week's episode, where you'll tell me all about the actual data on tretnoen and retinol and all of the rest of the retinoids. But before I finally wrap this up for good and tell you my short list of sources, I want to circle back to what I said at the beginning of this history section, how we don't think enough about where our knowledge comes from and who bore the cost. We know about different hepatitis viruses and had an early hepatitis B vaccine in part because of the unethical experiments performed by Saul Krugman at Willowbrook State School on Staten Island. We know how syphilis progresses untreated, in part because of the Tuski Yeesifless study, which continued even though treatment was available. We know how the birth control pill works in part because Gregory Pinkus measured its efficacy by testing it out on women in.
Puerto Rico who were never told the purpose of the pill or.
Any risks involved. We know about tretton noan as a treatment for acne and possibly for wrinkles, in part because of the unethical experiments performed by Albert Kligmant at Holmesburd Prison. I'm not saying throw out your retinol in protests, but just that I think it's so important that we remember how we came about this knowledge and all the knowledge that we have.
I feel like it's also what is so often missing from all of the discussions about the scientific achievements and advancements, like not just current ones, but ones that we don't even think that much about. I think for me, I know, it's one of my favorite parts of this podcast is learning how even though it's usually very depressing and horrific, I can always never believe that we didn't already know this, like that I didn't learn this in all of the training that I've gotten. It's just it's it's so left out of the story it.
Is, and I sometimes wonder why that is.
Like obviously, in a classroom setting, your time is limited and you need to get across this, this and this, But is it Do people think that it's a distraction, you know, so like for instance, how the Upton Sinclair's The Jungle highlighted how gross the meat was instead of the worker conditions, Like do people think that it's just going to distract from how retinoids help with acne?
I don't know.
I think it's bigger. I think it's in partant Maybe this is just me like hypothesizing too much or whatever, but I think it's also in part like the way that we always learn everything in isolation, right, Like we're so used to like, well, you have to learn your history in a history class, and like, well, you don't take a history of medicine class in med school. That's not a thing. So you're never getting that then, because you learned like what European history or like whatever history that you took in college as like a you know, general requirement that has nothing to do with the specific field that you might be in, and you never might learn the history of that field because there, I mean, there's just too much to know, the same way there's too much science to know, there's too much history to know too, so right.
Yeah, but it is that sort of like that siloed nature of education where if you learn about unethical human experiments, you're going to learn about it in a medical ethics class, right in your ethics class, right, But you're not going to learn about it in your dermatology class.
No. Also, I'm not sure that we even had it specific ethics class in med school.
I think I did in my EPI masters.
Yeah, I might have had one there, but that's a that zine problematic. Yes, certainly, we all just need to learn. We need to learn it, we need to learn more learn it.
And speaking of learning it, sources, so I pretty much just had one for this episode, which was Acres of Skin by Alan Hornblum. I also have a few other papers that I'll post that are by Kligman in case you are interested in reading, like firsthand how he wrote about some of these experiments, and it's really funny. One has at the top like this was research was sponsored by an unrestricted educational grant from Orthopharmaceuticals, which is least it's like you know, at least.
Easily disclosed and not like in the subfooting.
It's not in the very very last page after you've read it and you're like, are you kidding me? This is now like disclosure here? Uh? But yeah, So I will post all of those sources and also aarin your sources next week we'll go on the same page on our website, this podcast will Kill You dot com.
You can find the list of sources from this episode in every single one of our episodes there.
Check it out.
Thank you to Bloodmobile for providing the music for this episode and all of our episodes.
Thank you to Leona Squilacci and Tom Bryfogel for the incredible audio mixing.
And thank you to everyone at Exactly Right.
And thank you to you listeners. We hope that you enjoyed this episode and are super stoked for next week's episode, where we're going to get into what are these writtenoids anyways and what is their evidence?
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We appreciate your support so so so so very much.
Yesh, we do thank you well.
Until next time, wash your hands you.
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