November 5, 2024 • 57 mins
That 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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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Speaker 1 (00:00):
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.
(00:23):
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
(00:46):
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
(01:06):
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.
Speaker 2 (01:17):
On the grid.
Speaker 1 (02:04):
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
(02:25):
Skin by Alan Hornblum.
Speaker 3 (02:30):
Hi, I'm Aaron Welsh and I'm Eron Auman Updike.
Speaker 1 (02:33):
And this is this podcast will kill You.
Speaker 3 (02:35):
And today's episode we are covering one half of a
big story all about retinoids.
Speaker 4 (02:45):
Yeah.
Speaker 1 (02:46):
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.
Speaker 4 (02:57):
And you know, we.
Speaker 1 (02:59):
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,
(03:23):
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.
Speaker 3 (03:40):
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.
Speaker 4 (03:49):
How recent?
Speaker 3 (03:50):
How recent?
Speaker 1 (03:51):
I mean what Tuskegee was whistleblown in the early nineteen.
Speaker 4 (03:55):
Seventies, I know, Yeah, I know, I know. And then yes,
so that is.
Speaker 1 (04:01):
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?
Speaker 3 (04:16):
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.
Speaker 4 (04:26):
And a big.
Speaker 3 (04:27):
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?
Speaker 1 (04:37):
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?
Speaker 3 (04:54):
I mean, it's a supplement's episode two point Oh oh,
can't wait for It's gonna be so fun.
Speaker 1 (04:58):
But first, but first we have quarantini dime, we sure do.
Speaker 4 (05:05):
What are we drinking this week?
Speaker 2 (05:06):
Aren arin?
Speaker 3 (05:07):
This week we could drink only skin deep skin deep ye.
Speaker 1 (05:13):
And in skin deep appropriately is carrot juice because retinoids
are derived from vitamin A ultimately, which is found in
great quantities and carrots.
Speaker 3 (05:24):
Yeah, it's beta carotene, which is like will convert into
vitamin A in your body. It's a long.
Speaker 4 (05:29):
Story technically speaking.
Speaker 1 (05:33):
And it also has ginger and lemon juice and some
simple syrup and some vodka and it's a tasty little concoction.
Speaker 4 (05:41):
I might have to play around with the ratios a
little bit, but.
Speaker 3 (05:43):
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.
Speaker 1 (05:57):
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
(06:19):
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.
Speaker 4 (06:30):
You know it's good safe, check it out.
Speaker 3 (06:33):
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.
Speaker 1 (06:53):
All right, it's a long story, so let's take a
quick break before we begin. How many of you out
(07:15):
there listening has in their bathroom cabinet a little bottle
of serum or a little tube containing retinol or retinoids.
Speaker 4 (07:25):
Too? I have two, I have one.
Speaker 3 (07:29):
Two different kinds.
Speaker 1 (07:30):
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.
Speaker 4 (07:39):
Lot of you out there.
Speaker 1 (07:41):
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
(08:01):
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
(08:22):
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
(08:44):
developed in nineteen forty seven in response to Nazi doctor
war trials.
Speaker 3 (08:48):
Ooh, Warren, that's not How have we never heard of this?
Speaker 1 (08:54):
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.
Speaker 3 (09:15):
Yeah, or maybe it was just glossed over us, like
the history prison and like yeah not not no detail
or something.
Speaker 1 (09:22):
Right, still people devaluing human life because.
Speaker 3 (09:26):
Of yeah, yeah, yeah, okay, I want to learn, right, Okay,
So what were these experiments for?
Speaker 1 (09:33):
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.
Speaker 4 (09:56):
How do highly.
Speaker 1 (09:57):
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
(10:20):
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
(10:43):
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.
(11:04):
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.
Speaker 4 (11:26):
So he tested an on humans.
Speaker 1 (11:28):
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.
Speaker 3 (11:52):
But I'm already so mad, Aaron, I don't.
Speaker 4 (11:54):
Think he's just ei. There's so many more pages being angry.
Speaker 3 (11:57):
My face is going to be like that talking about
when it wrinkles, like I'm gonna have one.
Speaker 1 (12:02):
The brow is going to be too deep for retinoids
to penetrate.
Speaker 3 (12:06):
This podcast does give me one of those constantly.
Speaker 1 (12:10):
This podcast will give you a froid brow, give you
a brow dot com worth it.
Speaker 4 (12:15):
Yep.
Speaker 1 (12:16):
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
(12:38):
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.
Speaker 3 (12:51):
Yeah.
Speaker 1 (12:52):
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
(13:13):
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
(13:37):
was limitless potential.
Speaker 4 (13:39):
Quote. All I saw.
Speaker 1 (13:41):
Before me were acres of skin. It was like a
farmer seeing a fertile field for the first time.
Speaker 4 (13:48):
End quote.
Speaker 3 (13:51):
Sorry, you go to a prison, see untold numbers of
incarcerated individual human beings, and all you see are acres
of skin.
Speaker 4 (14:04):
Acres of skin. Cool?
Speaker 3 (14:06):
H Great?
Speaker 4 (14:08):
So that stand up guy, I.
Speaker 1 (14:10):
Think gives you a little bit of a sense for
where his sense of morality was when it came to
experiments on right humans.
Speaker 3 (14:18):
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.
Speaker 1 (14:24):
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
(14:45):
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
(15:09):
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,
(15:31):
what they ate, how much they ate when they ate,
how much sun they got, when they could shower, how
often they could shower.
Speaker 4 (15:39):
All of these things.
Speaker 1 (15:40):
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
(16:02):
very cheap, and so Kligman wasted no time in setting
up shop at the prison.
Speaker 4 (16:07):
Quote.
Speaker 1 (16:07):
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
(16:29):
can believe.
Speaker 4 (16:32):
It was a wonderful time.
Speaker 3 (16:33):
It was a informed consent didn't exist. It was a
wonderful time.
Speaker 4 (16:38):
Yeah.
Speaker 3 (16:39):
Those two sentences cannot go together.
Speaker 4 (16:42):
Yeah.
Speaker 1 (16:43):
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.
Speaker 3 (16:52):
Right, It's it's obviously him looking back on his time
doing this, being like this. It was so great, wasn't it.
Speaker 4 (16:58):
Yeah? Cool?
Speaker 1 (17:01):
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.
Speaker 3 (17:14):
Well, I was just trying to remember at what point
actually IRBs became a thing clearly after this.
Speaker 1 (17:21):
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.
Speaker 4 (17:30):
Just slipped it right in there, we need more regulation.
Speaker 1 (17:33):
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
(17:55):
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
(18:16):
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.
Speaker 3 (18:36):
Yep.
Speaker 1 (18:37):
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.
Speaker 4 (18:50):
You do this all the time.
Speaker 1 (18:53):
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.
(19:17):
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
(19:37):
because of what I can do to them.
Speaker 3 (19:39):
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.
Speaker 1 (19:54):
Right, he is hailed as a modern father of dermatology.
Speaker 3 (19:57):
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.
Speaker 1 (20:05):
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.
Speaker 4 (20:21):
Right.
Speaker 1 (20:21):
This isn't a private diary, dear diary. I feel like Machiavelli.
This is like a brag.
Speaker 3 (20:28):
It's like basically the equivalent of a tweet back in
the day.
Speaker 4 (20:31):
Exactly.
Speaker 1 (20:32):
You can't take you back, No, it's it's there. And
I think what's like. Kligman is one of the individuals
(20:53):
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,
(21:13):
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
(21:35):
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
(21:57):
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
(22:18):
to cause risk to a prisoner in medical tests from
which he has no direct benefit?
Speaker 2 (22:23):
End quote?
Speaker 4 (22:24):
Seems like a rhetorical question. I don't think he answered it.
Speaker 1 (22:27):
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
(22:49):
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
(23:12):
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
(23:34):
experimentation in any capacity. I just want to put it
in historical context, like this is not a one.
Speaker 3 (23:40):
Off this which obviously just makes it that much worse.
It makes it that much for everyone and everywhere.
Speaker 1 (23:46):
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.
Speaker 4 (24:00):
I'm at Holmesburg Prison.
Speaker 1 (24:02):
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
(24:24):
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
(24:45):
just scientifically is not great.
Speaker 3 (24:48):
Not great.
Speaker 1 (24:50):
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.
Speaker 4 (25:12):
Most of these oh wow.
Speaker 1 (25:14):
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.
Speaker 4 (25:34):
How it would heal. Okay, yep.
Speaker 1 (25:37):
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
(26:00):
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.
(26:25):
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,
(26:46):
herpes virus, influenza tests that involved liver biopsies and nearly
killed seven inmates. I don't know why the liver biopsies
were needed.
Speaker 3 (26:56):
Why are you doing liver biopsies and what?
Speaker 4 (27:00):
Yep, okay, don't know.
Speaker 1 (27:03):
Radioactive isotope testing exposing people to dioxin and observing the results.
Speaker 4 (27:09):
It's like, what happens? What happens if we do this?
Speaker 1 (27:12):
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,
(27:36):
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
(27:59):
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
(28:23):
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
(28:47):
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.
Speaker 3 (29:03):
Right.
Speaker 4 (29:03):
I mean, even Kligman himself was like, right, didn't exit,
itn't exist. We didn't do that.
Speaker 1 (29:09):
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
(29:31):
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,
(29:54):
this looks like it's not where I'm going.
Speaker 4 (29:56):
We're ending the trial.
Speaker 1 (29:57):
Oh, this looks like where it's where I wanted to go.
We're ending the trial, and saying that this is exactly.
Speaker 4 (30:01):
What I wanted to find.
Speaker 1 (30:03):
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.
Speaker 4 (30:16):
By the FDA.
Speaker 1 (30:17):
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
(30:41):
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.
Speaker 3 (30:59):
Blah blah blah.
Speaker 1 (31:00):
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.
Speaker 4 (31:06):
Oh wow, yeah, that kind of thing.
Speaker 1 (31:09):
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
(31:31):
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
(31:52):
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.
Speaker 3 (32:10):
Power structure and the dynamics. Is it's very difficult to overcome,
it is, Yeah.
Speaker 1 (32:17):
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.
(32:37):
He saw the work he did as quote unquote quite
beneficial to all.
Speaker 4 (32:42):
In his mind.
Speaker 1 (32:44):
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
(33:06):
we did is offer them money for a little piece
of their skin end quote.
Speaker 3 (33:12):
All these do goods go the gooters. How dare you
be a do good doctor, ma'am?
Speaker 4 (33:19):
I know right?
Speaker 1 (33:20):
Like, where does this fit into under your hippocratic oath.
Speaker 3 (33:23):
This doctor is not supposed to be a do gooder,
who is man.
Speaker 1 (33:28):
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.
Speaker 3 (33:46):
It's like the train and the one person versus the
train and the blah blah blah.
Speaker 1 (33:51):
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
(34:14):
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.
(34:36):
Even when the lawsuits came out, which were dismissed because
of statute of limitations.
Speaker 3 (34:41):
Oh God.
Speaker 1 (34:43):
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
(35:05):
violation of the Nuremberg Code. He seemed to think that
the ends justified the means.
Speaker 4 (35:11):
Wow, but what exactly were those ends?
Speaker 1 (35:15):
Right? Was it the advancement of science, Was it relieving
people suffering? Or was it simply making.
Speaker 4 (35:22):
Money, making a buck? That's my guest, Aaron.
Speaker 1 (35:26):
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
(35:47):
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.
Speaker 3 (35:58):
For sure, because we're focusing on and like topical retinoidstadata,
vitamin as is its own thing.
Speaker 1 (36:04):
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
(36:25):
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,
(36:48):
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.
Speaker 4 (37:09):
I'm not sure.
Speaker 1 (37:10):
I don't know if it went by the name. Then
this was administered orally, and they found similar benefits.
Speaker 4 (37:17):
All of these.
Speaker 1 (37:18):
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,
(37:44):
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.
Speaker 3 (37:53):
Oh, this means it's doing things.
Speaker 4 (37:55):
This means it's doing things.
Speaker 1 (37:57):
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.
Speaker 4 (38:11):
At the prison, Kligman sought.
Speaker 1 (38:13):
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.
Speaker 4 (38:23):
At Holmsburg.
Speaker 1 (38:25):
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.
Speaker 4 (38:38):
End quote.
Speaker 3 (38:40):
Ah Okay, this kind of just keeps getting worse there,
and he keeps.
Speaker 1 (38:45):
Getting I know, you're like, surely there's not more to this.
Speaker 4 (38:48):
Oh, trust me, there is. Yeah. Yeah.
Speaker 1 (38:53):
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.
Speaker 3 (39:03):
On one percent. Yeah, oh my, yeah, that's way too strong.
Speaker 4 (39:12):
Uh.
Speaker 1 (39:12):
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
(39:34):
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,
(39:58):
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
(40:20):
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.
Speaker 4 (40:39):
Not have been better.
Speaker 1 (40:40):
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.
Speaker 4 (40:51):
The immediate success.
Speaker 1 (40:52):
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
(41:13):
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,
(41:35):
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.
Speaker 4 (41:43):
End quote.
Speaker 3 (41:46):
Aaron, these quotes that cannot be real. I know.
Speaker 1 (41:52):
I'm like, this is a caricature of what the worst like.
Did he ever study hysteria? I can only imagine, Right, I.
Speaker 3 (42:00):
Have a doctor and don't believe patients. Oh my, this
guy is so celebrated.
Speaker 1 (42:09):
I cannot I know, don't believe patients. If you believe
your patients, you're a quack, told students, like he trained students, right.
Speaker 3 (42:19):
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.
Speaker 4 (42:33):
What yeah, yep, so there you go.
Speaker 3 (42:39):
Cool, cool, cool yep.
Speaker 1 (42:41):
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
(43:02):
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
(43:26):
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,
(43:47):
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
(44:09):
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
(44:30):
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.
Speaker 4 (44:50):
Can you prescribe this for me? Okay, I'm going to
use it in.
Speaker 1 (44:52):
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.
(45:13):
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.
Speaker 3 (45:35):
I mean every single ad on a Hulu yep.
Speaker 1 (45:39):
Number two, major corporate publicity of medical researchers who abandoned
objectivity for corporate dollars on behalf of new products and
lavish pr campaigns.
Speaker 3 (45:49):
Every single dermatologist and researcher who has their own skincare
line now yep, yep.
Speaker 1 (45:55):
Number three, the extremely close relationships between pharmaceutical companies and doctors.
Speaker 3 (46:00):
Weirdly, especially true in dermatology, like very I mean there's
supposed to be more things in place for that, yeah
than there are.
Speaker 1 (46:11):
Number four the shallow perusal by the general press of
pharmaceutical company press releases in the quest for bold headlines.
Speaker 4 (46:19):
Hi.
Speaker 3 (46:20):
Yeah.
Speaker 1 (46:22):
Number five the FDA's underfunded, understaffed administrative situation in the
face of well organized corporate initiatives and sophisticated publicity techniques.
Speaker 3 (46:32):
Imagine if we funded organizations that are supposed to protect
the public.
Speaker 4 (46:37):
What a concept.
Speaker 3 (46:39):
Sorry, this was written yesterday or ID know, right, nineteen
eighty eight, I believe, Yeah, yeah, so that is just
have things changed.
Speaker 4 (46:50):
I don't think so.
Speaker 1 (46:51):
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
(47:14):
and Johnson and Johnson.
Speaker 3 (47:22):
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.
Speaker 1 (47:30):
Off.
Speaker 4 (47:31):
You've let us out. Oh goodness me.
Speaker 1 (47:41):
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.
(48:03):
This plan to market retine for off label uses was
a shredfest.
Speaker 4 (48:10):
I'm not kidding. Isn't this wild?
Speaker 3 (48:13):
They really thought that was gonna work, though, I know, I.
Speaker 4 (48:16):
Know, right every time.
Speaker 1 (48:19):
I don't know how they thought they weren't going to
get caught. It doesn't make sense.
Speaker 4 (48:23):
And they definitely got caught.
Speaker 3 (48:25):
Yeah.
Speaker 1 (48:25):
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
(48:46):
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
(49:07):
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
(49:30):
hefty fine, a total of seven and a half million dollars,
which is one of the largest ever paid for.
Speaker 4 (49:37):
An FDA violation. Wow at the time.
Speaker 1 (49:41):
Yeah, but to Ortho, to Johnson and Johnson, it may
have well have been pocket change, right, like they had actually.
Speaker 3 (49:47):
Competed to what they're about to make, Like exactly.
Speaker 1 (49:50):
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,
(50:12):
or restore a more youthful or younger dermal histologic pattern.
Speaker 4 (50:16):
End quote.
Speaker 3 (50:18):
Sorry, so it was proved to treat photoaging, but they
had to say that it doesn't treat.
Speaker 4 (50:24):
Doesn't reverse photoaging.
Speaker 5 (50:26):
Yeah, okay, yeah, histologically histologically okay, I don't know what
the standard for we'll get you know, evidence was, I guess.
Speaker 3 (50:39):
Yep.
Speaker 1 (50:40):
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.
Speaker 4 (50:59):
And you'll find it next to impossible to actually.
Speaker 1 (51:02):
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
(51:23):
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
(51:44):
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
(52:05):
the birth control pill works in part because Gregory Pinkus
measured its efficacy by testing it out on women in.
Speaker 4 (52:11):
Puerto Rico who were never told the purpose of the
pill or.
Speaker 1 (52:15):
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
(52:36):
that we have.
Speaker 3 (52:38):
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,
(53:00):
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.
Speaker 4 (53:12):
Is, and I sometimes wonder why that is.
Speaker 1 (53:15):
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
(53:35):
the worker conditions, Like do people think that it's just
going to distract from how retinoids help with acne?
Speaker 4 (53:43):
I don't know.
Speaker 3 (53:44):
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
(54:04):
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.
Speaker 1 (54:25):
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.
Speaker 3 (54:38):
No. Also, I'm not sure that we even had it
specific ethics class in med school.
Speaker 1 (54:43):
I think I did in my EPI masters.
Speaker 3 (54:47):
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.
Speaker 1 (54:59):
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
(55:20):
by an unrestricted educational grant from Orthopharmaceuticals, which is least
it's like you know, at least.
Speaker 3 (55:27):
Easily disclosed and not like in the subfooting.
Speaker 1 (55:32):
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.
Speaker 3 (55:50):
You can find the list of sources from this episode
in every single one of our episodes there.
Speaker 4 (55:53):
Check it out.
Speaker 1 (55:55):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.
Speaker 3 (56:00):
Thank you to Leona Squilacci and Tom Bryfogel for the
incredible audio mixing.
Speaker 4 (56:05):
And thank you to everyone at Exactly Right.
Speaker 3 (56:07):
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?
Speaker 1 (56:21):
And a big thank you as always to our wonderful,
generous patrons.
Speaker 4 (56:26):
We appreciate your support so so so so very much.
Speaker 3 (56:30):
Yesh, we do thank you well.
Speaker 4 (56:33):
Until next time, wash your hands you.
Speaker 3 (56:35):
Feel the animals
Speaker 5 (57:01):
E
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.
(00:23):
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
(00:46):
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
(01:06):
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.
Speaker 2 (01:17):
On the grid.
Speaker 1 (02:04):
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
(02:25):
Skin by Alan Hornblum.
Speaker 3 (02:30):
Hi, I'm Aaron Welsh and I'm Eron Auman Updike.
Speaker 1 (02:33):
And this is this podcast will kill You.
Speaker 3 (02:35):
And today's episode we are covering one half of a
big story all about retinoids.
Speaker 4 (02:45):
Yeah.
Speaker 1 (02:46):
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.
Speaker 4 (02:57):
And you know, we.
Speaker 1 (02:59):
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,
(03:23):
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.
Speaker 3 (03:40):
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.
Speaker 4 (03:49):
How recent?
Speaker 3 (03:50):
How recent?
Speaker 1 (03:51):
I mean what Tuskegee was whistleblown in the early nineteen.
Speaker 4 (03:55):
Seventies, I know, Yeah, I know, I know. And then yes,
so that is.
Speaker 1 (04:01):
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?
Speaker 3 (04:16):
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.
Speaker 4 (04:26):
And a big.
Speaker 3 (04:27):
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?
Speaker 1 (04:37):
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?
Speaker 3 (04:54):
I mean, it's a supplement's episode two point Oh oh,
can't wait for It's gonna be so fun.
Speaker 1 (04:58):
But first, but first we have quarantini dime, we sure do.
Speaker 4 (05:05):
What are we drinking this week?
Speaker 2 (05:06):
Aren arin?
Speaker 3 (05:07):
This week we could drink only skin deep skin deep ye.
Speaker 1 (05:13):
And in skin deep appropriately is carrot juice because retinoids
are derived from vitamin A ultimately, which is found in
great quantities and carrots.
Speaker 3 (05:24):
Yeah, it's beta carotene, which is like will convert into
vitamin A in your body. It's a long.
Speaker 4 (05:29):
Story technically speaking.
Speaker 1 (05:33):
And it also has ginger and lemon juice and some
simple syrup and some vodka and it's a tasty little concoction.
Speaker 4 (05:41):
I might have to play around with the ratios a
little bit, but.
Speaker 3 (05:43):
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.
Speaker 1 (05:57):
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
(06:19):
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.
Speaker 4 (06:30):
You know it's good safe, check it out.
Speaker 3 (06:33):
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.
Speaker 1 (06:53):
All right, it's a long story, so let's take a
quick break before we begin. How many of you out
(07:15):
there listening has in their bathroom cabinet a little bottle
of serum or a little tube containing retinol or retinoids.
Speaker 4 (07:25):
Too? I have two, I have one.
Speaker 3 (07:29):
Two different kinds.
Speaker 1 (07:30):
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.
Speaker 4 (07:39):
Lot of you out there.
Speaker 1 (07:41):
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
(08:01):
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
(08:22):
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
(08:44):
developed in nineteen forty seven in response to Nazi doctor
war trials.
Speaker 3 (08:48):
Ooh, Warren, that's not How have we never heard of this?
Speaker 1 (08:54):
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.
Speaker 3 (09:15):
Yeah, or maybe it was just glossed over us, like
the history prison and like yeah not not no detail
or something.
Speaker 1 (09:22):
Right, still people devaluing human life because.
Speaker 3 (09:26):
Of yeah, yeah, yeah, okay, I want to learn, right, Okay,
So what were these experiments for?
Speaker 1 (09:33):
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.
Speaker 4 (09:56):
How do highly.
Speaker 1 (09:57):
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
(10:20):
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
(10:43):
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.
(11:04):
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.
Speaker 4 (11:26):
So he tested an on humans.
Speaker 1 (11:28):
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.
Speaker 3 (11:52):
But I'm already so mad, Aaron, I don't.
Speaker 4 (11:54):
Think he's just ei. There's so many more pages being angry.
Speaker 3 (11:57):
My face is going to be like that talking about
when it wrinkles, like I'm gonna have one.
Speaker 1 (12:02):
The brow is going to be too deep for retinoids
to penetrate.
Speaker 3 (12:06):
This podcast does give me one of those constantly.
Speaker 1 (12:10):
This podcast will give you a froid brow, give you
a brow dot com worth it.
Speaker 4 (12:15):
Yep.
Speaker 1 (12:16):
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
(12:38):
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.
Speaker 3 (12:51):
Yeah.
Speaker 1 (12:52):
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
(13:13):
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
(13:37):
was limitless potential.
Speaker 4 (13:39):
Quote. All I saw.
Speaker 1 (13:41):
Before me were acres of skin. It was like a
farmer seeing a fertile field for the first time.
Speaker 4 (13:48):
End quote.
Speaker 3 (13:51):
Sorry, you go to a prison, see untold numbers of
incarcerated individual human beings, and all you see are acres
of skin.
Speaker 4 (14:04):
Acres of skin. Cool?
Speaker 3 (14:06):
H Great?
Speaker 4 (14:08):
So that stand up guy, I.
Speaker 1 (14:10):
Think gives you a little bit of a sense for
where his sense of morality was when it came to
experiments on right humans.
Speaker 3 (14:18):
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.
Speaker 1 (14:24):
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
(14:45):
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
(15:09):
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,
(15:31):
what they ate, how much they ate when they ate,
how much sun they got, when they could shower, how
often they could shower.
Speaker 4 (15:39):
All of these things.
Speaker 1 (15:40):
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
(16:02):
very cheap, and so Kligman wasted no time in setting
up shop at the prison.
Speaker 4 (16:07):
Quote.
Speaker 1 (16:07):
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
(16:29):
can believe.
Speaker 4 (16:32):
It was a wonderful time.
Speaker 3 (16:33):
It was a informed consent didn't exist. It was a
wonderful time.
Speaker 4 (16:38):
Yeah.
Speaker 3 (16:39):
Those two sentences cannot go together.
Speaker 4 (16:42):
Yeah.
Speaker 1 (16:43):
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.
Speaker 3 (16:52):
Right, It's it's obviously him looking back on his time
doing this, being like this. It was so great, wasn't it.
Speaker 4 (16:58):
Yeah? Cool?
Speaker 1 (17:01):
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.
Speaker 3 (17:14):
Well, I was just trying to remember at what point
actually IRBs became a thing clearly after this.
Speaker 1 (17:21):
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.
Speaker 4 (17:30):
Just slipped it right in there, we need more regulation.
Speaker 1 (17:33):
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
(17:55):
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
(18:16):
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.
Speaker 3 (18:36):
Yep.
Speaker 1 (18:37):
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.
Speaker 4 (18:50):
You do this all the time.
Speaker 1 (18:53):
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.
(19:17):
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
(19:37):
because of what I can do to them.
Speaker 3 (19:39):
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.
Speaker 1 (19:54):
Right, he is hailed as a modern father of dermatology.
Speaker 3 (19:57):
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.
Speaker 1 (20:05):
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.
Speaker 4 (20:21):
Right.
Speaker 1 (20:21):
This isn't a private diary, dear diary. I feel like Machiavelli.
This is like a brag.
Speaker 3 (20:28):
It's like basically the equivalent of a tweet back in
the day.
Speaker 4 (20:31):
Exactly.
Speaker 1 (20:32):
You can't take you back, No, it's it's there. And
I think what's like. Kligman is one of the individuals
(20:53):
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,
(21:13):
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
(21:35):
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
(21:57):
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
(22:18):
to cause risk to a prisoner in medical tests from
which he has no direct benefit?
Speaker 2 (22:23):
End quote?
Speaker 4 (22:24):
Seems like a rhetorical question. I don't think he answered it.
Speaker 1 (22:27):
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
(22:49):
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
(23:12):
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
(23:34):
experimentation in any capacity. I just want to put it
in historical context, like this is not a one.
Speaker 3 (23:40):
Off this which obviously just makes it that much worse.
It makes it that much for everyone and everywhere.
Speaker 1 (23:46):
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.
Speaker 4 (24:00):
I'm at Holmesburg Prison.
Speaker 1 (24:02):
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
(24:24):
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
(24:45):
just scientifically is not great.
Speaker 3 (24:48):
Not great.
Speaker 1 (24:50):
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.
Speaker 4 (25:12):
Most of these oh wow.
Speaker 1 (25:14):
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.
Speaker 4 (25:34):
How it would heal. Okay, yep.
Speaker 1 (25:37):
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
(26:00):
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.
(26:25):
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,
(26:46):
herpes virus, influenza tests that involved liver biopsies and nearly
killed seven inmates. I don't know why the liver biopsies
were needed.
Speaker 3 (26:56):
Why are you doing liver biopsies and what?
Speaker 4 (27:00):
Yep, okay, don't know.
Speaker 1 (27:03):
Radioactive isotope testing exposing people to dioxin and observing the results.
Speaker 4 (27:09):
It's like, what happens? What happens if we do this?
Speaker 1 (27:12):
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,
(27:36):
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
(27:59):
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
(28:23):
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
(28:47):
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.
Speaker 3 (29:03):
Right.
Speaker 4 (29:03):
I mean, even Kligman himself was like, right, didn't exit,
itn't exist. We didn't do that.
Speaker 1 (29:09):
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
(29:31):
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,
(29:54):
this looks like it's not where I'm going.
Speaker 4 (29:56):
We're ending the trial.
Speaker 1 (29:57):
Oh, this looks like where it's where I wanted to go.
We're ending the trial, and saying that this is exactly.
Speaker 4 (30:01):
What I wanted to find.
Speaker 1 (30:03):
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.
Speaker 4 (30:16):
By the FDA.
Speaker 1 (30:17):
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
(30:41):
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.
Speaker 3 (30:59):
Blah blah blah.
Speaker 1 (31:00):
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.
Speaker 4 (31:06):
Oh wow, yeah, that kind of thing.
Speaker 1 (31:09):
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
(31:31):
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
(31:52):
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.
Speaker 3 (32:10):
Power structure and the dynamics. Is it's very difficult to overcome,
it is, Yeah.
Speaker 1 (32:17):
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.
(32:37):
He saw the work he did as quote unquote quite
beneficial to all.
Speaker 4 (32:42):
In his mind.
Speaker 1 (32:44):
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
(33:06):
we did is offer them money for a little piece
of their skin end quote.
Speaker 3 (33:12):
All these do goods go the gooters. How dare you
be a do good doctor, ma'am?
Speaker 4 (33:19):
I know right?
Speaker 1 (33:20):
Like, where does this fit into under your hippocratic oath.
Speaker 3 (33:23):
This doctor is not supposed to be a do gooder,
who is man.
Speaker 1 (33:28):
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.
Speaker 3 (33:46):
It's like the train and the one person versus the
train and the blah blah blah.
Speaker 1 (33:51):
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
(34:14):
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.
(34:36):
Even when the lawsuits came out, which were dismissed because
of statute of limitations.
Speaker 3 (34:41):
Oh God.
Speaker 1 (34:43):
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
(35:05):
violation of the Nuremberg Code. He seemed to think that
the ends justified the means.
Speaker 4 (35:11):
Wow, but what exactly were those ends?
Speaker 1 (35:15):
Right? Was it the advancement of science, Was it relieving
people suffering? Or was it simply making.
Speaker 4 (35:22):
Money, making a buck? That's my guest, Aaron.
Speaker 1 (35:26):
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
(35:47):
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.
Speaker 3 (35:58):
For sure, because we're focusing on and like topical retinoidstadata,
vitamin as is its own thing.
Speaker 1 (36:04):
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
(36:25):
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,
(36:48):
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.
Speaker 4 (37:09):
I'm not sure.
Speaker 1 (37:10):
I don't know if it went by the name. Then
this was administered orally, and they found similar benefits.
Speaker 4 (37:17):
All of these.
Speaker 1 (37:18):
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,
(37:44):
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.
Speaker 3 (37:53):
Oh, this means it's doing things.
Speaker 4 (37:55):
This means it's doing things.
Speaker 1 (37:57):
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.
Speaker 4 (38:11):
At the prison, Kligman sought.
Speaker 1 (38:13):
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.
Speaker 4 (38:23):
At Holmsburg.
Speaker 1 (38:25):
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.
Speaker 4 (38:38):
End quote.
Speaker 3 (38:40):
Ah Okay, this kind of just keeps getting worse there,
and he keeps.
Speaker 1 (38:45):
Getting I know, you're like, surely there's not more to this.
Speaker 4 (38:48):
Oh, trust me, there is. Yeah. Yeah.
Speaker 1 (38:53):
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.
Speaker 3 (39:03):
On one percent. Yeah, oh my, yeah, that's way too strong.
Speaker 4 (39:12):
Uh.
Speaker 1 (39:12):
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
(39:34):
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,
(39:58):
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
(40:20):
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.
Speaker 4 (40:39):
Not have been better.
Speaker 1 (40:40):
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.
Speaker 4 (40:51):
The immediate success.
Speaker 1 (40:52):
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
(41:13):
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,
(41:35):
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.
Speaker 4 (41:43):
End quote.
Speaker 3 (41:46):
Aaron, these quotes that cannot be real. I know.
Speaker 1 (41:52):
I'm like, this is a caricature of what the worst like.
Did he ever study hysteria? I can only imagine, Right, I.
Speaker 3 (42:00):
Have a doctor and don't believe patients. Oh my, this
guy is so celebrated.
Speaker 1 (42:09):
I cannot I know, don't believe patients. If you believe
your patients, you're a quack, told students, like he trained students, right.
Speaker 3 (42:19):
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.
Speaker 4 (42:33):
What yeah, yep, so there you go.
Speaker 3 (42:39):
Cool, cool, cool yep.
Speaker 1 (42:41):
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
(43:02):
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
(43:26):
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,
(43:47):
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
(44:09):
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
(44:30):
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.
Speaker 4 (44:50):
Can you prescribe this for me? Okay, I'm going to
use it in.
Speaker 1 (44:52):
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.
(45:13):
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.
Speaker 3 (45:35):
I mean every single ad on a Hulu yep.
Speaker 1 (45:39):
Number two, major corporate publicity of medical researchers who abandoned
objectivity for corporate dollars on behalf of new products and
lavish pr campaigns.
Speaker 3 (45:49):
Every single dermatologist and researcher who has their own skincare
line now yep, yep.
Speaker 1 (45:55):
Number three, the extremely close relationships between pharmaceutical companies and doctors.
Speaker 3 (46:00):
Weirdly, especially true in dermatology, like very I mean there's
supposed to be more things in place for that, yeah
than there are.
Speaker 1 (46:11):
Number four the shallow perusal by the general press of
pharmaceutical company press releases in the quest for bold headlines.
Speaker 4 (46:19):
Hi.
Speaker 3 (46:20):
Yeah.
Speaker 1 (46:22):
Number five the FDA's underfunded, understaffed administrative situation in the
face of well organized corporate initiatives and sophisticated publicity techniques.
Speaker 3 (46:32):
Imagine if we funded organizations that are supposed to protect
the public.
Speaker 4 (46:37):
What a concept.
Speaker 3 (46:39):
Sorry, this was written yesterday or ID know, right, nineteen
eighty eight, I believe, Yeah, yeah, so that is just
have things changed.
Speaker 4 (46:50):
I don't think so.
Speaker 1 (46:51):
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
(47:14):
and Johnson and Johnson.
Speaker 3 (47:22):
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.
Speaker 1 (47:30):
Off.
Speaker 4 (47:31):
You've let us out. Oh goodness me.
Speaker 1 (47:41):
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.
(48:03):
This plan to market retine for off label uses was
a shredfest.
Speaker 4 (48:10):
I'm not kidding. Isn't this wild?
Speaker 3 (48:13):
They really thought that was gonna work, though, I know, I.
Speaker 4 (48:16):
Know, right every time.
Speaker 1 (48:19):
I don't know how they thought they weren't going to
get caught. It doesn't make sense.
Speaker 4 (48:23):
And they definitely got caught.
Speaker 3 (48:25):
Yeah.
Speaker 1 (48:25):
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
(48:46):
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
(49:07):
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
(49:30):
hefty fine, a total of seven and a half million dollars,
which is one of the largest ever paid for.
Speaker 4 (49:37):
An FDA violation. Wow at the time.
Speaker 1 (49:41):
Yeah, but to Ortho, to Johnson and Johnson, it may
have well have been pocket change, right, like they had actually.
Speaker 3 (49:47):
Competed to what they're about to make, Like exactly.
Speaker 1 (49:50):
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,
(50:12):
or restore a more youthful or younger dermal histologic pattern.
Speaker 4 (50:16):
End quote.
Speaker 3 (50:18):
Sorry, so it was proved to treat photoaging, but they
had to say that it doesn't treat.
Speaker 4 (50:24):
Doesn't reverse photoaging.
Speaker 5 (50:26):
Yeah, okay, yeah, histologically histologically okay, I don't know what
the standard for we'll get you know, evidence was, I guess.
Speaker 3 (50:39):
Yep.
Speaker 1 (50:40):
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.
Speaker 4 (50:59):
And you'll find it next to impossible to actually.
Speaker 1 (51:02):
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
(51:23):
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
(51:44):
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
(52:05):
the birth control pill works in part because Gregory Pinkus
measured its efficacy by testing it out on women in.
Speaker 4 (52:11):
Puerto Rico who were never told the purpose of the
pill or.
Speaker 1 (52:15):
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
(52:36):
that we have.
Speaker 3 (52:38):
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,
(53:00):
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.
Speaker 4 (53:12):
Is, and I sometimes wonder why that is.
Speaker 1 (53:15):
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
(53:35):
the worker conditions, Like do people think that it's just
going to distract from how retinoids help with acne?
Speaker 4 (53:43):
I don't know.
Speaker 3 (53:44):
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
(54:04):
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.
Speaker 1 (54:25):
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.
Speaker 3 (54:38):
No. Also, I'm not sure that we even had it
specific ethics class in med school.
Speaker 1 (54:43):
I think I did in my EPI masters.
Speaker 3 (54:47):
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.
Speaker 1 (54:59):
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
(55:20):
by an unrestricted educational grant from Orthopharmaceuticals, which is least
it's like you know, at least.
Speaker 3 (55:27):
Easily disclosed and not like in the subfooting.
Speaker 1 (55:32):
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.
Speaker 3 (55:50):
You can find the list of sources from this episode
in every single one of our episodes there.
Speaker 4 (55:53):
Check it out.
Speaker 1 (55:55):
Thank you to Bloodmobile for providing the music for this
episode and all of our episodes.
Speaker 3 (56:00):
Thank you to Leona Squilacci and Tom Bryfogel for the
incredible audio mixing.
Speaker 4 (56:05):
And thank you to everyone at Exactly Right.
Speaker 3 (56:07):
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?
Speaker 1 (56:21):
And a big thank you as always to our wonderful,
generous patrons.
Speaker 4 (56:26):
We appreciate your support so so so so very much.
Speaker 3 (56:30):
Yesh, we do thank you well.
Speaker 4 (56:33):
Until next time, wash your hands you.
Speaker 3 (56:35):
Feel the animals
Speaker 5 (57:01):
E
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Erin Welsh
Erin Allmann Updyke
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