This Podcast Will Kill YouOf the many topics our podcast has covered in the past, from smallpox to scurvy, vaccines to birth control and beyond, one factor has linked nearly all of them: HeLa cells. These cells and the woman from whom they were taken have often remained behind the scenes in the coverage of these topics, but they have nevertheless been absolutely fundamental in the development of technologies, the advancement of knowledge, and the discussions of ethics, ownership, and informed consent. In this week’s episode, we want to do more than acknowledge the contribution of Henrietta Lacks and her cells to the field of biomedical science. We want to explore what it is about HeLa cells and other cell lines that makes them ‘immortal’. We want to learn what Henrietta was like as a person. We want to ask how it was possible for her cells to be taken from her without her consent or knowledge. And we want to share the tremendous impact Henrietta and her cells have made and continue to make on our world in so many ways.
For more information about the Henrietta Lacks Foundation, check out the website.
Hi, I'm Erin Welsh and I'm Aaron Allman Updike and.
This is this podcast will kill you.
Yeah, welcome everyone.
Welcome, Welcome this episode. I'm very excited about it because it's fair very different than our normal episodes.
It's a very different I have can I be completely honest. I was really stressed out about it, say it has been so different than our normal episodes. But finally today as I was like organizing all my notes, I got really excited about it.
Oh good, okay, good. I'm very excited to hear what you're gonna tell me.
Yeah. I hope that you like it.
I'm sure that I will, Erin, Come on, I'm very excited to learn all about what you're gonna tell me today, Erin, because I know very little about it. Well, and your nerves may have gone away, but mine are still here and I'm still nervous that I'm not going to do a good job. But you know what, just uh, it'll be okay.
It's okay that we always feel that way and we just do our best.
Erin, that's true, that's true, we do do our best.
Yeah, what are we even talking about today?
Aarin?
I feel like the suspense has been building.
I know, I know. We are talking today about Henrietta Lax, Henrietta Lax and her cells and her cells.
You may have heard her name in your intro bio class, or in your cell bioclass, or maybe in your class on medical ethics.
Maybe in the HBO movie that just came out. There are tons of different ways that you may have heard about Henrietta Lax, and we are going to kind of like try to cover a lot of those different ways or context in which you may have heard her name, including things like tissue culture and the ethics of informed consent, and also like who was Henrietta Lax?
Yeah, that's the part I'm most excited about.
Yeah, me too. And there's a lot to cover. So maybe we should begin where we usually do.
We should, which is always with a quarantiny.
A quarantiny, Aaron, what are we drinking this week?
This week we're drinking ambrosia. Ambrosia, drink of the gods that confers immortality.
Immortality, and we will learn so much more about what immortal means. Oh, I'm really.
Excited to talk about it.
Yeah, okay, good, okay, But first, what is in ambrosia?
Well, of course, being in the Midwest, ambrosia salad's like a Midwest thing, right.
I think so? Or is it a Southern thing.
Maybe it's a Southern thing. I feel like I've seen it here. Anyways, it's rum and coconut cream, pineapple juice, orange juice, some grenadine. You blend it all up. So it's like an ambrosia salad in a glass with rum.
Yeah, it's I think it's going to be better than like the actual ambrosia fruit salad.
I hope. So because I'm not a big fan.
You mean you don't like mayonnaise with your fruit? Wait?
Is it mayonnaise? I thought it was cool whip. Oh no, it is.
Well it's not cool whip. It's actually sour cream. I oh okay, just like yeah, but I think you could also include mayonnaise or cottage cheese or yogurt or cream cheese or putting them on the Wikipedia page.
I was like, are you looking at it? You're looking at a rescue right now. Oh well, anyways, we'll post the full recipe for that quarantine as well as our non alcoholic plusy berita on our website. This podcast will Kill You dot com and all of our social media channels.
Yes, indeed, all right, what other business do we have to take care of? Well?
As always, we have a good Reads list and a bookshop dot org link on our website. We also have merch by incredible artists on our website. We have links to transcripts. We have non alcoholic episodes. So much this podcast will kill you dot com.
Oh, Aaron, good job everything. I was like, is there anything? I can't think of anything else?
I think that's everything?
All right? Well, okay in that case, shall we take a break and then get started. Let's do it.
So, let's start with what a cell culture is, because a lot of people that aren't you, Aaron maybe have never used cell culture. So cell culture essentially just means growing cells. Any kind of cells could be human, could be other animals, could be bacteria, yeast, whatever, in some kind of artificial medium, like in a bottle or a petri dish something like that. So we have cell cultures of all different kinds of cells. In order to grow cells of pretty much any tissue type, you just need some basic environmental conditions, like a stable temperature, a nice pH some kind of substrate which might just be like a petri dish, and then you need growth media, which is just a fancy word for fluid or gel or something that has nutrients vitamins, salt, sugars so that cells can grow and thrive and reproduce. So the use of cell culture in biology at this point is so essential to the study of both basic science, like our basic understanding of cell biology, and also to applied clinical research. We use cell cultures to understand underlying cellular mechanisms that underlie all of life on planet Earth, but we also use them to study like new drugs to see if they're toxic to cells, to understand the effects of radiation or viruses or cancer on cell function. We use cell culture to grow viruses to make vaccines like the rabies vaccine or hepatitis or chicken pox vaccines. And we also use cell cultures for a ton of what are called biopharmaceuticals, which are things that cells produce that we can then use as drugs, like enzymes, proteins, antibodies that we use for cancer treatment or infectious disease treatment. We produce hormones, clotting factors, like so many things that people rely on every day are only possible because of cell culture.
It's unbelievable.
It's really it's amazing.
It's like hard to overstate how basic they are, in like essential.
Essential, absolutely.
I used HeLa and mouse macrophage cells as an undergrad to study like these different proteins on plague bacteria to see which ones were involved in adhesion or invasion of the cells.
That sounds incredible. My labs in my master's program, we used verro cells, which are from an African green monkey kidney, to test whether the viruses that we were finding in waste in seawater were infectious. Although I didn't do that because I could never keep my cells alive.
I just remember being so fascinated by when I was doing these essays by making sure that like, oh, are the bacteria actually infecting these cells, and you would like put the flask under the scope and see everything. It was I couldn't believe what I was seeing that like this incredible process that you read about. It was just I still can't get over it.
I can tell that you're getting little.
Chills when I'm getting little chills.
Okay, So Aarin in our kind of history section, you'll be going through the history of how HeLa cells which are the cells that were taken from Henrietta Lax without her permission and used and how big of an impact they've had on scientific knowledge. But the question that I want to answer in this section is why were Henrietta LAX's cells such a massive step forward in cell culture technology and what makes the cell lines that we use for cell culture today so different than what was used before HeLa.
Mm hmm, okay, I'm very excited.
Oh my Tish, it's like, it's pretty cool. So before Henrietta Lxis cells were taken from her and became what we now know of as HeLa cells, scientists were still trying to grow mammalian and human cells from tissues, but they always died, and usually after a pretty short period of time, so you could run like one experiment and and then you'd have to harvest more tissue or more cells and start all over. So the reason that HeLa changed everything is because Henrietta Laxis cells didn't die. They kept growing and replicating and continue to do so today like seventy years later. And so Henrietta Laxis cells became what is known as a cell line, and a cell line essentially means cells from whatever humans or other animals, insects, plants, bacteria, from any tissue that can be grown in culture indefinitely. Why and how?
Yeah?
Okay, so let's first understand Henrietta laxis cells, the first cell line. These cells came from a sample of tissue from cervical cancer. And we already discussed in our HPV episode how cervical cancer develops as a result of HPV infection, so I'll just ever so briefly review that for anyone who didn't listen or forgot. We know that high risk HPV strains have a couple of different proteins E six and E seven that integrate into our genome, like get into our DNA and turn off a few genes called tumor suppressor genes. And what this does is that allows for cells to grow in an uncontrolled manner. So all cells follow a very specific cell cycle as they grow and divide, and they spend most of their time in a phase called interphase where they grow and also replicate their DNA, and then they undergo mitosis, which is the actual division of chromosomes, and then cytokinesis, which is when the cell divides into two separate cells and along the way. There's a lot of different checkpoints usually during that interphase that ensure that cells grow at an appropriate rate so not too quickly. We have to make sure there's enough nutrients to sustain growth and division, and to make sure that the cells aren't replicating any mistakes or problems in the DNA. So the proteins that we talked about in the HPV episode affect these parts of the cell cycle. Primarily, they encourage excessive growth and division. That allows for division of cells even if there are problems or mistakes in the DNA, or even if there's maybe not enough nutrients, they'll just keep growing and growing. So that's part of the equation. But that isn't quite enough to cause cells to grow indefinitely. Yeah, that's part of what accounts for cells that can grow more rapidly and persist longer. But there's another piece that we have to understand, and that is telomere's.
Oh I love them, I know, right.
So a telomere is the end part of our chromosomes. It's like a cap on the end of our chromosomes. Very very tips. In general, during normal DNA replication, it can be very difficult for our cells to fully replicate the entirety of the chromosome. So often the very very ends of the chromosomes, where the telomeres are actually becomes shorter with each cell division. This is normal, This happens as a normal part of cell division. So the telomeres are there as like an insurance policy, like Okay, well we miss the very end, but we didn't really need it. No big deal. But as cells divide and divide, those ends get shorter and shorter with each division, and eventually, once the telomeres are sufficiently shortened, it actually triggers an arrest of growth and a rest of the cell cycle and no more cell division. So you can kind of think of it like every cell having a limited number of times it can divide before those telomeres get too short, like you've heard like your heart only has a certain number of beats or whatever. Yeah, I don't think that's really true, but it's kind of like that idea, all right, But in some cells, like cancer cells, they've lost the ability to sense when telomeres get too short, and they keep on dividing and dividing and dividing, so they get shorter and shorter with each division. Now eventually those cells too will die or at least stop replicating because of damage. Once you get too damage in your DNA, then you just have damaged DNA and that cell can't continue to divide. So there has to be something else going on here. Yeah, how can this cell line keep dividing indefinitely and truly indefinitely?
Does it add on length erin?
It?
Sure does. Interest turns out there's an entire enzyme group of enzymes called tilomera. I don't know if that's the proper way to pronounce it, but I think it's close. Tilomerase is an enzyme that specifically replicates just those telomere sequences to make sure that they are not lost or shortened during replication, which allows cells to escape this normal What is a normal mechanism that says cells should only divide a certain number of times and then stop dividing. If you turn telomerase on and you have that enzyme present, then these cells will be able to divide forever. And as it turns out, over ninety percent of cancer cells, most cancer cells have additional mutations beyond just in those tumor suppressor genes that we talked about that turn on the expression of tilomerase.
And so tilamera and telomeres also have something to do with aging, like the process of aging, because I know, yeah, that's what a lot of like anti aging studies or whatever, yes, focus on.
It's thought that they have a large amount to do with aging. That like cellular senescence is governed by telomeres and like the length of telomeres.
Right, and so it would make sense that like more quote unquote insults to your body through stress or inflammation or whatever would lead to more like cells turning over more quick rap which leads to faster aging exactly.
Yeah, at a cellular level, like aging at a cellular level.
But there's also the downside that it is cancer.
It is cancer. Interesting, yes, And so that's because Okay, I feel like what you're getting at is some really interesting things, right, Because the thing about HeLa and many of our cell lines is that they have mutations in not just tilomerase, right, they have mutations in these other properties like P fifty three, like p retinoblastoma, these other genes that also control like how rapid the cell grows and if it can grow, but still miss other important cell cycle checkpoints like that DNA is intact et cetera. Tilomerase is separate from all of that m HM. So if you could induce just tulomerase, you could, in theory get a cell to divide indefinitely that doesn't have the other properties of cancers.
Right, Like, there would still be all of the checks in place, except for the fact that the telomeres would just not.
Not shorten exactly right. And so that is actually a way that people have started to generate cell lines today.
Interesting, right, it's are these cell lines prietary?
Oh? Probably? Yeah, yeah, I mean every cell line that's developed it yeawadays yeah, yeah, but yeah, So today we have a lot of different cell lines. HeLa was the first, but now we have so so so many. We have cell lines from mice, from dogs, from humans, from so many different animals. We have them from kidney cells, from ovaries, from embryos, We have cell lines from so many different things that we can use for very specific purposes. And because we've learned so much about the cell cycle and about these specific controls on what can make a cell immortal, we can then create new cell lines. We can use viral vectors or engineer virul like HPV to integrate into genomes and cause these changes that can then turn a normal cell into an immortal cell. Or like I mentioned already, we can just induce the production of tulomerace so that we can then hopefully keep all of the other normal cellular architecture rather than more cancerous architecture that HPV infection would cause.
Interesting, I know, Oh this is kind of tangentially related.
Okay, but we got a couple.
Of emails from people reminding us that cervical cancer is not one, absolutely, one hundred percent associated with HPV. Yes, it's very, very very like the vast vast majority, like ninety nine percent, but there are some cases that are not caused by HPV.
Yeah, we should have said that in our intro as a correction. But yes, it's like ninety nine point seven or ninety nine point nine percent of all cervical cancers are known to be associated and caused by HPV. Yes. Yeah, So thank you to the people who reached out.
Yes, thank you.
Anyways, so back to cell lines. The last thing that I want to point out that I think is important not only to kind of understand cell culture and cell lines, but also because when we kind of talk about the current status of cell culture. I want to talk a little bit more about it is the difference between an immortal cell line and a stem cell HM. So I think a lot of times when people hear, especially if you don't have a lot of training in biology and like don't work with cell cultures all the time, when you hear cell culture, a lot of times what people think of are stem cells. And I think that's because they get a lot of headlines right because they can be controversial. So immortal cell lines like HeLa and stem cells are not the same. Both are used in scientific research, and both are incredibly important, but there's some pretty important differences. Immortalized cell lines like HeLa come from what are called primary tissues to begin with, which which means they come from differentiated like you can think of them as grown up cells like kidney cells or macrophages, which are white blood cells, or cervical epithelial cancer cells in the case of HeLa. So these cells are differentiated, They have a particular function in our bodies, They have a specific kind of architecture, and so cells from a kidney are going to be different than cells from a cervix. And whenever these cells divide, even when they do so indefinitely, they stay roughly the same. Stem cells, on the other hand, are undifferentiated, so these cells have the potential to become any or many different cell types, from like a neuron to a kidney, to a liver cell, to a muscle cell to whatever. Right, So sometimes people describe stem cells as like a little kid that has the potential to be anything they want to be when they grow up, and differentiated cells as a grown up who has one job or function. Oh wow, right, I don't be said. I don't like that analogy at all, because yeah, it can change careers. But anyways, I really tried to come up with a better one, and I couldn't, so that's that's what I got. But anyways, so that's kind of the biggest difference between stem cells and differentiated kind of adult cells. There are two different kinds of stem cells as well. In humans. There's embryonic stem cells, which are like where we began, so a zygote, because embryonic stem cells that's how we all formed in utero, and these cells can become literally any cell type. They become every single cell in our body. But even as grown humans, we have stem cells in our bodies as well. They're called somatic stem cells, meaning they are in our body currently rather than in an embryo. And these are very important because they serve to regenerate cells in our body that need regeneration. So like in our skin, for example, in the basal layer, the very bottom layer, there are stem cells that are epidermal stem cells that not only continually divide and produce more epidermal stem cells, but they can also differentiate into grown up skin cells. Right. And then we also have like in our bone marrow, hematopoetic stem cells, which can become all of our blood cells, red blood cells, white blood cells, platelets. Right. So the big difference between embryonic stem cells and most somatic stem cells is that these somatic stem cells can only become like one or a few different kinds of cells, whereas embryonic can become.
Like literally really anything, right, right.
So that's just like to keep in mind they're different. Most cell lines that we use don't come from embryos or embryonic stem cells. They come from differentiated animal or human cells. So they come from a piece of tissue and then they are made into a cell line.
M H.
That's it.
Aaron do you have any other questions for me about cell culture?
Oh, I'm trying to think so the whole thing about there's a limited number of times that a particular cell line can or a particular cell can replicate before the machinery just shuts down. That's that's the Hayflick limit. Right, Yeah?
Does that?
How much does that vary across different cell types?
Oh, that's a good question. I don't fully know, but based on how different cell types function in adult humans, I would guess that there's quite a bit of variability, and maybe not necessarily in what that limit could theoretically be, but at least in what that limit is in a normal like human body for example, right, like practice exactly.
Okay, Yeah, interesting.
So Aaron, Yes, let's talk about where these cells came from.
Let's do it. Let's take a quick break first. So, Aaron, you have taken us through HeLa cells, what they are, some of what they can be used to do, and lots of other aspects of tissue culture. But as we know, that's just one part of the story of HeLa, right, and I feel super lucky that I get to tell the rest of that story, or at least like a good chunk of it, which is the story of the woman behind Thosesells, Henrietta Lacks, and the legacy she has left behind, both in terms of scientific achievements, but also in raising these important questions of ownership, informed consent, what it means to be immortal. Right off the bat, I want to say that this is such a big story that I can't focus on all of it. But fortunately there are other great resources out there, including the book where I got most of this information, The Immortal Life of Henrietta Lax by Rebecca Sclute, And there's also a movie based on the book on HBO. And will of course post these resources on our website so you can read more. Okay, So, who was Henriette A.
Lax? Right?
The answer you would probably come across in most biology textbooks, especially ones that were published like let's say fifteen years ago or so, is that, in short, Henrietta was a black woman who died of cervical cancer in nineteen fifty one at the age of thirty one, and from whom cells were taken. A lot of books might actually say donated. That gave rise to the most ubiquitous immortal cell culture line that has been used in every type of scientific research you could think of, literally literally, and that alone is an incredibly impressive one sentence, maybe like a run on sentence a biography, But what it doesn't tell you is that she was also a mother, She was a daughter, a wife, a friend, a sister, someone who is more than just those cells and the legacy that they have left and continue to leave behind. One of the themes that has come up more than once on this podcast, many times on this podcast is the problem with the lack of humanity in medicine or science. It's often more straightforward or efficient to look for what we can measure or observe directly to make a diagnosis or to detect patterns within a population. And of course the application of the statistical analysis and data collection and the development of diagnostic criteria, it's all been hugely beneficial. But you know how people say, you can't see the forest for the trees. Yeah, this is kind of like the opposite losing sight of the trees for the forest. It's so important to remember, but way too easy to forget that behind each of those data points, behind each person diagnosed with a disease, behind each person who makes a discovery or a diagnosis is a human being with an entire history and life of their own. And I think keeping that humanity in science and seeing both the forest and the trees probably makes you a better scientist and a better physician and probably just a better human overall. And that's a big reason kind of why we include these first hand accounts in our episodes, to ground these topics in real life, to remind ourselves and hopefully listeners that, like, these diseases don't happen just like in a textbook, like they happen to real people. People experience them. And that's also why for this episode, rather than including a first hand account, we wanted to focus just this almost this whole history section on this person, on the first hand account on the person behind these HeLa cells.
Yeah, that's we weren't lying when we said this is a very different episode.
Yeah, So who was HeLa? We keep saying HeLa, HeLa H E like capital H, lowercase E, capital L lowercase A. HeLa stands for Henrietta Lax, the first two letters of her first and last name. Henrietta Lax was born Loretta Pleasant in Roanoke, Virginia, on August first, nineteen twenty. Henriette was only four when her mother, Eliza died, and to help take care of Henrietta and her nine siblings, her father Johnny brought the family to Clover, Virginia, where Henrietta lived with her grandfather, Tommy Lax. Johnny's family had lived in Clover for decades. His ancestors had farmed the land while enslaved, and they continued to farm tobacco after slavery ended. Henrietta spent her childhood working on the farm, milking cows, feeding chickens, taking care of the pigs and horses, planting and collecting tobacco leaves. Getting to school wasn't as simple as hopping on a bus. It was a long two mile walk each way, and Henrietta made that walk every day through sixth grade. In her free time, she and her cousins would swim in the swimming hole, or play tag or hopscotch. Or they would take their earnings and go to the movie theater, where they would watch black and white movies, sitting the only place they were allowed, which was in the colored section. Henrietta's friends described her as lively and tough, someone who always stood her ground, but also someone who was warm and sweet and generous, the person who made you see life in technicolor when you were around her. When she was twenty, Henrietta married David or Day Lax. Over the course of their relationship, they would have five children, Lawrence, Elsie, David or Sonny, Deborah, and Zakaria born Joseph. Not long after getting married, Henrietta and Day moved up to Baltimore, where there was a huge boom in industrial jobs now that the US had entered into World War Two. Henrietta didn't love living in Baltimore in the city, so she would take the kids back to Clover as often as she could, which was most every weekend, and among her friends and family, Henrietta was known for being an amazing cook, spending hours every day putting together rice pudding or slow cooked greens, or spaghetti and meatballs, cooking tons and tons of foods so she could feed her kids and her husband, as well as whatever cousins happened to stop by. In the evenings, she and Day would play cards and listen to music if he was off work, and if he wasn't, she would often go out dancing with her friend Sadie. But life for Henrietta wasn't always this house full of delicious food or nights out dancing. There were also some incredibly tough times, like when she took her daughter Elsie to Crownsville State Hospital, which used to be known as the Hospital for the negro Insane. Elsie, who was deaf and seemed to suffer from epilepsy, would die in that hospital when she was fifteen, which was after Henrietta died, but Henrietta's family talked about how dropping Elsie off there was one of the most difficult times for Henrietta, something that she never quite recovered from, and so for ten years Henrietta and her family lived in Baltimore through these ups and downs, and then one cold and rainy January day in nineteen fifty one day drove Henrietta to Johns Hopkins Hospital, where she had an appointment to check out what she called a knot on her womb. Just a few months before this appointment, she had been at the same hospital where she had given birth to Zacharia, but there was no note left behind about this knot or lump, or any sort of cervical lesion or regular larity. But she knew that there was something there, something that was causing her a lot of pain and irregular bleeding. She saw a local doctor first, who said it was a syphilis sore, but the test came back negative, and so he recommended that she had all the way to Johns Hopkins, which is a twenty mile drive, And there wasn't anything particularly special about Johns Hopkins itself. It was just that the other major hospitals that were closer wouldn't treat black people, even Johns Hopkins was segregated. At Hopkins, she was seen by gynecologist Howard Jones, who took note of the pain that she described, the bleeding in between periods, and the fact that she felt a lump on the neck of her womb. And when he examined her, he found the lump that she mentioned, which he described as a cervical tumor, one unlike any he had ever seen before and he would never see the likes of again. It was a hard mass about the side a nickel, but unlike other cervical lesions, this was shiny and purple. He compared it to grape jello. And it bled so easily, like just with the smallest sort of like poking. Yeah, he cut off a little bit for a biopsy and told Henrietta to go home and wait for an answer, and she didn't have to wait long. A few days later, on February fifth, nineteen fifty one, Henrietta received the news that the tumor on her cervix was malignant and that she would have to return to the hospital for treatment, which at the time consisted of radium tubes being stitched into the tumor and nearby tissue, which sounds incredibly painful. So the next day she was back in the hospital undergoing this painful procedure. Fortunately, while unconscious under anesthesia and during this procedure, the surgeon, Lawrence Wharton Junior, sliced two dime sized pieces of tissue from rietta cervix, one from the region where there was a tumor and the other from the unaffected region. Dime size seems big.
But it does seem big, yeah.
He then packaged these up to be sent to a tissue culture lab run by a guy named George Guy, where they were then processed by a lab employee named Mary kubachk. Mary cut up the tissue into tiny, tiny bits and placed them into culture tubes with nutritional broth, making sure to keep the tumor tissue separate from the normal tissue. She labeled the tub's hila the first two letters, like I said, of Henrietta Lack's first and last name, and that was the standard naming procedure in the lab. Mary didn't expect much to happen, honestly, because the lab had worked on cell culture for years and the highly sought after immortal human cell line was beginning to feel like a pipe dream.
It's so, can I ask a question? Yeah? So was this a lab that like they were just taking samples from everyone, just trying to grow cells unsuccessfully?
Yeah?
Okay, okay, yeah, I mean, and tissue culture had kind of like fallen out of fashion for a while, and so this like this lab was kind.
Of one of the main ones still working on it, still trying, Yeah, because it seemed hopeless to find, you know, this like immortal cell line where you could actually do sustained research on a particular cell.
Yeah. And was it kind of standard practice that surgeons would take samples of everyone that they were operating. Yes, absolutely.
So that's that's what's sort of the interesting thing, and it's also what surprised me, and I to be honest of that. In the Immortal Life book, which was published in twenty ten, I believe, I'm not sure whether anything has changed, but at least according to that book, like a lot of the you know, ownership of tissue and in the operating room, like once that tissue is removed from your body, whether it's your appendix, whether it's whatever, that no longer belongs to you, and you as an individual can't. Like there's been a lot of legal battles over the ownership of cell lines, and what seems to be the case is that an individual cannot own their own cell lines, which I think is very interesting unless you were, like were scientists, and you've developed it yourself.
You develop your own cell line, then you can, but if someone takes it from you.
Right anyway?
Yeah?
Sorry, so yeah and so yeah, George and his wife Margaret had worked for years and years for an immortal cell line. Wait they were married, yes? Oh so so Margaret different than Mary? Oh yeah, but Margaret also worked in the lab. Yeah, okay, okay, And apparently an immortal cell line had been found before using my cells. But the guys didn't want my cells. They wanted to achieve this with human cells, and so they tried and failed, and they tried and failed for thirty years.
Wow.
So you asked, where did they get all of this to shoot to try on?
Yeah?
Yeah, I mean quote unquote donation, right, Like, so they would partner with different physicians or surgeons who would take it from a patient, and way more often than not. I mean it was like the standard rule was to do this without the patient's knowledge, without their consent, and that was the common practice at the time. I think that there are some different consent rules today in terms of like, but I don't think it's I don't think you are legally requite you got it.
I'll talk a little bit more about it.
Okay, good, Okay, it's surprisingly correct me if I'm wrong. Not that different.
Today, it's not Aaron.
Yeah.
Yeah. So anyway, one of the doctors that George guy had partnered with was this guy named Richard Ti Lind who was a gynecologist trying to get to the bottom of whether or not in C two cervical cancer posed a threat and could become invasive or whether it would just remain in place. So we talked a little bit about this discussion in our HPV episode. Right yeah, and Ti Lind was firmly in the inc two cancers are pre cancers and super dangerous camp. So he was like, Okay, if only I can compare the cell types of these two cancers alongside normal cervical cells, I can show that I've been right all along and that all of these hysterectomies I've performed were not unwarranted. So he was like a big you know, Oh there's cancer. We're going to do a history and to cut the whole thing out. Yeah, yeah, exactly. And so he formed a deal with George Guy where he would provide Guy with cervical cancer tissue from his patients, and Guy would try to culture the cells.
Okay, it's all coming together.
Here we go. Any person who walked into Johns Hopkins and was diagnosed with cervical cancer would have a tiny bit of their tissue sent off to George Guy's lab without their knowledge, needless to sa ignore their consent. Okay, one of these people was Henrietta Lax. So back to Henrietta cells in a lab. Usually, what happened next, and what Mary certainly expected to happen, was that the cells in these tubes would maybe hang on for a few days at most, but would eventually die. Yeah, and this is exactly what did happen to the bits of tissue taken from the unaffected region of Henrietta cervix. But it didn't happen, not even close to the bits of cancerous tissue. The cells in those tubes didn't just hang in there. They grew and they grew and they grew. Mary had never seen anything like it before, and she hurried off to tell George. After hearing the news from Mary, it occurred to him that this could be what they've been looking for all of those decades, finally an immortal cell line, and he wasn't shy about his discovery. He made an announcement on television, holding up a tube of cells that he promised would help conquer cancer. He told his colleagues, who asked him to send them some of the cells, that they could play around with them, and then when they received the cells, they in turn grew more and sent those around the world. But as the news of this immortal human cell line called Hilo was spreading among the medical community, not just at Johns Hopkins, but seriously around the world, there was one person who knew nothing about it, the person whose name was on those cells, the person from whom they had been taken, Henrietta Lacks. By the time Guy had made his television appearance, Henrietta had returned home from the hospital, and although initially she seemed to be getting better from the radium treatments, the improvements didn't last. Over the next several months, Henrietta grew weaker and felt aches and pains in her abdomen. She hid it well, though, with just her husband and a few of her friends and cousins in the know, but then she took a turn for the worse. Follow Up doctor's visits had found a mass attached to repelvic wall and tumors on her uterus, kidneys, and urethra. Her pain was unbearable to the point where she just couldn't hide it anymore, and her doctors wrote that treatment was not really possible. The tumors were inoperable and pain relief was the only option, which was for the most part, seemed to be ineffective. During one of these doctor's visits, actually to Lynd tried to take more of the tissue from Henrietta cervix again without her consent or knowledge, but it was too full of toxins due to her advanced disease, and the cells died in culture. Henrietta spent the last month of her life in the hospital at Johns Hopkins, dealing with unbearable pain, high fevers, nausea, and new tumors that seemed to appear daily. When Day brought the children to visit, she watched them through the window until she was unable to get out of bed anymore. And on October fourth, nineteen fifty one, Henrietta Lax died, and while her family and friends saw it as an occasion for mourning, George Guy saw it as an opportunity to collect more samples from this woman who produced the first immortal cell culture line what it was. Yeah, So he asked Day for permission for an autopsy without making it explicit that they wanted more samples from her, or that they got samples from her in the first place.
The first place.
Yeah, And I think what's interesting about this is that while it was legal at this time to take tissue from a living person without their consent, it was not legal to perform an autopsy or take tissue from the deceased without consent.
Right, and that's still true. Like the rules that govern what you can do with tissues from a dead body are very.
Strict, right they are, but they're not as strict for those that are living, which is just fascinating.
It's so bizarre.
Yeah, and at first day said no way, but they asked again when he came to the hospital, and he finally agreed to a partial autopsy. Mary Kubachak, who first cultured Henrietta cells, stood next to the pathologist as he cut samples from Henriette's bladder, bowel, uterus, kidney, vagina, ovary, appendix, liver, heart, lungs, and of course cervix, placing them into Petrie dishes for later research. Finally, the autopsy was complete and Henrietta was allowed to rest. She was buried in the cemetery behind the house where she grew up in Clover. But as we know, just because Henrietta stopped living doesn't mean she stopped impacting people's lives. There's this quote by someone named Irvin Yallom, where the basic gist of it is that everybody dies twice, the first being like your actual death, and the second when the last person who knows you dies. Yeah, and if that's the case, Henrietta's memory will be carried on for a very long time, in part due to the important conversations that have taken place because of her quote unquote donation and this question of consent, and in part because of the many people who have done so much to bring awareness to her life and experiences, and another part, again due to the incredible achievements made possible by HeLa cells. So let's talk a little bit about those.
Yes, let's so.
As I mentioned, even before Henrietta died, her cells were being sent all over the world to laboratories, not just in biomedical science, but chemistry, physics, engineering, I mean, you name it, like you said, any kind of research you could imagine, for sure HeLa cells.
Have been involved. Yeah, definitely.
And even though the cells were pretty easy to maintain in the lab, demand still outpaced supply, like by a lot. In nineteen fifty two, the United States experienced the worst polio outbreak in the nation's history, with thousands killed and tens of thousands left paralyzed, and everyone demanding a vaccine for the disease. And even though there were many people researching a polio vaccine, as we know from our polio episode Back all the Way in Season one, A Long time Ago, Long time Ago. Progress was slow because the viral rus was difficult to grow in cell culture and often had to be grown in live monkeys. That is until HeLa cells came along wow which were found to be able to be infected with poliovirus. A massive cell production laboratory was set up at Tuskegee University, the first of its kind. At first, the cells that were produced here were pretty much only for polio research, but eventually, when it became apparent that there was not going to be a shortage of HeLa cells, the Tuskegee Center began sending the cells not just to polio labs, but to anyone who wanted to use the cells to study basically anything. Ten dollars a sample plus air express fees. These cells were soon used to study all kinds of viruses, to develop and standardized tissue culture techniques, to work on best practices for freezing and storing cells, and so much more. Aaron, you went into a bunch of the things. And it's funny. When I was planning on this episode, I was like, oh, I'm going to go through all the things that they accomplished, like, there's no way to even begin to list them.
It's yeah.
And this early work though, using helo cells helped to build the foundation of a field that would later go on to allow for stem cell isolation, cloning of whole animals in vitro fertilization. The study of helo cells also led to the discovery that there weren't forty eight, but rather forty six human chromosomes, and then this then led to the growth of the field of diagnosis of genetic diseases involving chromosome abnormalities such as Down syndrome or Kleinfelter syndrome or Turner syndrome. Wow. Yeah. Helo cells were blasted with radiation during the Cold War to look at the effects of radiation on a cellular level, or they were used to observe the effects of steroids, hormones, vitamins, cancer, stressors, bacteria. Basically, if you can think of a biomedical or really any kind of research topic, helo cells were there as part of it. It was clear that the application of HeLa cells in biomedical research was basically endless, and soon the demand for the cells once again outpaced the production capacity of Tuskegee. So a new company was started, Microbiological Associates, which shipped out Henrietta's cells to whoever could pay. And even though you probably would have guessed this already, all note that no one in the Lax family had been told about this endeavor, much less given any compensation for the industry that had grown out of the cells taken from Henrietta without her consent. At this point, the excitement around Henrietta's cells had grown beyond just what people were using them to do research on the public had started to learn about them as well. News articles began appearing about the cells, but these articles didn't focus just on the scientific achievements made possible by HeLa cells. They also wanted to talk about the woman herself. But this presented an issue for the doctors who took and used her cells without her permission, using her real name, and the article would not only link the Lax family to those cells, meaning whatever genetic or cellular information that arose from this research could be tied to them. But another reason, and maybe the real reason that Tilland and Guy cared was because it meant that the Lax family would also then learn that Henrietta cells were taken without her permission to create a profitable industry. The laws at the time weren't as protective of a patient's rights as they were today, even though it's only marginally more in terms of informed consent and patient confidentiality, but it was still clear at that point that that's where the laws were headed, and as a compromise, the editors of some of these articles agreed to change her name Henrietta's name to Helen Ell and it was also said in this article that the tissue was taken from her after her death, and so from this article on this was like one of the first articles about Henrietta and the fact that they were her cells. Henrietta Lax would be changed to Helen Lane or Helen Larsen, leaving her family in the dark about the existence of her cells. But even if the Lax family didn't know about the cells and their connection to them, many researchers did, and they would soon be knocking at the door. By nineteen sixty six, HeLa cells had been in use in all kinds of research for fifteen years, and cell culture technology had also greatly advanced, with the isolation of many other different cell lines. But then came what I think in the book was referred to as the HeLa bomb. In nineteen sixty six, it was suggested that many of the different human cell lines that scientists believe they had isolated and conducted research on were actually HeLa contaminated, meaning that HeLa had taken over them, meaning that they weren't what they had what they thought they were. Yeah, and so this, like I guess, vigorous quality of HeLa cells had long been known, but this massive takeover was on a whole other level because if this were true, that meant millions of dollars of research money and years of research were essentially wasted because they were done on cells with properties that may not have been there.
Right, Yeah, like you thought that you were working with kidney and you were working with HeLa exactly.
Yeah, But okay, first things. First, researchers were like, well, we need to get like a handle on the extent of this of the contamination that exists. And also we you know, and once we get that done, we want to find a way to better control contamination in the future. And so that you know, both of those things could be achieved by developing a test specifically for the presence of HeLa cells. To keep that in mind, we need to test specifically for HeLa cells.
Okay, yeah, not going to be good and no.
By the nineteen seventies, the misleading names of Helen Lane or Helen Larsen began to fall out of use as journalists and scientists began to set the record straight, with one person in a letter to Nature suggesting that it might be time to authenticate her name quote and let he Lah enjoy the fame she so richly deserves. So even though Henriette's real name and connection to the cells began to be widely known among the researchers who cultured her cells, the family still had no idea of their existence until nineteen seventy three when Bobbett, Lawrence's wife, met the brother in law of a friend of hers. And this brother in law of her friend worked at the NIH and when Babette mentioned that her last name was Lax, he was like, Oh, that's strange. I work with cells from someone named Henrietta Lax. And Bobbett was like, well, that was my mother in law's name, but she died twenty five years ago and he was like, Oh my gosh, that's whose cells I work with?
What?
And obviously this led to a lot of confusion for Bobbett, the news that this guy worked with her deceased mother in law cells and the fact that he ordered them quote just like everyone else, like right, how, which implied that there were people all over the country and even all over the world who had access to her deceased mother in law cells.
That's I can't even imagine how bizarre, right?
It felt like a violation or an invasion maybe, like just I mean, this was yeah, like in many ways, this seemed like like some sort of a nightmare, Like first they took Henrietta cells without asking, and it seemed likely, or at least possible, that next they would try to conduct non consensual research on her relatives, which was not an unfounded fear, because while discussing this problem of HeLa contamination, one of the scientists suggested that a lot of the headache could be resolved if they had genetic markers to test for the presence of HeLa cells, and one way to do that would be to test Henrietta's children as well as day lax. No problem, one of the doctors said, there's still patients at Johns Hopkins, so we can call them right up. And that's what they did. Yeah, according to the postdoc put in charge of collecting the blood from the Lax family, she called up the family and eplained that they wanted to draw some blood from the family members so that they can develop these genetic markers. But according today, what they said was that they wanted to test for the same cancer that Henrietta had and her children. Oh dem And so they agreed and blood was drawn. Did anyone attempt to obtain informed consent?
No?
Did anyone fill out an IRB? No?
No.
And while those requirements were not yet finalized in the law, they were only months or days away from being finalized.
Oh my god.
And when Deborah asked Victor mccusick, who spearheaded this effort, about her mother and about her cells, he ticked off some things that they had helped to accomplish, like the polio vaccine, this genetic research, atomic bomb testing, et cetera. And then he handed her a book that he had edited called Medical Genetics. In that book, she found jargon filled sentences and a photo of her mother that no one had ever remembered providing and certainly had not given permission to print what yeah, And this was as far as he went to explain how her cells were still alive even though Henrietta had died, and why they had taken her cells, and how they had accomplished those things. And they certainly didn't tell Deborah any cancer results because they weren't testing for cancer, of course, of course not. They left the Lax family with way more questions than they attempted to answer, and over the next few decades the answers would be slow to come. A reporter for Rolling Stone named Michael Rogers, who was one of the first, if not the first reporters to contact the Lax family about Henrietta, published an article that led to many other reporters and people knocking on their door, some well intentioned, others very much not, but overall well over time, this narrative was shifting from what have these cells been used to accomplish? To what does informed consent mean? What rights does a person have over their body? How can patient privacy be insured, especially in this age of genetic research? Can genes be patented? And finally, after all this time, who was the person from whom these cells were taken, and many people have worked to raise awareness about Henriette A. Lax and her story, especially her family and also Rebecca Sclute, who wrote the book The Immortal Life of Henriette A. Lax. And Henrietta's story is still invoked in discussions of how race intersects with informed consent and tissue research and patient privacy. Some institutions and companies that have profited off Henrietta cells are finally donating money as a small step towards acknowledging her contribution, and Henrietta's legacy extends far beyond the scientific and medical advancements that her cells helped to achieve. There is now the Henrietta Lax Foundation, which provides quote financial assistance to individuals and families, particularly within minority communities, who were involved in historic research cases without their knowledge, consent, or benefit. This includes the cases of Henrietta Lax and HeLa cells, the Tuskegee syphilis studies, and the human radiation experiments, among others. In addition, several institutions have awarded Henrietta honorary doctorates. There are plans for a JOHNS. Hopkins research building to be named after her. She's now in the National Women's Hall of Fame. Her name has been tied to laws protecting participants in clinical research trials. There are plays and songs about her. I mean, the list could go on forever, just like hersels So Aaron, even though I feel like I went on forever, there's so much I didn't cover, and I'm very excited to hear what you're going to tell me about what HeLa cells and what informed consent and tissue culture research is up to today.
Oh, I can't wait to tell you. We'll take a quick break first. There have been over one hundred and ten thousand research articles published using HeLa cells.
That's estimated incredible.
Three Nobel Prizes have been awarded for work with HeLa cells, most recently in twenty fourteen for the development of advanced microscopy techniques that allow you to view cellular growth like live while telling and like we kind of mentioned many times already, HeLa cells have been used for literally everything that you can imagine, from the study of virology to cancer therapeutics, drug delivery systems, basic cellular functions, cell signaling, everything, everything. There's a visual that I'll link to that I think kind of gives you a little bit of a clue of just like the array of topics and just how many there are. But literally everything that we do in biology has been done on HeLa cells.
It's incredible.
It's incredible. We have come amazingly far in the last seventy years in terms of our understanding not only of cellular development and molecular biology, but also in our ability to use this knowledge for therapeutics, for vaccines, things that we talked about in so many previous episodes this season and in previous seasons, like in our Huntington's Disease episode when we talked about developments in gene therapy and the potential for something like Crisper to change the game when it comes to genetic diseases. This is only possible because of in vitro cell lines. We have made immense strides in developing specific targeted cancer treatments like monoclonal antibodies. We've also developed treatments for things like even covid and other infectious diseases.
That's amazing.
We are getting better and better at developing cell lines, both from human cells but also animal cell lines to produce very specific proteins and antibodies that are closer and closer to you, exactly like a very targeted type of structure that we want to produce. It's really difficult to over I don't think it's possible to overstate the impact that these cells have had. No.
I think it's it's probably like one of the biggest things in biomedical research.
History, right right, so many things. So another future foray that we've touched on in the past in our organ transplantation episode is the development of induced pluripotent stem cells. Okay, so let's talk about this a little bit. Pluripotent stem cells are like embryonic stem cells, they can become any type of cell. But induced pluripotent stem cells means that you take cells from like a grown human, like a full adult human or a kid, but a fully differentiated cell, and using things that are too complicated for me to fully understand and talk about, but including tilomerace, you can cause these cells to revert back to being stem cells. We have the technology to do this today, and this means that not only can you develop an immortal cell line from any person cells, but you can develop stem cells from any individual cells, which means that those cells could then be induced to differentiate into any other cell type. That type of technology, combined with technology to grow cells in three dimensional structures, it's the exact type of technology that makes it even imaginable to someday be able to grow entire human organs, which could change the game when it comes to treatment of chronic and currently uncurable diseases. And even though we don't have that technology right now, the fact that it's even something that we can dream about is only possible because of HeLa cells, because of Henrietta Lacks. Yeah, yeah, it's it's hard to even like put into words how influential this has been, Like it's yeah, yeah, but even though that's hard to put into words, just how influential in terms of scientific achievements HeLa cells have been. Like you mentioned a lot Aarin, we have to recognize what a massive kind of ethical issue has arisen because of this. Not only was it using cells without her permission, it was also identifying these cells as belonging to her, thereby releasing information about her and her family members without their knowledge or permission.
Right.
And the thing is, like you kind of alluded to Aarin, we really haven't completely fixed the system to ensure that this could never happen again.
Not at all. It's very like alarming.
Yes, So currently the common Rule, that's what it's called. It's the code from the Department of Health and Human Services that details the protection of human subjects, basically laying out the requirements for RB, institutional review board review, and everything that pertains to the ethics of human subjects. Research in the United States at this point in time still allows for the use of biospecimens without informed consent so long as they are deidentified. So no longer can you take a cell and call it HeLa, thereby knowing that it came from Henrietta Lax. But you could take a tissue sample from someone, slap on a number that isn't like their medical record number, but is just some their number, and thereby make it deidentified so it has no association with them without ever telling them. The problem is, yeah, that that is not keeping up with the times today. You could sequence a genome from that cell and have all of that genetic information, and especially when you think of how many people swab their cheeks and then send in their DNA to be sequenced to all of these different companies. Then you have that information and can compare it across these databases. In light of how much technology has progressed, that type of allowance for allowing the use of biospecimens without informed consent, it's problematic. There are some new regulations that have come into play that say that if there is going to be any genomic innunalysis of human data, then you do have to obtain informed consent. But that's still just one piece of it. So really, this is even though this was last reviewed in twenty seventeen, which wasn't that long ago. Yeah, it's still out of date at this point.
I mean, like, we know that technology moves faster than ethics, ethics and laws, but like this isn't the writing has been on the wall right for a very long time. It was more than on the wall in twenty seventeen.
Exactly exactly. Yeah, I think, you know. The good thing is so twenty twenty was Henrietta LAX's one hundredth.
One hundredth anniversary of the day she was born.
Right, And so I think that, you know, because of that, there was like a large amount of celebration because of that, And I think that more and more we are having these conversations, right, But like you said, Aaron, people are only just now barely beginning to actually put their money where their mouth is, both literally and figuratively, to make substantial change in the way that we deal with ethics in human research studies. There have been two or three institutes in the US and the UK that have made either a single large donation or have committed to make donations to the Henrietta Lax Foundation every time that they develop new cell lines from HeLa cells. The head of NIH also got a large grant and is donating a portion of it to the foundation. So people are kind of just finally starting to recognize that because of the impact that these sales have had, like there needs to be reparations back essentially for sure. Yeah, but it's still not nearly at the point yet that it needs to be no, right, but it's at least a start.
It's a start. It's a start, just a delayed start.
Yeah.
So we wanted to make this episode in large part just to kind of get this story more press so that people can really hear about it, and a lot of people have asked for us to cover it. But we also wanted to put our money where our mouth is So we also made a donation to the Henry Lax Foundation. Yeah, so small step, but a step nonetheless a step.
Yeah.
So with that sources sources.
My source list was very short for this episode. Primarily I use the Immortal Life of Henrietta Lax by Rebecca Sclute and a few articles here and there that I will post on our website. I'm jealous, Aaron, I have a long list of articles because I had to learn all about you know, tulamers and things. But I'll post the full list of all of the sources that I used if you want to learn more about the cell cycle and cell lines and also what we use HeLa cells for today and kind of the future of cell culture and cell lines. On our website This podcast will Kill You dot com under the episodes tab, you can find the fullest of our sources for this episode and every single one.
Of our episodes.
Yes, thank you to Bloodmobile for providing the music for this episode and all of our episodes.
Thank you to the Exactly Right Network, of whom we are extremely proud to be a part.
And thank you to you listeners for listening. Yeah for recommending this episode.
Yeah, we hope that it lived up to your hopes and dreams and expectations.
Yeah, well, until next time, wash your hands.
You filthy animals.
Obe o b u b o o b
