Rebecca Skloot tells the gripping, tragic, and fateful story of how HeLa cells came to be. The book is divided into three parts. In the first part, we learn about Henrietta Lacks, the patient who was the source of HeLa cells (so named because they represent the first two initials of her first and last names). In the second part, we learn about the incredible scientific opportunities that HeLa cells opened up for researchers. In the third part, we learn about the terribly difficult circumstances of the family of Henrietta Lacks, and the impact HeLa cells had upon them.
Henrietta Lacks was a poor African American woman who was diagnosed with cervical cancer in 1951 at Johns Hopkins Hospital. The surgeon on duty, Dr. Lawrence Wharton Jr., was preparing to insert a tube with radium into Henrietta's cervix to treat her cancer. While she was unconscious, Dr. Wharton cut out two dime-size chunks from her cervix and sent them to Dr. George Gey, who was trying to figure out how to grow cells in the laboratory, outside of an organism.
Although Dr. Gey had tried and failed at this many times, for some unknown reason Henrietta's cells would be different from all of the others, and would in fact thrive in a laboratory culture dish. Although she never consented to this tissue donation, she provided the material that initiated the field of tumor cell culture.
Eerily Divergent Paths
Rebecca Skloot describes the eerily divergent paths taken by Henrietta's body and her cervical cancer cells. While one struggled against disease and poisonous radium therapy, ultimately succumbing to death within a short time, the other grew, expanded, thrived and spread throughout the world.
In Part 2 of the book, Skloot describes how HeLa cells were used to mass produce a polio vaccine, to develop reliable cell culture and cell storage methods, to develop clonal cell lines, to visualize human chromosomes, and to test new drug candidates, among many other breakthroughs.
We also learn about how the name Helen Lane was disseminated to hide the true identity of Henrietta Lacks, a misunderstanding that persists to this day among many researchers. We also learn about the cavalier attitude of some physicians in this era, and specifically how a virologist named Chester Southam deliberately injected, without any consent, patients as well as Ohio state prisoners with HeLa cells to see if they would form tumors in people—something that would be inconceivable today.
In fact, Southam only stopped his human experiments when three physicians working for him at the Jewish Chronic Disease Hospital refused to inject their patients without consent because they believed it violated the Nuremberg Code, established after the Nazis experimented on prisoners in concentration camps during World War II.
Finally, in Part 3, we see the Lacks family up close through the eyes of the author, when she described her extensive interactions with the family in an attempt to learn about the effect of their mother's death and HeLa cells on the family.
In this tragic and touching conclusion to the story, we learn how Henrietta's adult daughter is driven to paranoia and anxiety because of her inability to understand what has become of her mother's cancer cells. Her lack of comprehension of the biomedical research they are a part of leads her to believe her mother has been cloned, experimented upon, and sent into space, despite having been dead for nearly 50 years at the time.
We see the warmth and spirituality of the family as they try to support each other and learn what has become of HeLa cells, and the missed opportunities as researchers and physicians fail to make even a passing attempt to explain the role of Henrietta's cells in biomedical research.
In summary, this beautifully written book tells the story about the stunning impact one cervical cancer patient had upon the world of science, and the complex interconnectedness of patient consent, science education, and human subjects research. Hopefully it will spark a greater discussion of the role of tissue donors and informed consent in biomedical research.
So many of us have benefited from HeLa cells; let us hope that by telling their story, Skloot will provide the family of Henrietta Lacks the honor they deserve.
Brent Stockwell is also the son of OT Editor Serena Stockwell
Just One Example of the Tremendous Power & Opportunity Made Possible with HeLa Cells
My first encounter with the HeLa tumor cell line was in 1996 as a graduate student working in Stuart Schreiber's laboratory at Harvard University, collaborating with Marta Muzio, a postdoc in Vishva Dixit's laboratory at the University of Michigan. Part of my doctoral thesis involved designing small molecules that could bring together, dimerize, two different proteins. Marta and Visha were interested in applying this method to the study of apoptosis, which had only recently been elucidated and was generating an enormous amount of excitement in the biomedical community. Indeed, Bob Horvitz, a professor at MIT who discovered the caspases, key proteins regulating apoptosis in the nematode C. elegans, would go on to win the Nobel Prize for this work in 2002.
Marta, Visha, and I worked together to design variants of the pro-death protein caspase-8, that could be activated with a small molecule dimerizer. It was known that caspases were the executioners of apoptosis—that is, once a cell received a signal to die through apoptosis, these caspase proteins would be turned on and would dismantle the crucial structural and functional proteins within the cell, leading finally to death of the cell. The crucial question that everyone wanted to know was, how are these caspases activated—that is, how, in a biochemical sense, are they turned on by a pro-apoptotic signal?
Marta and Visha suspected that these caspases were turned on by dimerization. It was known that caspases are made by the cell in an inactive form, known as a zymogen—which needed to be cut open by another protease in order to liberate the active form of the caspase, akin to the metamorphosis of a caterpillar into a butterfly.
Nobody knew what this mysterious protease was that could activate pro-caspase-8. Visha and Marta speculated that it was pro-caspase-8 itself—In other words, they thought that the “inactive” form of the caspase actually had a small amount of residual activity. Working with Guy Salvesen and Henning Stennicke at the Burnham Institute, they went on to show this was true They imagined that if the zymogen form of caspase-8 had a small amount of protease activity, that bringing two of these molecules together and forcing them to be directly adjacent would then allow each one to cut open the other, liberating activate caspase-8 and turning on the apoptosis cascade.
This is where the HeLa cell line enters the story. With a biochemical hypothesis like this, it is very difficult to test the mechanism directly in an animal model. The use of isolated cells in a dish in the lab makes it far easier to probe such mechanistic questions.
HeLa cells represented the first isolated cell line, and opened up the possibility of doing hundreds of thousands of these kinds of mechanistic experiments. In fact, we tested the dimerizer hypothesis with caspase-8 in HeLa cells,1 and found that dimerizing the zymogen form of caspase-8 would indeed activate apoptosis. This single event was sufficient to turn on the suicide program in these cells.
This is just one isolated example of the tremendous power and opportunity that HeLa and other tumor cell lines have brought to biomedical science.
The Story Behind the Book: An Interview with Author Rebecca Skloot
BY RABIYA S. TUMA, PHD
In her book, The Immortal Life of Henrietta Lacks, Rebecca Skloot reveals the long untold story of the woman behind HeLa cells, the first immortalized human cell line. In this interview with OT, in mid-February, Skloot shares how she came to spend more than 10 years working on the book and what she thinks is likely to come from it.
Did you have any expectation that there would be this amount of enthusiasm about the book?
As a writer, you're not really allowed to think this might happen, that people might get really excited about the book and that it might get so much press.
But at the same time, it doesn't surprise me at all because the things that people are responding to are the same things I responded to when I first heard the story. The facts of the story are just amazing. Every time I would talk about it either at an event or at a dinner party, the reactions people had were so strong.
Many of us heard reference to Henrietta Lacks (or Helen Lane—a pseudonym name once ascribed to the patient) in biology class. What made you need to know more about the woman behind the cell line?
A lot of things. One of them, the basic story of learning about HeLa in biology class is in the book.
But also when I was sixteen, my dad was pretty sick. He had just recently come down with this weird viral infection that nobody really knew what was wrong with him, and it caused some pretty severe brain damage. He had gone from being my normal dad—a marathon runner—to being somebody who could barely walk. The same year that I found about HeLa cells, he had enrolled in an experimental drug study. He couldn't drive because of the brain damage, so I would drive to and from the hospital where he was getting these infusions—We didn't know if it was the drug or the placebo. He and a lot of other people were getting these infusions and in the end there were some questions about the study ethically. People had been promised they would get the drug if it seemed to work and then this or that fell apart. So I was in the midst of watching my own father go through research and experiencing the hopes that can come with science, but also the frustration and fear that came along with it.
I think part of the reason I latched onto the story: Here I was this kid who was basically watching her own father be used in research. My first question when I heard about the HeLa cells was did she have any kids and what did they think about it.
As I was reading your book I was shocked over and over, by the way Lacks family members were treated over the years and by some experiments we would now deem unethical. When you look back over the research for the book, what was most shocking for you?
In a lot of ways, it was the chapter where we learned about Henrietta's daughter Elsie in Crownsville, the mental institution where she had been hospitalized. I was prepared to hear about research being done on Henrietta's tissues and her kids’ tissues. I knew there was a lot of research done on the family without their knowledge. But the stuff that was done to Henrietta's daughter—they were drilling holes in her head and inserting metal probes, and they were doing some stuff that was painful and invasive—that was pretty shocking to just happen upon. Especially in the context of the Lacks's larger story, which is a story of a family used again and again in research without their knowledge.
Some of the responses from researchers were pretty surprising. I mean there was the researcher who did research on Henrietta's kids in the ‘70s. I told her that the family thought they were being tested for diseases and potentially treated, not that they were being used in research. She was shocked and she said they never would have told them they were testing them for anything. But then she asked me if I could put her in touch with the family so she could get more blood samples. I was a little surprised by that.
What was the most damaging aspect, do you think, for the Lacks family?
It depends on whom you talk about. With Deborah, Henrietta's daughter, in a lot of ways the most damaging thing was this lack of understanding of what was going on, and the fact that no one told her anything even when she asked. They would do things like giving her a medical school textbook to read when she couldn't read at all. She just wanted to understand what was going on with her mother and her mother's cells, and the stuff she was hearing from scientists was really scary: Oh we sent her cells up to the moon; we injected them with all these chemicals, and we fused her DNA with mouse DNA.
It all had this very scary sci-fi quality to it, so she had a very hard time distinguishing what was reality and what wasn't when it came to science. And she was very worried that some of the stuff they were doing to her mother hurt her somehow. Like if they are shooting her mother's cells up to the moon, can she rest in peace? For her, it was more these existential questions that were really damaging.
For her brothers, a lot of it was the money issue and the insult that they felt: “Here we are always hearing that our mother's cells are so important to science and made all this medicine possible, but yet we don't have access to it because we can't afford it.” A lot of their anger came from that.
Do you think the book is recognition enough or do you think something else should be done by the science community itself?
I think my job is to put the story out there. I think there is probably going to be a discussion about whether the family deserves some recognition or what sort of regulations should be put in place to regulate the way tissue research is done now.
The Lacks family certainly believe they deserve something from somebody.
I set up a foundation, the Henrietta Lacks Foundation, where some of the proceeds of the book are going. My goal with it is a scholarship fund that will help the descendants of Henrietta Lacks go to school and potentially get health insurance. Some of that depends on how much I end up getting in there.
Have other people been contributing to that?
It is starting to trickle in. No big donations or anything like that, but it is interesting that the donations range from a dollar to, I think, so far the biggest one is $250. But this is the general public who is reading and responding to the book, and maybe some scientists who used her cells and feel like they want to do something for the family.
But a large pharmaceutical company or the American Type Culture Collection, for example, haven't stepped up and said ‘Here is a check’?
Do you expect that someone, not necessarily those two, but some research body will?
The ATCC is a nonprofit. They respond very powerfully to this. They have said many times that they did not profit off of this, that they are a nonprofit and the money goes back into science. But there are a lot of for-profit companies that do. It will be interesting to see how they respond, I really don't know.
I think there is a big concern from scientists that to do anything for the family would be setting a precedent. There is a lot of concern that this sort of idea of patients’ rights, when it comes to tissues, will interfere with scientific research and that people will hold out for profits or something like that.
I don't think that is a danger at all. I have talked to people who have been involved in every case that has gone to court related to this, and though the lawsuits often end up being about money, the initial anger from the people involved is that things were happening that they weren't told about.
Across the board, they said to me “If they had just asked, we would have said yes. And if they had asked and said there was a chance that it was going to be commercialized, we still probably would have said yes. But the fact that they didn't tell us…” This is where you end up in the courts, when people feel like they have been deceived.
I think probably the movement will be towards consent and the money issue will probably not be the center of attention. But I think it is because of that concern there isn't any kind of big companies rushing to donate money.
From your afterward on tissue banking and cell culture laws, it really sounds like the same thing could happen today but without the name attached to it.
It happens every day. Pretty much everybody in the US has their tissues on file somewhere. Although we don't realize it, a lot of us have signed consent forms. When you go in for a biopsy, it says “You can dispose of my tissues any way you see fit or use them in research.” People don't realize what that means or that it could become commercialized.
There is no standard practice when it comes to consent. In some cases they give people these big thick brochures that are almost like books explaining all of this, then at the other end of the extreme is the thing that just says you can dispose of my tissue however you want. It certainly isn't informed consent across the board.
There is no real requirement for it. Most of the federal guidelines governing research on human subjects don't apply to tissue research because either the identity is stripped or the researcher didn't have contact with the person first hand, so it is not considered human research.
Do you think twice when you go to the doctor and have blood drawn or what not?
I don't because I know what is going to happen with it, and I am fine with that. I think that is what it really comes down to in a lot of cases—it is just information. Of course most people want to help science. We all know that we benefit from this stuff, we want this research to happen.
Would you like to see consent be a more active process, an education process?
The first step is that it needs to be an upfront process. There needs to be more transparency in what is going on, in terms of telling people what it means to say “you can get rid of my tissues.” I think it needs uniformity.
I also think it is not my job to say this is what should happen with regulation. My job has been to put the story out there. People are responding to that and saying we need to make this a bit more uniform and address these big questions.
Scientists are not necessarily in favor of that. A lot of scientists fear that will inhibit research in some way. People often point to the fact that your name is not on there so it is a non-issue, but science is at a place now where it is technically possible to find an identity using DNA.
When they took Henrietta's cells in the ‘50s, no one could imagine that someday you would be able to look at those cells and learn something about her kids and grandkids. So what are we going to be able to learn in 20 years from these samples we now think of as anonymous? It is not much of a stretch to think that in much less than 20 years, we are going to be able to learn a lot more about some of these samples than we think we can now.
So some of it is looking at the Lacks's story as a way to say, “Okay here is how much can change in a very short period of time and we're still not clear on how to handle the ethical issues”—even though it is pretty clear that things are going to evolve just as fast, if not faster from here.
You cover an enormous amount of ground in the book, from a very personal biography to the history of science and tissue culture. Did you have any idea you were going to be spread that far when you started the project?
Not really. In part because I had no idea what had happened to her family when I started. I thought this was going to be a story of the woman and the cells. I did think it was going to be the story of the evolution of the science and the ethics, but I had no concept of the role that the family's story would play. Or that I would be in it at all.
I was very resistant to the idea of being in the book at all—I actually find it annoying when writers insert themselves into books where they don't belong. But then it became very clear to me that part of the story was about all of these journalists and other people who had been coming to her family over all the years wanting something from them and I was another one of those people in a sense. My presence in their life had some pretty dramatic effects on them at various points, and I thought it would be sort of dishonest to leave that out.
Oncology Times goes to practicing physicians and researchers. With that audience in mind, is there a take-home message or messages that you think readers should learn from this story?
Yes, I think there are a lot of them. One is the idea that there are people behind every one of the billions of biological samples that we all use in research every day. I cannot tell you the number of emails I've gotten from researchers who say that they heard me talking on the radio or read the book and had this very powerful reaction of saying ‘Oh my god, I had no idea. I owe a lot of my career to these cells, and I never even wondered where they came from, or whether she had given consent or whether her family cared.’ These are questions that scientists don't often think about.
Also you often hear scientists say that they are unhappy with the level of regulation, the IRBs and all the paper work and stuff we have to do to get research done. In the book you find out why you have to do that. And why it is important. I think those are important take-home messages.
I also think it is important for scientists to know that I was very aware of wanting this to tell both sides of the story fairly. This is not a story that demonizes scientists. In some ways it is setting the record straight about some scientists who had been demonized for a long time. This story has been held up for many years as one of a racist scientist who stole these cells from this black woman. But that is not what happened. I tried to make it clear on both sides that there are human beings behind everybody in this story and how complicated science is.
Anything else you would like to say for this audience?
For the most part, scientists have been really receptive to the book. There has definitely been some of them who have read about the book in the media and had very strong reactions to it, saying ‘This is ridiculous. The family is obviously just campaigning for money’ and really dismiss the idea of the story being an important one, without knowing the story behind it.
I think there is a way in which this story is different from what anyone thinks it is, both on the side of the scientists and on the side of the general public. Anyone who has known about the story, on either side, is surprised by what they actually find.
I am really happy you are doing this. I am doing a tour between now and June talking about the book. My favorite audiences are the scientists. For scientists this is a very personal story. Many describe the idea of reading the book and then going into their lab afterwards and feeling like their labs are almost haunted now.
HeLa cells are everywhere, and that means Henrietta is everywhere. Scientists have a different take on it. Some of them are very sympathetic to the family. Some of them aren't. But the fact that they have some sort of personal relationship to the cells already is an important part of the whole story.
For More Information
A schedule of Rebecca Skloot's readings can be found at Rebeccaskloot.com/events, and more information about the Henrietta Lacks Foundation can be found at henriettalacksfoundation.org