Henrietta Lacks' Cells Enabled Medical Breakthroughs. Is It Time to Finally Retire Them?
For Victoria Tokarz, a third-year PhD student at the University of Toronto, experimenting with cells is just part of a day's work. Tokarz, 26, is studying to be a cell biologist and spends her time inside the lab manipulating muscle cells sourced from rodents to try to figure out how they respond to insulin. She hopes this research could someday lead to a breakthrough in our understanding of diabetes.
"People like to use HeLa cells because they're easy to use."
But in all her research, there is one cell culture that Tokarz refuses to touch. The culture is called HeLa, short for Henrietta Lacks, named after the 31-year-old tobacco farmer the cells were stolen from during a tumor biopsy she underwent in 1951.
"In my opinion, there's no question or experiment I can think of that validates stealing from and profiting off of a black woman's body," Tokarz says. "We're not talking about a reagent we created in a lab, a mixture of some chemicals. We're talking about a human being who suffered indescribably so we could profit off of her misfortune."
Lacks' suffering is something that, until recently, was not widely known. Born to a poor family in Roanoke, VA, Lacks was sent to live with her grandfather on the family tobacco farm at age four, shortly after the death of her mother. She gave birth to her first child at just fourteen, and two years later had another child with profound developmental disabilities. Lacks married her first cousin, David, in 1941 and the family moved to Maryland where they had three additional children.
But the real misfortune came in 1951, when Lacks told her cousins that she felt a hard "knot" in her womb. When Lacks went to Johns Hopkins hospital to have the knot examined, doctors discovered that the hard lump Henrietta felt was a rapidly-growing cervical tumor.
Before the doctors treated the tumor – inserting radium tubes into her vagina, in the hopes they could kill the cancer, Lacks' doctors clipped two tissue samples from her cervix, without Lacks' knowledge or consent. While it's considered widely unethical today, taking tissue samples from patients was commonplace at the time. The samples were sent to a cancer researcher at Johns Hopkins and Lacks continued treatment unsuccessfully until she died a few months later of metastatic cancer.
Lacks' story was not over, however: When her tissue sample arrived at the lab of George Otto Gey, the Johns Hopkins cancer researcher, he noticed that the cancerous cells grew at a shocking pace. Unlike other cell cultures that would die within a day or two of arriving at the lab, Lacks' cells kept multiplying. They doubled every 24 hours, and to this day, have never stopped.
Scientists would later find out that this growth was due to an infection of Human Papilloma Virus, or HPV, which is known for causing aggressive cancers. Lacks' cells became the world's first-ever "immortalized" human cell line, meaning that as long as certain environmental conditions are met, the cells can replicate indefinitely. Although scientists have cultivated other immortalized cell lines since then, HeLa cells remain a favorite among scientists due to their resilience, Tokarz says.
"People like to use HeLa cells because they're easy to use," Tokarz says. "They're easy to manipulate, because they're very hardy, and they allow for transection, which means expressing a protein in a cell that's not normally there. Other cells, like endothelial cells, don't handle those manipulations well."
Once the doctors at Johns Hopkins discovered that Lacks' cells could replicate indefinitely, they started shipping them to labs around the world to promote medical research. As they were the only immortalized cell line available at the time, researchers used them for thousands of experiments — some of which resulted in life-saving treatments. Jonas Salk's polio vaccine, for example, was manufactured using HeLa cells. HeLa cell research was also used to develop a vaccine for HPV, and for the development of in vitro fertilization and gene mapping. Between 1951 and 2018, HeLa cells have been cited in over 110,000 publications, according to a review from the National Institutes of Health.
But while some scientists like Tokarz are thankful for the advances brought about by HeLa cells, they still believe it's well past time to stop using them in research.
"Am I thankful we have a polio vaccine? Absolutely. Do I resent the way we came to have that vaccine? Absolutely," Tokarz says. "We could have still arrived at those same advances by treating her as the human being she is, not just a specimen."
Ethical considerations aside, HeLa is no longer the world's only available cell line – nor, Tokarz argues, are her cells the most suitable for every type of research. "The closer you can get to the physiology of the thing you're studying, the better," she says. "Now we have the ability to use primary cells, which are isolated from a person and put right into the culture dish, and those don't have the same mutations as cells that have been growing for 20 years. We didn't have the expertise to do that initially, but now we do."
Raphael Valdivia, a professor of molecular genetics and microbiology at Duke University School of Medicine, agrees that HeLa cells are no longer optimal for most research. "A lot of scientists are moving away from HeLa cells because they're so unstable," he says. "They mutate, they rearrange chromosomes to become adaptive, and different batches of cells evolve separately from each other. The HeLa cells in my lab are very different than the ones down the hall, and that means sometimes we can't replicate our results. We have to go back to an earlier batch of cells in the freezer and re-test."
Still, the idea of retiring the cells completely doesn't make sense, Valdivia says: "To some extent, you're beholden to previous research. You need to be able to confirm findings that happen in earlier studies, and to do that you need to use the same cell line that other researchers have used."
"Ethics is not black and white, and sometimes there's no such thing as a straightforward ethical or unethical choice."
"The way in which the cells were taken – without patient consent – is completely inappropriate," says Yann Joly, associate professor at the Faculty of Medicine in Toronto and Research Director at the Centre of Genomics and Policy. "The question now becomes, what can we do about it now? What are our options?"
While scientists are not able to erase what was done to Henrietta Lacks, Joly argues that retiring her cells is also non-consensual, assuming – maybe incorrectly – what Henrietta would have wanted, without her input. Additionally, Joly points out that other immortalized human cell lines are fraught with what some people consider to be ethical concerns as well, such as the human embryonic kidney cell line, commonly referred to as HEK-293, that was derived from an aborted female fetus. "Just because you're using another kind of cell doesn't mean it's devoid of ethical issue," he says.
Seemingly, the one thing scientists can agree on is that Henrietta Lacks was mistreated by the medical community. But even so, retiring her cells from medical research is not an obvious solution. Scientists are now using HeLa cells to better understand how the novel coronavirus affects humans, and this knowledge will inform how researchers develop a COVID-19 vaccine.
"Ethics is not black and white, and sometimes there's no such thing as a straightforward ethical or unethical choice," Joly says. "If [ethics] were that easy, nobody would need to teach it."
A new type of cancer therapy is shrinking deadly brain tumors with just one treatment
Few cancers are deadlier than glioblastomas—aggressive and lethal tumors that originate in the brain or spinal cord. Five years after diagnosis, less than five percent of glioblastoma patients are still alive—and more often, glioblastoma patients live just 14 months on average after receiving a diagnosis.
But an ongoing clinical trial at Mass General Cancer Center is giving new hope to glioblastoma patients and their families. The trial, called INCIPIENT, is meant to evaluate the effects of a special type of immune cell, called CAR-T cells, on patients with recurrent glioblastoma.
How CAR-T cell therapy works
CAR-T cell therapy is a type of cancer treatment called immunotherapy, where doctors modify a patient’s own immune system specifically to find and destroy cancer cells. In CAR-T cell therapy, doctors extract the patient’s T-cells, which are immune system cells that help fight off disease—particularly cancer. These T-cells are harvested from the patient and then genetically modified in a lab to produce proteins on their surface called chimeric antigen receptors (thus becoming CAR-T cells), which makes them able to bind to a specific protein on the patient’s cancer cells. Once modified, these CAR-T cells are grown in the lab for several weeks so that they can multiply into an army of millions. When enough cells have been grown, these super-charged T-cells are infused back into the patient where they can then seek out cancer cells, bind to them, and destroy them. CAR-T cell therapies have been approved by the US Food and Drug Administration (FDA) to treat certain types of lymphomas and leukemias, as well as multiple myeloma, but haven’t been approved to treat glioblastomas—yet.
CAR-T cell therapies don’t always work against solid tumors, such as glioblastomas. Because solid tumors contain different kinds of cancer cells, some cells can evade the immune system’s detection even after CAR-T cell therapy, according to a press release from Massachusetts General Hospital. For the INCIPIENT trial, researchers modified the CAR-T cells even further in hopes of making them more effective against solid tumors. These second-generation CAR-T cells (called CARv3-TEAM-E T cells) contain special antibodies that attack EFGR, a protein expressed in the majority of glioblastoma tumors. Unlike other CAR-T cell therapies, these particular CAR-T cells were designed to be directly injected into the patient’s brain.
The INCIPIENT trial results
The INCIPIENT trial involved three patients who were enrolled in the study between March and July 2023. All three patients—a 72-year-old man, a 74-year-old man, and a 57-year-old woman—were treated with chemo and radiation and enrolled in the trial with CAR-T cells after their glioblastoma tumors came back.
The results, which were published earlier this year in the New England Journal of Medicine (NEJM), were called “rapid” and “dramatic” by doctors involved in the trial. After just a single infusion of the CAR-T cells, each patient experienced a significant reduction in their tumor sizes. Just two days after receiving the infusion, the glioblastoma tumor of the 72-year-old man decreased by nearly twenty percent. Just two months later the tumor had shrunk by an astonishing 60 percent, and the change was maintained for more than six months. The most dramatic result was in the 57-year-old female patient, whose tumor shrank nearly completely after just one infusion of the CAR-T cells.
The results of the INCIPIENT trial were unexpected and astonishing—but unfortunately, they were also temporary. For all three patients, the tumors eventually began to grow back regardless of the CAR-T cell infusions. According to the press release from MGH, the medical team is now considering treating each patient with multiple infusions or prefacing each treatment with chemotherapy to prolong the response.
While there is still “more to do,” says co-author of the study neuro-oncologist Dr. Elizabeth Gerstner, the results are still promising. If nothing else, these second-generation CAR-T cell infusions may someday be able to give patients more time than traditional treatments would allow.
“These results are exciting but they are also just the beginning,” says Dr. Marcela Maus, a doctor and professor of medicine at Mass General who was involved in the clinical trial. “They tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease.”
Since the early 2000s, AI systems have eliminated more than 1.7 million jobs, and that number will only increase as AI improves. Some research estimates that by 2025, AI will eliminate more than 85 million jobs.
But for all the talk about job security, AI is also proving to be a powerful tool in healthcare—specifically, cancer detection. One recently published study has shown that, remarkably, artificial intelligence was able to detect 20 percent more cancers in imaging scans than radiologists alone.
Published in The Lancet Oncology, the study analyzed the scans of 80,000 Swedish women with a moderate hereditary risk of breast cancer who had undergone a mammogram between April 2021 and July 2022. Half of these scans were read by AI and then a radiologist to double-check the findings. The second group of scans was read by two researchers without the help of AI. (Currently, the standard of care across Europe is to have two radiologists analyze a scan before diagnosing a patient with breast cancer.)
The study showed that the AI group detected cancer in 6 out of every 1,000 scans, while the radiologists detected cancer in 5 per 1,000 scans. In other words, AI found 20 percent more cancers than the highly-trained radiologists.
Scientists have been using MRI images (like the ones pictured here) to train artificial intelligence to detect cancers earlier and with more accuracy. Here, MIT's AI system, MIRAI, looks for patterns in a patient's mammograms to detect breast cancer earlier than ever before. news.mit.edu
But even though the AI was better able to pinpoint cancer on an image, it doesn’t mean radiologists will soon be out of a job. Dr. Laura Heacock, a breast radiologist at NYU, said in an interview with CNN that radiologists do much more than simply screening mammograms, and that even well-trained technology can make errors. “These tools work best when paired with highly-trained radiologists who make the final call on your mammogram. Think of it as a tool like a stethoscope for a cardiologist.”
AI is still an emerging technology, but more and more doctors are using them to detect different cancers. For example, researchers at MIT have developed a program called MIRAI, which looks at patterns in patient mammograms across a series of scans and uses an algorithm to model a patient's risk of developing breast cancer over time. The program was "trained" with more than 200,000 breast imaging scans from Massachusetts General Hospital and has been tested on over 100,000 women in different hospitals across the world. According to MIT, MIRAI "has been shown to be more accurate in predicting the risk for developing breast cancer in the short term (over a 3-year period) compared to traditional tools." It has also been able to detect breast cancer up to five years before a patient receives a diagnosis.
The challenges for cancer-detecting AI tools now is not just accuracy. AI tools are also being challenged to perform consistently well across different ages, races, and breast density profiles, particularly given the increased risks that different women face. For example, Black women are 42 percent more likely than white women to die from breast cancer, despite having nearly the same rates of breast cancer as white women. Recently, an FDA-approved AI device for screening breast cancer has come under fire for wrongly detecting cancer in Black patients significantly more often than white patients.
As AI technology improves, radiologists will be able to accurately scan a more diverse set of patients at a larger volume than ever before, potentially saving more lives than ever.