Taking cells from patients is a standard practice of biomedical research worldwide from the 50s till today. The first immortal cell line (HeLa cells) were created from cervical cancer cells taken from Henrietta Lacks, a young mother of five children died in 1951 at the age of 31 after seeking treatment at Johns Hopkins Hospital for an aggressive form of cervical cancer. Dr. Richard TeLinde, who treated Henrietta with radiation took a sample of her cervical cancer tissue without obtaining her permission and sent it to Dr. George Gey, the head of tissue research at the Johns Hopkins University School of Medicine (Skloot 2010). Gey found that HeLa cells were able to survive outside the body and reproduce rapidly which made them ideal for research and enabled researchers and scientists in worldwide to make great advances in science and medicine. The controversial past of Henrietta’s story is now more widely known because of Rebecca Skloot’s 2010 best-selling book ‘The Immortal Life of Henrietta Lacks’. The ethical issues interlinked with HeLa cells and medical research raised within the context of the book such as informed consent, privacy, compensation, experiments on black people, the legal battles over the control of genetic material, and also the enormous benefits and value of the growth of the HeLa cell line in cancer research will be discussed in this essay.
Ethical Questions That Arise Within the Context of the Henrietta’s Story
There are human beings behind every biological sample used in the laboratory and sometimes even with the best of intentions, things go wrong. Initially, taking cells from Henrietta and using them for research without her consent didn’t violate any legal standards, because the concept of informing or obtaining consent from the donors of cells did not exist in the 1950s. After Gey and his assistant found that Henrietta’s tumor cells were dividing and growing rapidly in the laboratory, he ordered his assistant, Mary Kubicek, to take more cells from Henrietta while her body lay in the hospital's autopsy room. Day, Henrietta's husband agreed to sign an autopsy permission form when Gey told him the tests they run may help the Lacks children someday. Gey was neither open nor honest; the truth is that none of their children could benefit from the tests as their mother’s cancer was not hereditary. He simply wanted to culture more cells from other parts of Henrietta's body. The rules have changed since then and they are still changing. According to the Australian National Health and Medical Research Council, participants of a clinical trial or research must give informed consent before taking part in the research; the consent form involves critical and essential elements of the process such as a detailed description of treatment and experimental procedures, purpose, duration, risks and benefits, nature of the illness, availability, confidentiality, subject’s rights and details of insurance coverage in case of injury.
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Geneticist Stanley Gartler discovered that HeLa cells with a genetic marker named G6PD-A found exclusively in black Americans had traveled on dust particles and contaminated other human cell lines. After the 70s, researcher Victor McKusick wanted to do genetic tests on Henrietta’s children to find out more about HeLa contamination and how to stop it. Her children were also then used in research without their consent, asked to give blood without explaining the motive and what he will do with the samples. With no given explanation, they assumed that the study was to test them for cancer that killed their mother. This caused extreme worry and unnecessary grief for all of Henrietta's children, who were never informed of the results of their cancer test which never happened.
The supreme court had determined that tissue removed from a patient no longer belongs to the patient and the doctor can dispose of the tissue any way he wants or use in research for the sake of medical progress. But researchers should respect the right for patients to make their own decisions and privacy wishes; not everyone has the same attitude about medical records as some people may more willing to share personal information than others. Henrietta was publicly identified as the source of HeLa cells when a team of scientists in the European Molecular Biology Laboratory (EMBL) sequenced the genome of HeLa cells and published their results in a public database (Sodeke et. al 2019). The Lacks family did not consent to release the information and this affected the privacy rights of the family members (Greely et al. 2013). “Future cures will come of this, but it needs to be handled in a way that protects people's privacy so people know what they're getting into when they donate. We aren't in a place where people understand what's happening” - said Skloot. Today researchers follow de-identified sampling and share limited personal information to protect the privacy of the donors.
Many of the benefits coming from tissue research aren’t available to those who provided samples for the research. Gey has never sold HeLa cells or profited from the discovery of them and never tried to patent them; he offered HeLa cells for scientific research to develop cures and save lives around the world (Skloot 2010). After Henrietta’s death, scientists freely and widely used her cells without permission from her family. Years later, Henrietta’s children accidentally learned that their mother’s cervical cancer cells were being used in researches which led to the creation of a massively profitable industry where their family didn’t have access to basic care back then. The book states Deborah’s word to Skloot, “But I always have thought it was strange, if our mother’s cells done so much for medicine, how come her family can’t afford to see no doctors? Don’t make any sense” (Skloot 2010, page 9). This proves that they lived in poverty and never received compensation or any of the financial benefits derived from their mother’s tumor cells.
The story of HeLa cells has often been described as one of the examples of patients and their families being mistreated because of the race. The Johns Hopkins Hospital where Henrietta Lacks was treated was one of the few hospitals that treated African American patients before the 1950s. However, black patients were treated in separated colored wards made of glass walls; there was no privacy at all and patient rights were ignored. They were not permitted to enter other parts of the hospital; even blood from whites and blood from black people did not cross the segregation line. When Henrietta was admitted to the hospital, her blood was taken, labeled ‘colored’ and stored in case she needed a transfusion. For many years white doctors and nurses treated black patients unwillingly, did not take care of them properly, and often ignored matters of patient privacy and basic human decency. Black people were not given a chance to question doctors, many black patients avoided going to the doctor until the situation was urgent; Henrietta was also often postponed going to the doctor because of the racism and classism she experienced there. TeLinde used patients from the colored ward for research because he thought that it was fair to use them as research subjects in exchange for free treatment offered them in the colored wards. However, patients never knew they were participating in research. Although TeLinde's urge to save lives and avoid unnecessary hysterectomies is commendable, using public ward patients without their permission is unethical.
According to Skloot, Henrietta was the first to know she is ill; after giving birth to her son Joe, she was continuously in pain and bleeding. When she felt a lump on her cervix, she went to the gynecological clinic at Johns Hopkins Hospital where Dr. Howard Jones took a biopsy of the lump and discovered that she has cervical cancer. Henrietta's pain was getting extreme and she believed her cancer was spreading and told her doctors about that several times, but they claimed that the pain was due to pregnancy and gonorrhea and nothing was wrong with her; but three weeks after they declared she is fine, and examining doctor found her cancer was indeed spreading and inoperable. The doctors did not give her pain medication until she was nearly dead and continued to give Henrietta radiation treatment to shrink her proliferating tumors and relieve her pain, but cancer got worsens and she passed away on October 4, 1951 (Rebecca Skloot, Part 1, Chapter 5).
Elsie’s treatment at Crownsville State Hospital was also an example of the mistreatment of black people at the hands of the medical profession. Henrietta was very emotional about leaving Elsie in an overcrowded hospital which was previously used as an insane asylum. Elsie has been diagnosed with 'idiocy which might be diagnosed as autism today as she was nonverbal and exhibits many of the signs of the disorder. She was also epileptic, and at the time treatments for epilepsy were still quite primitive. Skloot states that Henrietta and Elsie used to cry when they see each other. It is clear Elsie was deeply unhappy in the hospital; but when doctors said Elsie will be better off in the hospital, Henrietta did not question it. This incident reveals the poor treatment the Lacks family received because of their economic status and race.
Major Differences Between Normal Cells and HeLa Cells
Like many tumors, HeLa cells contain defective genomes with one or more copies of multiple chromosomes. The normal cell contains 46 chromosomes, while HeLa cells contain 76-80 chromosomes in total. Harald Zur Hausen, the scientist who discovered the HPV (Human Papilloma Virus), found that Henrietta developed cervical cancer due to particular mutations in her cells as a result of HPV-18 and HPV-16. He discovered that Henrietta's cells had multiple copies of the HPV genome in them contained several copies of HPV-18. HPV had inserted its DNA into the cells in Henrietta's cervix, the additional DNA results in the production of a p53-binding protein that prevents it from transforming and suppressing local p53 tumors and contributes to the changes in micro RNA expression. This discovery, however, did not explain why Henrietta's cells became so virulent and aggressive.
HeLa cells grow exceptionally fast, keeping track of their cancer status. This is because Hella cells grow easier and faster, doubling the number of cells in just 24 hours and making them ideal for large-scale testing. They grow so fast that they can infect and leave other cell cultures behind. Henrietta had syphilis, which caused suppression of the immune system and the aggressive growth of cancer cells. In 2013, it was shown that the scrambled HPV genome was inserted into the Henrietta genome near the c-myc proto-oncogene, which leads to its anatomical expression and rapid replication of HeLa cells. Lots of people had both HPV and syphilis at that time, but their cells were also not immortal as Henrietta’s.
Hela cells are immortal; this function can be explained by the expression of maximum telomeres. The early 1990s research on telomeres revealed an enzyme called telomerase in HeLa cells which allows cancer to regenerate itself; telomerase adds sequences at the end of chromosomes resulting undamaged and immortal cell. Although some cancer cells have active telomerase, they are not effective in comparison to HeLa cells particularly. HeLa cells gave researchers new clues about how to keep cancer from killing patients; this is an important step in figuring out how to stop cancer cells from spreading.
According to some scientists, the HeLa line was not the same as it had been when the first cells were cultured cell and no longer human at all. They also said that it should consider as a single-cellular organism that closely related to us, reproduces asexually through division and mutations that compound over time. However, Robert Stevenson, a researcher who helped to resolve the contamination ability of HeLa said “if someone took a sample from Henrietta's body today and did DNA fingerprinting on it, this DNA would match that in HeLa cells”. The debate over whether HeLa cells are still human reveals how deep the divide between scientists and their subjects can be. When people began talking more about Henrietta's legacy, scientists began to say the HeLa cells are not human. Robert Stevenson also said, “It’s much easier to do science when you disassociate your materials from the people they come from”. This disregard for human rights and for Henrietta as a human being reflects attitudes about race and class in medicine and in other fields.
Value of the Growth of the HeLa Cell Line in Cancer Research
Genetics has the power to transform cancer practice from prevention and early detection through treatment, this genetic knowledge comes from gene linkage studies or tumor specimen studies. Although many other cell lines are in use today, HeLa cells considered as ‘workhorse’ of cellular biology. HeLa cells have been used in studies of cancer cell migration and invasion, drug development benefiting hundreds of millions of patients. Cervical cancer is a global health problem, with more than half a million new cases a year (Sun et al. 2018). Harald Zur Hausen found out that by forcing its DNA into normal human cells, the HPV virus took control of the cell forcing them to produce various proteins associated with cancer. This proved to be one of the most important discoveries in that it allowed other scientists to use the knowledge to develop vaccines against the virus. Today, HPV vaccines help to protect young girls from the risk of HPV infections; according to statistics, the vaccine has reduced HPV by around 66% and prevented deaths associated with cervical cancer by about 70%.
However, despite the use of various therapeutic methods, more than one million women die each year from cervical cancer, making it life-threatening cancer and an urgent need for a therapeutic strategy. Clinical studies have shown that human papillomavirus (HPV) is the cause of cervical cancer; about 75% of fatal cervical cancers are associated with P5 dysfunction caused by HPV16. The HPV E6 gene product specifically interacts with the tumor suppressor protein p53 and acts as a potential trigger for its inactivation, with a high probability of developing cancer, as well as immortalization and transformation of cells. Therefore, the state of p53 is important for the growth, development, and treatment of cervical cancer.
Yoon et al. have shown that inhibition of TSC-22 mediated P5 proteasome degradation of H5V-positive HeLa successfully inhibits cell viability and induces apoptosis. Lee et al. found that vorinostat-induced acetylation of p53 can enhance doxorubicin-induced cytotoxicity in Hela cells. Another report demonstrated that cisplatin-induced apoptosis was independent of p53 in HPV-positive Hela. However, the inclusion of p53 in cervical cancer therapy, specifically in chemotherapy was controversial and required further clarification.
A study by Sun et al. investigated the functional roles of p53 over-expression in enhancing Lobaplatin (loba)-induced cell growth inhibition and apoptosis in cervical carcinoma cells. The results demonstrated that neither sub-lethal rAdp53 nor loba has any apparent apoptotic effect on Hela cells. The combination of rAdp53 and loba induced significant apoptosis and cell growth inhibition. P53 over-expression up-regulated the proapoptotic proteins Bax and Bak and xenograft cervical tumors derived from Hela cells demonstrated that co-treatment of rAdp53 and loba effectively inhibited tumor growth in vivo. The results of the study concluded that P53 restoration can sensitize cervical cancer cells to loba to induce apoptosis and cell growth inhibition.
Conclusion
Tissue culturing is not a bad thing, but there are challenges in how technology is used. Most of the advances in cancer research depend on tissue culture; we would have none of these if scientists were not collecting cells from people and growing them. Though HeLa cells were taken without consent from Henrietta, we cannot blame the doctors as during the 1950s taking cells and using them for research without her consent was not a crime. In modern ethical implication, clinical trials conducted on humans need to be accepted and confirmed participation by the participants through a procedure known as informed consent (Manti & Licari 2018). Today there are other immortal cell lines, but there still hasn’t been another cell line like HeLa, which grows in a very unique way. The contribution of these cells is going to get greater, not less. Instead of saying it should not have happened, we just need to look at how it can happen in a suitable way. Researchers have a responsibility to be sure that patients and their families understand how genetic information is used and offer their consent to allow further research on tissues and specimens so that another story similar to Henrietta Lacks’s will never happen again.
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