HeLa
HeLa is an immortalized cell line used in scientific research. It is the oldest human cell line and one of the most commonly used. HeLa cells are durable and prolific, allowing for extensive applications in scientific study. The line is derived from cervical cancer cells taken on February 8, 1951, from Henrietta Lacks, a 31-year-old African American woman, after whom the line is named. Lacks died of cancer on October 4, 1951.
The cells from Lacks's cancerous cervical tumor were taken without her knowledge, which was common practice in the United States at the time. Cell biologist George Otto Gey found that they could be kept alive, and developed a cell line. Previously, cells cultured from other human cells would survive for only a few days, but cells from Lacks's tumor behaved differently.
History
Origin
In 1951, Henrietta Lacks was admitted to the Johns Hopkins Hospital with symptoms of irregular vaginal bleeding; she was subsequently treated for cervical cancer. Her first treatment was performed by Lawrence Wharton Jr., who at that time collected tissue samples from her cervix without her consent. Her cervical biopsy supplied samples of tissue for clinical evaluation and research by George Otto Gey, head of the Tissue Culture Laboratory. Gey's lab assistant Mary Kubicek used the roller-tube technique to culture the cells. It was observed that the cells grew robustly, doubling every 20–24 hours, unlike previous specimens, which died out.The cells were propagated by Gey shortly before Lacks died of her cancer in 1951. This was the first human cell line to prove successful in vitro, which was a scientific achievement with profound future benefit to medical research. Gey freely donated these cells, along with the tools and processes that his lab developed, to any scientist requesting them, simply for the benefit of science. Neither Lacks nor her family gave permission to harvest the cells. The cells were later commercialized, although never patented in their original form. There was no requirement at that time to inform patients or their relatives about such matters, because discarded material or material obtained during surgery, diagnosis, or therapy was considered the property of the physician or the medical institution.
As was customary for Gey's lab assistant, the culture was named after the first two letters of Henrietta Lacks' first and last names, He + La. Before a 1973 query printed in the journal Nature obtained her real name, the "HeLa" cell line was incorrectly attributed to a "Helen Lane" or "Helen Larson". The origin of this obfuscation is unclear.
In 1973, staff at Johns Hopkins discovered that HeLa cells could travel through the air and easily contaminate other cell cultures. When staff at Johns Hopkins realized this, a staff physician contacted the Lacks family and sought DNA samples to help identify which non-HeLa cultures were contaminated with HeLa cells. The family never understood the purpose of the visit, but they were distressed by their understanding of what the researchers told them. These cells are treated as cancer cells, as they are descended from a biopsy taken from a visible lesion on the cervix as part of Lacks's diagnosis of cancer.
HeLa cells, like other cell lines, are termed "immortal" because they can divide an unlimited number of times in a laboratory cell culture plate, as long as fundamental cell survival conditions are met. There are many strains of HeLa cells, because they mutate during division in cell cultures, but all HeLa cells are descended from the same tumor cells removed from Lacks. The total number of HeLa cells that have been propagated in cell culture far exceeds the total number of cells that were in Henrietta Lacks's body.
Controversy
Lacks's case is one of many examples of the lack of informed consent in 20th-century medicine. Communication between tissue donors and doctors was virtually nonexistentcells were taken without patient consent, and patients were not told what the cells would be used for. Johns Hopkins Hospital, where Lacks received treatment and had her tissue harvested, was the only hospital in the Baltimore area where African American patients could receive free care. The patients who received free care from this segregated sect of the hospital often became research subjects without their knowledge. Lacks' family also had no access to her patient files and had no say in who received HeLa cells or what they would be used for. Additionally, as HeLa cells were popularized and used more frequently throughout the scientific community, Lacks' relatives received no financial benefit and continued to live with limited access to healthcare.This issue of who owns tissue samples taken for research was brought up in the Supreme Court of California case of Moore v. Regents of the University of California in 1990. The court ruled that a person's discarded tissue and cells are not his or her property and can be commercialized.
Lacks's case influenced the establishment of the Common Rule in 1991. The Common Rule enforces informed consent by ensuring that doctors inform patients if they plan to use any details of the patient's case in research and give them the choice of disclosing the details or not. Tissues connected to their donors' names are also strictly regulated under this rule, and samples are no longer named using donors' initials, but rather by code numbers. To further resolve the issue of patient privacy, Johns Hopkins established a joint committee with the NIH and several of Lacks's family members to determine who receives access to Henrietta Lacks's genome.
In 2021, Henrietta Lacks's estate sued to get past and future payments for the alleged unauthorized and widely known sale of HeLa cells by Thermo Fisher Scientific. Lacks's family hired an attorney to seek compensation from upwards of 100 pharmaceutical companies that have used and profited from HeLa cells. Settlement of the suit with Thermo Fisher Scientific was announced in August 2023, with undisclosed terms. Subsequently the Lacks family announced that it will be suing the company Ultragenyx next.
Use in research
HeLa cells were the first human cells to be successfully cloned in 1953, by Theodore Puck and Philip I. Marcus at the University of Colorado, Denver. Since then, HeLa cells have "continually been used for research into cancer, AIDS, the effects of radiation and toxic substances, gene mapping, and countless other scientific pursuits." According to author Rebecca Skloot, by 2009, "more than 60,000 scientific articles had been published about research done on HeLa , and that number was increasing steadily at a rate of more than 300 papers each month."Polio eradication
HeLa cells were used by Jonas Salk to test the first polio vaccine in the 1950s. They were observed to be easily infected by the poliomyelitis virus, causing infected cells to die. This made HeLa cells highly desirable for polio vaccine testing, since results could be easily obtained. A large volume of HeLa cells were needed for the testing of Salk's polio vaccine, prompting the National Foundation for Infantile Paralysis to find a facility capable of mass-producing HeLa cells. In the spring of 1953, a cell culture factory was established at Tuskegee University to supply Salk and other labs with HeLa cells. Less than a year later, Salk's vaccine was ready for human trials.Virology
HeLa cells have been used in testing how parvovirus infects cells of humans, dogs, and cats. These cells have also been used to study viruses such as the oropouche virus. OROV causes disruption of cells in culture; the cells start to degenerate shortly after they are infected, causing viral induction of apoptosis. HeLa cells have been used to study expression of the papillomavirus E2 and apoptosis. HeLa cells have also been used to study the ability of the canine distemper virus to induce apoptosis in cancer cell lines, which could play an important role in developing treatments for tumor cells resistant to radiation and chemotherapy.HeLa cells have also been instrumental in the development of human papilloma virus vaccines. In the 1980s, Harald zur Hausen found that Lacks's cells from the original biopsy contained HPV-18, which was later found to be the cause of the aggressive cancer that had killed her. His work in linking HPV with cervical cancer won him a Nobel Prize and led to the development of HPV vaccines, which are predicted to reduce the number of deaths from cervical cancer by 70%.
Over the years, HeLa cells have been infected with various types of viruses, including HIV, Zika, mumps, and herpes viruses to test and develop new vaccines and drugs. Dr. Richard Axel discovered that the addition of the CD4 protein to HeLa cells enabled them to be infected with HIV, allowing the virus to be studied. In 1979, scientists learned that the measles virus constantly mutates when it infects HeLa cells, and in 2019 they found that Zika cannot multiply in HeLa cells.
Cancer
HeLa cells have been used in a number of cancer studies, including those involving sex steroid hormones, such as estradiol and other estrogens, and estrogen receptors, along with estrogen-like compounds, such as quercetin, which has cancer-reducing properties. There have also been studies on HeLa cells, involving the effects of flavonoids and antioxidants with estradiol on cancer cell proliferation.In 2011, HeLa cells were used in tests of novel heptamethine dyes IR-808 and other analogues, which are currently being explored for their unique uses in medical diagnostics, the individualized treatment of cancer patients with the aid of PDT, co-administration with other drugs, and irradiation. HeLa cells have been used in research involving fullerenes to induce apoptosis as a part of photodynamic therapy, as well as in in vitro cancer research using cell lines. HeLa cells have also been used to define cancer markers in RNA, and have been used to establish an RNAi Based Identification System and Interference of Specific Cancer Cells.
In 2014, HeLa cells were shown to provide a viable cell line for tumor xenografts in C57BL/6 nude mice, and were subsequently used to examine the in vivo effects of fluoxetine and cisplatin on cervical cancer.