WEDNESDAY, 13 DECEMBER 2023THE HISTORY OF THE HELA CELL LINE
In 1951 at Johns Hopkins Hospital in Maryland, USA, a 31-year-old African American woman named Henrietta Lacks was diagnosed and treated for cervical adenocarcinoma. In the first half of the 20th century, cervical cancer was the fourth deadliest type of cancer in women, accounting for almost 14% of female cancer deaths in the USA. Dr George Otto Gey, a cell biologist from Johns Hopkins Hospital, started growing cells from her cervical tumour in a laboratory mere months before Lacks passed away, leaving behind five children. He named the isolated cells HeLa after Henrietta Lacks.
THE UNIQUE PROPERTIES OF HELA CELLS
Replicability is the foundation of scientific studies as it enables verification. The use of HeLa cells in biomedical research allowed researchers to replicate experiments using genetically identical cells anywhere, anytime. This eliminates potential unknown effects arising from genetic differences. HeLa cells are an immortalised cell line: a cell population isolated from a multicellular organism that can divide indefinitely in laboratory environments outside of the organism. Normally, animal cells can only grow in their native environments, with appropriate intercellular contacts and signalling from neighbouring cells, orchestrated by self-regulating networks as part of a whole organism. Such mechanisms eliminate mutated cells to prevent them from uncontrollably proliferating and causing cancer in animals. Typically, the number of divisions from a cell is also limited by a consumable resource — telomeres, which gradually deplete and lead to cell death. Telomeres are repetitive DNA sequences protecting the structural integrity of the ends of the chromosomes, which shorten with every cell cycle. However, a series of mutations enabled HeLa cells to evade these regulations and grow independently from a human body for prolonged periods while constantly regenerating telomeres. In fact, this inspired the modern approach to creating immortal cell lines from any isolated cells by telomere regeneration.
Fun fact: Evolutionary biologist Leigh Van Valen proposed in his article “HeLa, a New Microbial Species” to classify HeLa cells as a new organism because of their non-human chromosome number and their ability to replicate without a host.
HOW HELA CELLS SHAPED SCIENCE
HeLa is the oldest immortal cell line and is widely used in cancer, virology, and genetics research. The cell line was used in developing the polio vaccine and COVID-19 vaccine, as well as in the study of mumps, measles, Ebola, and HIV. HeLa cells were the first human cells to be cloned and were even sent to space to explore the effects of radiation on astronauts. More than 110,000 scientific studies using HeLa cells have been published, with a yearly increase of over 6,000 new articles in 2015 and 2016, according to data compiled by the National Institutes of Health.
The HeLa cell line was essential in the studies linking cervical cancer to human papillomavirus (HPV) infection, leading to Herald zur Hausen winning the Nobel Prize in Physiology or Medicine in 2008. He was one of the first to link certain types of human cancer to viral infections. This discovery paved the way to the development of the HPV vaccine Gardasil, which was FDA approved in 2006. This was followed by Ceravix and Gardasil 9, which have since decreased the cervical cancer incidence by almost 90% in women vaccinated under the age of 13, according to a study funded by Cancer Research UK. However, the characteristics of HeLa cells are not always helpful to science. The accumulation of genetic mutations means that HeLa cells are very different from normal human cells. For example, their genetic material comprises over 80 abnormally structured chromosomes, instead of the standard 46. Thus, inferring knowledge about the human body using findings from HeLa cell experiments can be controversial. Additionally, the contamination of other cell culture experiments by HeLa cells is very common, because of their ubiquitous and highly proliferative nature. According to a report by Science (2015), over 7,000 peer-reviewed publications had unknowingly used other human cells contaminated by HeLa.
Not-so-fun fact: The contamination of other samples by HeLa cells contributed to increased tensions between the USA and the USSR during the Cold War, as the USSR scientists thought that internationally exchanged samples were deliberately contaminated.
HOW HELA SHAPED SOCIETY
HeLa cells helped make important advances in biomedical research, leading to tremendous societal benefits. For example, with the development of the Gardasil vaccine in combination with regular cervical screenings, the World Health Organisation (WHO) set a goal towards the elimination of cervical cancer. Canfell et al. predicted that the triple-intervention strategy by the WHO, including upscaling cervical cancer treatment, vaccination, and screening, will reduce the mortality of the disease by 99% by 2120.
However, the story of Henrietta Lacks has sparked controversy in recent years, as new discussions have been opened about ethics in scientific research. We can only speculate if Lacks’ sex and race were reasons for her exploitation. Although it was not common courtesy to ask any patients for consent when extracting samples in the early 20th century, African American individuals were exploited especially brutally for scientific research. From the 1930s to the 1970s, the Tuskegee Syphilis Study was carried out on over 400 African American men with syphilis, intentionally leaving them untreated for the disease to study its effects, leading to over 100 deaths.
Equally controversial is the ongoing lawsuit the Lacks family filed against Thermo Fisher in October 2021, one of the most prominent and rapidly growing biotechnology companies with an annual revenue of $44 billion in 2022. The Lacks family are seeking compensation in royalties from the company for profiting off commercialising HeLa cells decades after the consent issue had been raised. While there is widespread support for the Lacks family, others dismiss the claims on the grounds that the time limit for initiating legal proceedings has passed. Despite the controversy, the Lacks family are still fighting for more ethical medical research.
ETHICS OF USING HUMAN SAMPLES IN SCIENTIFIC RESEARCH
In the USA, human research subjects are under the protection of the Common Rule, adopted in 1991, which states that voluntary, informed consent and protection of vulnerable groups is essential for ethical research. Under today's jurisdiction, Lacks would be protected as a member of a vulnerable group and research using her cells would only be done with her consent. This law does not, however, confer protection retrospectively. HeLa cells have been excluded from the definition of a human subject after the passing of Lacks.
My work as an HPV researcher involves handling human samples and practising the relevant ethical code. In England, Wales, and Northern Ireland, all research involving the use, removal, storage, or disposal of human bodies, organs, and tissue, must follow the regulations of the Human Tissue Act 2004. Human cells and anything containing genetic material is classified as ‘Relevant Material’. Legal and ethical complications arise as many research samples are collected in other jurisdictions. For instance, my research uses human samples collected in South Africa, but analysed in the UK. As the two countries have different ethical codes and legal regulations surrounding human sample collection and handling, does this work remain ethical as long as the procedures conducted in each jurisdiction follows local ethical codes, even if they violate the code of another participating jurisdiction? While there are regulations in place for international collaborations, the processes can be long and poorly understood. Do legal regulations equate to ethics? To extend this to a broader level, does societal benefit ever outweigh the personal welfare of vulnerable patients, and is it even valid to weigh objective benefits to the society with the subjective human experience? Such contemplations may never have definite answers but are worth pondering for both the researcher and the everyday person who benefits from debatable research practices.
Lacks’ family wanted her legacy to live on, with a focus on the societal progress that arose from the creation of the HeLa cell line. Her legacy lives on through articles, statues, and even New York Times bestselling books. We should thank her, unfortunately only posthumously, for shaping the scientific and ethical progress of modern medical research.
Konstanze Schichl is a 1st year PhD student studying human papillomavirus and cervical cancer at Peterhouse, University of Cambridge. Konstanze is particularly interested in the gender equality in research. Illustration by Caroline Walker.