# Professionalism/HeLa Cells and Timeless Ethics

Since 1951, the use of HeLa cells has been mired in ethical questions regarding patient consent, use of biological materials, and public access to genomic data. This chapter briefly details the history of HeLa cells and explores how the cells have advanced medical treatment and shaped biomedical policy.

## Henrietta Lacks & the Origin of the HeLa Cell Line
##### Cell Removal

Henrietta Lacks, a poor black woman, was born in rural Virginia on August 1, 1920. On January 29, 1951, Henrietta sought treatment at Johns Hopkins Hospital for pain that was later diagnosed as cervical cancer. When Henrietta came to Hopkins, Dr. George Otto Gey was studying malignant tumor cells, trying to culture them outside the body and use them to cure cancer. Henrietta's doctor, Richard Wesley TeLinde, removed some of her cancerous cells during a biopsy and gave them to Gey for his research, without Henrietta's consent or knowledge. Henrietta's cells grew exponentially when Gey cultured them, becoming the first "immortal" cell line, which he named "HeLa" for the first two letters of Henrietta Lacks's names. At the time, no law or code of ethics required doctors to ask permission before taking tissue from a living patient.
When Henrietta passed away on October 4, 1951, Gey had already begun using HeLa cells for his studies and distributing them to colleagues, but the Lacks family remained uninformed. So he could get more cells from different tumors, Gey asked for permission from Henrietta's husband, David Lacks, to perform an autopsy and he initially refused. He later agreed, but it is unclear if he agreed to just the autopsy or also the tissue removal. If he was informed about the tissue removal, David was not informed about how the cells could be used.

##### Use in Research

As Gey began culturing HeLa cells in large quantities, he developed a better method for cell culturing and shipment. He also used HeLa cells to help stop polio. The early 1950s was the biggest polio epidemic in history and to test Jonas Salk's recently developed vaccine, scientists needed cheap cells. The Tuskegee Institute was selected as the location for a HeLa cell factory, headed by Charles Bynum, a black science teacher and civil rights activist. The partnership with Tuskegee not only produced enough cells to effectively test the polio vaccine, but also provided "hundreds of thousands of dollars in funding, many jobs, and training opportunities for young black scientists and reduced the need for animal test subjects." Following the development of the vaccine and a mass immunization campaign, the annual number of polio cases in the U.S. fell from 35,000 in 1953 to just 161 cases in 1961.
Recognizing the power of these cells for research, Gey gave them away for free to researchers around the world. HeLa cells have informed research about cancer, herpes, leukemia, HIV/AIDS, influenza, Parkinson's disease, hemophilia, in vitro fertilization, the effects of radiation, and more. One biographical archive says that Henrietta, "has had a greater impact on science than any other scientist or researcher will ever claim, and her cells have been used to save the lives of a countless number of people and animals."

##### Confidentiality

The first report linking the woman behind the cells to the cells themselves was published in November, 1953, by the Minneapolis Star. The article misreported Henrietta's identity as "a Baltimore woman named Henrietta Lakes," and no one knows who leaked the information to the press. When more people started to investigate the case, George Gey and Richard TeLinde agreed to allow the story to run in a popular magazine, but insisted repeatedly on withholding Henrietta's name. Another story ran later, naming HeLa cells after a woman named "Helen Lane," which may have been accidental misinformation or may have been a deliberate pseudonym Gey used to "throw journalists off the trail of Henrietta's real identity." The slew of mis-naming that followed these articles prevented Henrietta from getting recognition, prevented her family from finding out about how her cells had been used, and temporarily prevented the family's medical information from becoming public information. Somehow, a book was published in 1986, citing detailed information from Henrietta's medical records. Again, no one knows who gave the writer the medical records.
Patient confidentiality is a key component of the doctor-patient relationship. The Hippocratic Oath states that, "I will respect the privacy of my patients, for their problems are not disclosed to me that the world may know." The Health Insurance Portability and Accountability Act of 1996 (HIPAA) formalized some confidentiality measures, but at the time of Henrietta's case, there was no such law. George Gey and Richard TeLinde worked to protect Henrietta's privacy and confidentiality, though information still managed to get out. Publishing Henrietta's medical records was not strictly forbidden at the time, if the journalist received them from a medical professional, but doing so without the family's consent may have been questionable given the expectations at the time.

## Profitability of Biological Materials

The HeLa cell line has enabled a massive industry that profits from selling cells or cell-derived products. It has also spurred innumerable related industries that specialize in products derived from discoveries made using the HeLa cell line. However, the Lacks family was oblivious of these financial profits and since learning the full extent to which HeLa cells have been commercially utilized, comment on the unfairness: "I don't know if they didn't give us information because they was making money out of it, or if they was just wanting to keep us in the dark about it...Hopkins says they gave them cells away...but they made millions! It's not fair! She's the most important person in the world and her family living in poverty." The question of whether Lacks family should have financially profited from HeLa cell-derived products closely mirrors those in the cases of John Moore and Ted Slavin.

##### John Moore

John Moore was a patient diagnosed with hairy cell leukemia in 1976. His physician, Dr. David Golde, realized the financial potential of products derived from Moore's tissue and prompted him to sign consent forms releasing the rights to his genetic materials. Over a span of seven years, Moore became increasingly more wary of Golde's intentions and eventually learned that Golde had patented an in vitro cell line from his biological materials. In a landmark case, the Supreme Court of California ruled that Moore had no right to any share of profits derived from his biological products since he had chosen to discard them.

##### Ted Slavin

Ted Slavin was born a hemophiliac. Since his body could not produce the necessary clotting factors, Slavin underwent many blood transfusions throughout his lifetime, was exposed to the hepatitis B virus through these transfusions, and thus carried a high concentration of hepatitis B antibodies in his blood. Slavin's physician informed him that researchers working to produce a hepatitis B vaccine would pay for his serum. Empowered by this information, Slavin was able to sell his serum to pharmaceutical companies and partner with Nobel Prize virologist Baruch Bloomberg to develop the first hepatitis B vaccine.

##### Use of Privileged Information

Slavin's ability to profit from his biological materials as well as Moore and Lacks's inability to do the same is critically linked to the information provided by their physicians. Although no law requires physicians to disclose this information, it is important to consider whether it is their ethical obligation to do so. The boundary between research and commercialization is often blurred and biological samples, once collected, are often repurposed. Physicians with access to biological wastes and knowledge of their commercialization potential are uniquely positioned to exploit their knowledge if not governed by an ethical code that prevents them from doing so.

## Influence on Biomedical Policy
##### Controlled Access to the HeLa Genome

Privacy concerns about publishing the HeLa cell genome led to the creation of National Institutes of Health (NIH) policies to control access to the data. On March 11, 2013, the European Molecular Biology Laboratory (EMBL) in Heidelberg, Germany, published information about the genomic sequence of a HeLa cell line in a scientific journal without the consent of the Lacks family. The Lacks family was displeased that they had not been consulted about the article and raised privacy concerns about the genomic data being publicly available. Although the EBML withheld access to the data after the Lacks family raised their concerns, the EMBL said that “we cannot infer anything about Henrietta Lacks’s genome, or of her descendants, from the data generated in this study.” Scientists disproved this by uploading the HeLa genome to a public website called SNPedia that translates genetic information. The website was able to provide detailed personal information about the Lacks family from the data the EMBL published. Yaniv Erlich, a fellow at the Whitehead Institute of Biomedical Research, and other scientists found that anonymous donors could be identified through public online databases if their DNA was sequenced and published. Researchers are not required to inform donors that their genomic sequence is not guaranteed to remain anonymous. Although it is illegal for health insurance companies and employers to discriminate based on genetics under the Genetic Information Nondiscrimination Act (2005), there are no such laws for long-term care, and life and disability insurance providers.
Although there was relatively little outrage over the EMBL publication, after it was published, Francis Collins, director of the NIH, learned that a more detailed genomic study on HeLa cells funded by the NIH was accepted for publication in Nature, a high profile scientific journal, and intervened. The article was withheld from publication while Collins, his chief adviser, two mediators from Johns Hopkins University, and Skloot met three times with the children and grandchildren of Henrietta Lacks at Johns Hopkins to discuss the publication and use of the HeLa genome. On August 7, 2013, the family allowed for the EMBL and Nature publications to be released and the creation of a restricted-access database containing data on the full genome sequence of HeLa cells. An NIH working group of six committee members, including two Lacks family members, was formed to review applications for access to the database. Researchers that are granted access are required to use the data for research only, and are expected to submit their findings to the database and acknowledge the Lacks family's contributions in any publications and presentations.

##### Acknowledging the Contribution of the Lacks Family to Society

The Lacks family was acknowledged for their contributions to biomedical research during the discussions with Collins. During the meetings at Johns Hopkins, Collins took the time to explain the usage of HeLa cells, genomic sequencing, and the implications of publishing the genome. “It was the first time in the very long history of HeLa cells that any scientists have sat down and devoted complete attention to explaining to the family what was going on,” said Skloot. The NIH arranged for clinical genetic experts to explain what information could be revealed about the family in the HeLa genome and offered to have family member's genomes sequenced and interpreted. Collins said that “philanthropy is the altruistic donation of precious resources for the benefit of others. We should all count Henrietta Lacks and her family among the greatest philanthropists of our time.” For those that are granted access to the HeLa cell genome database, the NIH encourages researchers to acknowledge Henrietta Lacks and her family by including the following on all publications and presentations: “The genome sequence described/used in this research was derived from a HeLa cell line. Henrietta Lacks, and the HeLa cell line that was established from her tumor cells without her knowledge or consent in 1951, have made significant contributions to scientific progress and advances in human health. We are grateful to Henrietta Lacks, now deceased, and to her surviving family members for their contributions to biomedical research. This study was reviewed by the NIH HeLa Genome Data Access Working Group."

##### Consent and Legislation Changes

Policy and legislation changes aim to increase the protection of patients' rights and privacy. Researchers with firsthand contact with patients are required to obtain patient consent to conduct research on the patient's discarded tissue. In 2013, the US Supreme Court ruled that unmodified genes could not be patented.

## Key Ethical Questions

The HeLa case study yields interesting ethical questions. Specifically:
* Was removing Henrietta's cells ethical?
* Was it ethical for Henrietta's medical records or her name to be released?
* Should physicians inform their patients of the potential commercial value of their biological materials?
* Should concern be raised over the publication of an identified persons genome?
* Can the HeLa case be applied to other cases or is it unique, as Francis Collins suggests?
Generalizing these questions, this case provides fodder for general debate about:
* Do decisions made in the present only contend with modern understanding of ethics? Should past decisions be held to today's ethical standards?
* Do ethics change over time?

## Future Works

With additional information, these may be interesting new questions to consider:
* What guidelines should physicians follow for reporting profitability of patient's biological materials?
* How much did George Gey profit from HeLa cells? How does this affect the answer to the question, "Was it ethical to remove Henrietta's cells?"
* Does Hopkins being a free hospital matter? How so?
* Did Henrietta's physicians have a responsibility to tell her family about how rare and aggressive her cancer was?
* Should physicians have been required to explain what "cells," "autopsy," etc. were to the Lacks family?
* Should the Lacks family profit from the publication of Rebecca Skloot's book? The forthcoming movie?

## References

* 1 2 3 4 5 6 7 8 9 Skloot, R. (2010). The immortal life of Henrietta Lacks. New York, NY: Crown.
* ↑ Special to the New York Times. (1955, January 5). Unit at Tuskegee helps polio fight: Corps of negro scientists has key role in evaluating of Dr. Salk's vaccine. New York Times.
* ↑ Ross, G. (2016). 62 years ago: First mass trials of the Salk polio vaccine. American Council on Science and Health. http://acsh.org/
* ↑ Miyagawa, S. (2014). Henrietta Lacks (1920-1951). MSA SC 3520-16887. Maryland State Archives Biographical Series.
* ↑ Gold, M. (1986). A conspiracy of cells: One woman's immortal legacy and the medical scandal it caused. New York, NY: State University of New York Press.
* ↑ Lasagna, L. (1964). The Hippocratic Oath. Johns Hopkins. http://guides.library.jhu.edu/
* ↑ Petrini, C. (2012). Ethical and legal considerations regarding the ownership and commercial use of human biological materials and their derivatives. Journal of Blood Medicine, 3, 87.
* ↑ Sloot, R. (2006, April 16). Taking the least of you. New York Times.
* ↑ Warwick R. M., Fehily D., Brubaker S. A., & Eastlund T. (Eds.). (2009). Tissue and cell donation: An essential guide. Hoboken, NJ: Wiley-Blackwell.
* ↑ Laundry, J. J., Pyl, P. T., Rausch, T., Zichner, T., Tekkedil, M. M., Stutz, A. M.,...Steinmetz, L. M. (2013). The genomic and transcriptomic landscape of a HeLa cell line. G3 (Bethesda), 3(8), 1213-1224.
* ↑ European Molecular Biology Laboratory (2013). HeLa genome online. https://www.embl.de
* 1 2 3 Skloot, R. (2013). The immortal life of Henrietta Lacks, the sequel. The New York Times. http://www.nytimes.com
* ↑ National Human Research Institute (2012). Genetic discrimination in health insurance or employment. https://www.genome.gov
* 1 2 3 Callaway, E. (2013). Deal done over HeLa cell line. Nature, 500(7461).
* ↑ Adey, A., Burton, J. N., Kitzman, J. O., Hiatt, J. B., Lewis, A. P., Martin, B. K.,...Shendure, J. (2013). The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer line. Nature, 500(7461), 207-211.
* ↑ National Institutes of Health (2013). NIH, Lacks family reach understanding to share genomic data of HeLa cells. https://www.nih.gov
* ↑ McManus, R. (2013). NIH restricts access to Henrietta Lacks' genomic data. NIH Record. https://nihrecord.nih.gov.
* ↑ National Institutes of Health (2013). Notice of NIH acknowledgement and use of HeLa cell whole genome sequence data. https://grants.nih.gov
* ↑ Department of Health and Human Services (2009). Code of federal regulations part 46. http://www.hhs.gov
* ↑ Supreme Court of the United States (2013). Association for Molecular Pathology et al. v. Myriad Genetics Inc., et al. http://www.supremecourt.gov
* ↑ Callaway, E. (2013). NIH director explains HeLa agreement. Nature.