Genomic Research Ethics: Special Rules for HeLa Cells

In her 2010 book The Immortal Life of Henrietta Lacks, Rebecca Skloot told the story of Henrietta Lacks and the cell lines derived from her cervical tumor biospecimen (cell lines known to scientists simply as “HeLa cells”). To make a long story short, in 1951 physicians at Johns Hopkins Hospital took a biopsy from a patient, Henrietta Lacks, and from that biospecimen developed the first human cancer cell line. The biospecimen was taken without Lacks’ knowledge or informed consent. No laws were broken in the creation of the HeLa cell lines that are now recognized (pdf) as “the most widely used human cell line in the world.” She died in 1951, and it was reportedly not until 1973 that her family learned about the HeLa cells (two years after Henrietta Lacks’ name was published as the source of HeLa cells in a scientific journal). As the table below shows, this incident occurred long before the adoption of regulations and ethical guidelines for biomedical research that, today, generally require researchers to obtain voluntary, informed consent from individuals before performing biomedical experiments.

Significant Developments in Ethical and Legal Governance of Biomedical Research

Year Policy Policy Summary Source of Policy
1947 Nuremburg Code (pdf) Advocates for informed consent and voluntary participation in medical research United States v. Brandt (Nuremberg Military Tribunal)
1948 Universal Declaration of Human Rights Includes Art. 27 (1): “Everyone has the right freely to participate in the cultural life of the community, to enjoy the arts and to share in scientific advancement and its benefits.” United Nations
1964 Declaration of Helsinki Issues ethical principles for medical research World Medical Association
1974 National Research Act (pdf),
Pub. L. 93-348
Creates the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research and requiring creation of Institutional Review Boards (IRBs) to review study protocols – Prompted by publicity of the Tuskegee Syphilis Study U.S. Congress
1979 Belmont Report Articulates ethical principles of (1) respect for persons, (2) beneficence, and (3) justice for research involving human subjects National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research
1991 The Common Rule,
45 CFR 46 subpart A
Establishes basic protections for human subjects in research conducted by or supported by the DHHS Department of Health and Human Services and other federal agencies and departments
2011 “Human Subjects Research Protections: Enhancing Protections for Research Subjects and Reducing Burden, Delay, and Ambiguity for Investigators” Advance Notice of Public Rulemaking (ANPRM) (pdf), 76 FR 44512 Proposes policy changes to the basic protections for research involving human subjects/participants Department of Health and Human Services

Recent HeLa Genome Sequencing Efforts and Bioethical Controversy

In March 2013, scientists from European Molecular Biology Laboratory in Heidelberg, Germany, published the genomic sequencing of a HeLa cell line and deposited that genomic sequence data in an online, open-access database (JJ Landry et al. 2013). At that time, a separate, more detailed sequencing effort of a second HeLa cell line was in preparation for publication by scientists from the University of Washington in Seattle, WA (Adey et al. 2013). The family of Henrietta Lacks had not been consulted or notified prior to the publication of the HeLa cell line sequence. While there was no law requiring such action, the circumstances surrounding the Henrietta Lacks story led many bioethicists to question why the family was left in the dark yet again.

The initial reaction to the publication of the HeLa cell line sequence data prompted the researchers to remove the data from the online databases. While some scholars wondered how this drastic action could be warranted given the vast amounts of genomic data for HeLa cell lines already published, other scholars questioned how the peer-review process failed to consider the interests of the family of Henrietta Lacks.  Skloot herself responded critically to the publication in an op-ed piece published in the New York Times as “The Immortal Life of Henrietta Lacks: the Sequel.” There, Skloot underscored that privacy concerns by and respect for members of the Lacks family are at the heart of the controversy. And while she acknowledged that consent had not been required, Skloot condemned the “whole system” of biomedical research for failing to raise questions about consent during the peer-review process.

For further reading on the March incident and discussion:

Special Rules for HeLa Genomic Research

Over the following four months (April to July 2013), engagement with family members of Henrietta Lacks by the National Institutes of Health (NIH) – along with the assistance of Rebecca Skloot – culminated in a consent agreement setting forth how genome sequence data from HeLa cell lines can be published and shared for additional research. The agreement requires (1) any publication of HeLa sequence data to be placed in a controlled-access database (known as dbGaP, the Database of Genotypes And Phenotypes), (2) the creation of a HeLa Genome Data Access Working Group that will process applications for access to the data and on which the Henrietta Lacks family members will have representation, and (3) a request that any research study provide acknowledgement to Henrietta Lacks and her family for their generous contributions to the biomedical community. The agreement does not involve any compensation or rights to benefit from products and discoveries generated with or derived from the HeLa cell lines or genomic data. These rules – involvement of family members to determine, on a case-by-case basis, whether access to HeLa genomic data should be granted and a mandate regarding where data can be deposited – are described by the NIH Director and NIH Deputy Director for Science, Outreach, and Policy as “not setting a precedent for research with previously stored, de-identified specimens.” The factors identified by Hudson and Collins as setting the Lacks case apart and justifying the special rules for HeLa genome research are (1) the collection of the biospecimens without consent for collection and use, (2) the pervasive usage of the resulting cell lines in biomedical research, and (3) the extent to which the family members of the biospecimen’s source are known by name. The researchers who sequenced two HeLa cell lines have cooperated with the consent agreement described above.

For further reading on the August updates:

Beyond Henrietta Lacks and HeLa Cell Lines

There are many challenging ethical and legal issues raised by the Henrietta Lacks case:

  • What is “informed consent”? Who can provide it?
  • Can open or blanket consent be effective?
  • Is “informed consent” a one-and-done transaction or an iterative process?
  • What ongoing duties do researchers have to those individuals who contributed biospecimens to research prior to current guidelines?
  • Who owns our biospecimens? Who owns our genome? Who owns commercial products derived from our biomedical research contributions?
  • What privacy interests does an individual have in his/her genome, biospecimens, medical information, personal information, and other data? How are those privacy interests protected? Do these privacy rights or protections extend to family members?
  • Who can dictate the terms for biomedical research? To what extent do family members get a say in an individual’s participation in biomedical research? Can family members, heirs, executors, administrators, and the like withdraw an individual’s data from biomedical studies?
  • What is “de-identification” of data? Are genomes ever de-identified? What are individual risks of re-identification?
  • How can archived samples be studied ethically? How can research be conducted ethically using specimens of deceased individuals?
  • Can surreptitious research of biospecimens ever be considered ethical?

These topics — informed consent, open access for genomic research, property rights in genetic material and data, gene patents, familial searching, and surreptitious testing — are familiar and frequent topics in the Genomics Law Report. While the Lacks case is the focus of much attention these days, the challenges of informed consent were also brought to the forefront not too long ago in the controversial research involving the Havasupai Indians. In 2010 the Havasupai, challenging the adequacy of the informed consent when biospecimens were believed to have been collected only for diabetes research but were later discovered to have been used in research for other purposes, successfully limited genomic research using their samples and settled litigation against the researchers at Arizona State University. Another example of the bioethical challenges with research involving samples collected prior to modern bioethical research principles is the persistent controversy surrounding Yanomami studies by James Neel and Napoleon Chagnon in the 1960s and 1970s. (For further reading on the Yanomami controversy, see “Sociobalderdash and the Yanomami?” Part I and Part II at The Mermaid’s Tale). Even the Personal Genome Project — with an intricate informed consent process (including an entrance exam), participant control of their profile information, and participant assumption of risk associated with the placement of their genomic data into the public domain — has had its own brush with controversy, as differing expectations popped up regarding demonstrations of participant’s risk of re-identification.

While policymakers debate potential reforms to provide better protection for research participants in this global, mobile, genomic, informational age, there are no easy answers. Context has always been key, and what is “reasonable” is an evolving standard. It is also important to avoid falling into the trap of the historian’s fallacy. Practices considered appropriate and acceptable for biomedical research decades ago may be considered wholly unacceptable today. Using one family’s experience as a case study to advocate for policy reform can be persuasive and effective. But there is a point at which the advocacy itself becomes exploitative and even counter-productive. Has Skloot (any of the bioethicists, journalists, or others for that matter) crossed that line by continuing to draw attention to the Lacks family? Declaring HeLa cells as her “legacy” or the Lacks family legacy (as has been done in reporting the agreement reached for HeLa genomic research to continue with Lacks family support) does not demonstrate that the important lessons of the Henrietta Lacks case have been learned. Indeed, it seems quite presumptuous of us all to declare what someone else’s (or indeed what an entire family’s) legacy is – a point more fully articulated by Ken Weiss at The Mermaid’s Tale. To learn the lesson requires all of us to engage in active and proactive policymaking rather than reactive cries for policy reform. Personally, I am tired of the lack of political will to do anything on any issue unless we have a tragedy with which to force the reforms through. That type of policymaking is bad for all of us.

We must consider the diverse perspectives, needs, and interests of the individuals making generous contributions to science. At the same time, we must determine the boundaries of their say regarding what happens with those contributions (whether biospecimens or data), both now and in the future. We need to throw away the “one-size-fits-none” approach to the protection of research participants. Transforming the biomedical research enterprise into a participatory process is one step in the right direction, but it is not possible for all situations (unless research with archived samples were to cease). There is no one (singular) ethical “right way” to conduct scientific research. Ethical issues are not just implications, complications, or after-the-fact consequences of genomic research. The ethical dimensions must be integrated within research design and practice in order, quite simply, to do better science.