The Henrietta Compromise: NIH Announces HeLa Data Use Agreement

August 7, 2013

By Allison Proffitt 
August 7, 2013 | The National Institutes of Health announced this morning that it has reached an “understanding” with the family of Henrietta Lacks to allow controlled access to whole genome sequence data from HeLa cells, the cells derived without consent from the tumor of Henrietta Lacks in 1951.  
The HeLa Genome Use Data Agreement establishes a six-person panel—including two representatives from the Lacks family—to review applications for access to the HeLa genome and set parameters for its use.
During a press briefing this morning, NIH Director Francis Collins, NIH Deputy Director for Science, Outreach, and Policy Kathy Hudson, and three members of the Lacks family presented the Agreement and discussed the circumstances that precipitated it. 
"NIH is grateful to this remarkable family for their willingness to collaborate with us on this very important issue," Collins said during the press conference. "It's fitting--given the priceless contributions Henrietta Lacks's family has made to science and medicine--that her story is now catalyzing changes in policy. We should all count Henrietta Lacks and her family as among the greatest philanthropists of our time when you consider how they contributed to the advancement of science and our health." 
Under the terms of the HeLa Genome Use Data Agreement, biomedical researchers who agree to abide by the terms of the agreement will be able to apply to NIH for access to the full genome sequence data from HeLa cells. Along with representatives from the medical, scientific, and bioethics communities, two representatives of the Lacks family--David Lacks Jr., Henrietta's grandson and Veronica Spencer, Henrietta's great granddaughter--will serve on NIH’s newly formed, six-member working group that will review proposals for access to the HeLa full genome sequence data.
NIH-funded researchers who generate full genome sequence data from HeLa cells will be expected to deposit their data into the NIH HeLa dbGaP database for future sharing through this process, while other researchers are expected to respect the family’s wishes and do the same. All researchers who use or generate full genomic data from HeLa cells are formally asked to include in their publications an acknowledgement and expression of gratitude to the Lacks family for their contributions. The agreement also mandates that researchers not attempt to contact any members of the Lacks family. 
Any lab receiving NIH funding will be expected to abide by the terms of the HeLa Genome Use Data Agreement as part of their grant terms. However, NIH is "fully aware" that existing published data could be "pieced together" and that "any lab with the right equipment could derive the whole sequence at any point without NIH funds," said Hudson. But she stressed that, "Such actions would not be right and would not be respectful of the Lacks family." 
Collins and Hudson released a Nature comment this morning describing their collaboration with the family to develop the new policies and also examine some of the larger questions about protection of research participants in the expanding field of genomics research. 
Representing the Lacks family at the press conference were Jeri Lacks Whye, Henrietta Lacks's granddaughter and family spokesperson; David Lacks Jr., Henrietta's grandson; and Veronica Spencer, Henrietta's great granddaughter. 
The agreement includes no financial component for the Lacks family. David Lacks, Jr. and Veronica Spencer will be reimbursed for their time on the working group panel in accordance with the "modest" government travel, accommodation, and per diem rates that are standard for NIH, Hudson said. 
While thanking the Lacks family for their participation in the process, Francis Collins was quick to point out that HeLa cells present a unique problem and challenge in the scientific community. 
“The sequencing and posting of the HeLa genome brought into sharp relief important ethical and policy issues,” he said in the press release. “To understand the family’s perspectives, we met with them face to face three times over four months, and listened carefully to their concerns. Ultimately, we arrived at a path forward that respects their wishes and allows science to progress. We are indebted to the Lacks family for their generosity and thoughtfulness.”
But he does not expect the HeLa agreement to serve as a model for future issues. 
"This should not be seen as setting a precedent for other global cell lines," he stressed during the briefing. "In 20 years at NIH I can't recall a specific circumstance more charged  with scientific, societal, and ethical challenges than this one." 
But as the issues around DNA privacy evolve, it's unlikely that the HeLa agreement won't inform future decisions. 
"NIH considers the widespread use of Henrietta Lacks’ cells a unique circumstance and does not expect to enter into future data use agreements for other cell lines. However, it is highly unlikely that this will be an isolated event," said Claire Cowart Haltom, a health care attorney for Baker Donelson in Nashville, Tennessee. 
"As science enables us to extract more information from cells and DNA, expect stakeholders to demand data use agreements in an effort to control how that information may be used. This information may be tremendously valuable to science, but it raises significant privacy concerns for those involved.”
HeLa History
The HeLa cell line was originally derived without permission from a tumor from Henrietta Lacks, a 31-year-old African American woman who died of a particularly aggressive strain of cervical cancer at Johns Hopkins University in 1951. Lacks’ story gained international attention with the publishing of the 2010 book, The Immortal Life of Henrietta Lacks, by Rebecca Skloot.
Although HeLa cells have been used in worldwide research since their harvesting in 1951—the NIH says the cells are the most widely used human cell lines in existence today—the questions of privacy and rights that Skloot raised were redoubled earlier this year when a group of German researchers conducted whole genome sequencing on their strain of cells and published the results in Genes, Genomes, Genetics--G3. 
The published sequence drew the attention of researchers, bioethicists, and patient advocates on Twitter and blogs. Some researchers were alarmed; others said that the ubiquitous cell lines didn’t really reflect on the living members of the Lacks family.
Rebecca Skloot, who has served as a liaison with the Lacks family, weighed in on the topic in the New York Times. “The publication of the HeLa genome without consent isn’t an example of a few researchers making a mistake. The whole system allowed it. Everyone involved followed standard practices. They presented their research at conferences and in a peer-reviewed journal. No one raised questions about consent,” she said in her opinion piece.
Michael Eisen, a biologist at UC Berkeley and open science advocate, agreed that HeLa cells weren’t originally collected with informed consent and said that he believes they should not be used in research now. But he believes that the original consent is a separate issue from the family’s current stake in the sequence data.
“This has nothing to do with the history of Henrietta Lacks and HeLa cells,” Eisen says in a blog in response to Skloot’s op-ed. “It is an active assertion about familial privacy rights that would—if you accept it—be just as true if the paper in question had described the sequencing of anyone else’s genome. Why weren’t the same issues raised when the genome belonged not to Henrietta Lacks, but to Jim Watson or Craig Venter?”
Nevertheless, the German researchers, led by Lars Steinmetz, expressed surprise at the reaction and removed the sequence from public databases. “We wanted to respect the wishes of the family,” Steinmetz told Nature in March, “and we didn’t intend to cause them any anxiety by the publication of our research.” Steinmetz said he reached out to the family via Skloot to come to an agreement about how to proceed.
"It was shocking and a little disappointing," Jeri Lacks Whye said of hearing of published sequence. She said Skloot contacted the family to ask if they'd given consent for the publication. "It's like her medical records were just there for anybody to view with a click of a button. it seemed like history was repeating itself." 
Other Lines, Other Sequences
Steinmetz and his colleagues were not the first to consider sequencing the cell line. In November 2012, before Steinmetz published his paper, Jay Shendure and colleagues at the University of Washington gave a presentation at the annual meeting of the American Society for Human Genetics (ASHG) in San Francisco, California, detailing the sequencing of HeLa cells.
“We sequenced the HeLa genome to ~88X shotgun coverage in order to accurately identify variants in the context of extreme aneuploidy. Next, we constructed and sequenced nearly 300 fosmid clone pools, each containing ~2 percent representation of the genome, thereby providing islands of haplotype-specific coverage,” the group’s ASHG abstract reads. “The genome of HeLa may yield insights into the biological basis for its persistence and robust growth properties.”
Following the March response to the Steinmetz paper, Shendure and his colleagues declined to comment or share their work although it had already been accepted for publication by Nature. 
Collins applauded the "patience" of Shendure and Nature in waiting until an agreement was made with the Lacks family before publishing the findings. Shendure and his team published a whole genome analysis of the CCL-2 strain of HeLa cells in Nature today, piecing together the complex, rearranged genome of the HeLa cells and identifying an insertion of the human papillomavirus near an oncogene that may explain the aggressiveness of Lacks’ cancer.
The findings present a "level of detail" previously not seen, Collins said. One recurring critique is that the HeLa cell lines that exist today may bear little resemblance to Henrietta Lacks. 
"There are many different lines that have been growing independently," Collins explained today. "Maybe there is no one HeLa anymore." However he reported that the Shendure lab compared two particular lines that had been separated since 1955. "They are quite similar at the DNA level," Collins said. "HeLa doesn't seem to have picked up a lot of lab-acquired mutations. It looks remarkably stable other than changes that happened right at the beginning." 
“The HeLa genome is another chapter to the never ending story of our Henrietta Lacks,” said Henrietta’s granddaughter Jeri Lacks-Whye and Lacks family spokesperson. “She is a phenomenal woman who continues to amaze the world. The Lacks family is honored to be part of an important agreement that we believe will be beneficial to everyone.”
Shendure's paper today acknowledges and thanks the contributions of the Lacks family.