NEW YORK (GenomeWeb News) – Officials from the National Institutes of Health and the family of Henrietta Lacks have together developed a policy for allowing researchers to access whole-genome data from HeLa cell lines, which was outlined today in Nature.
"This agreement will protect the family's interest and advance our shared commitment to biomedical research," NIH Director Francis Collins said during a telebriefing with reporters today.
Two characterizations of the HeLa genome, one from a German group and new one from a team in the US, are now available in an access-controlled database.
HeLa cell lines were developed from a biopsy taken from Henrietta Lacks, a 31-year old African-American woman, while she was being treated for an aggressive case of cervical cancer at the John Hopkins Hospital in Baltimore in 1951. The cells were taken and shared without her knowledge or permission — consent regulations had yet to be developed in the US — and they subsequently were developed into a number of cell lines. Lacks' identity was also revealed.
HeLa lines have been in extensive use by researchers worldwide and have played a role in vaccine research, the development of cancer therapies, and the rise of in vitro fertilization techniques.
Because of this wide and frequent use of HeLa cell lines, researchers have been interested in exploring the HeLa genome.
Earlier this year, a group of researchers from the European Molecular Biology Laboratory published the online, early version of their G3: Genes Genomes Genetics paper examining the genome and transcriptome of the HeLa Kyoto cell line. By combining DNA and RNA sequencing of that line, the researchers, led by EMBL's Lars Steinmetz, found that the HeLa genome was replete with structural variations, such as chromothripsis, and differential gene expression patterns, including of cell cycle and DNA repair pathways.
As part of publishing their paper, the EMBL team made the genomic data of the HeLa cell line publicly available
That led to criticism from other researchers, bioethicists, and patient advocates, as well as concerns from the Lacks family.
"The main issue was a privacy concern and what information in the future that will reveal," said David Lacks, Jr., Lacks' grandson, during the press event today. "Right now we are in the early stages of genomic research and genomic medicine, so we don’t know what is going to come along down in the future or what type of privacy concerns we'll have."
Upon hearing concerns from the Lacks family, the German researchers and the editors of G3 quickly removed the data from the data from public access.
As Collins noted, two values of biomedical research community came into opposition: the public sharing of data and respect for research participants.
In the wake of this event, NIH worked with the Lacks family to develop a way for researchers to access the HeLa genome while addressing the family's concerns. Collins and Kathy Hudson, the deputy director for science, outreach and policy at NIH, met with Lacks family representatives on three occasions to discuss the options: making it freely accessible, putting it into a controlled-access database, or removing it from public use. Some family members also met privately with an NIH genetic counselor.
As Collins and Hudson wrote in Nature, the family members unanimously chose the controlled-access option.
Under this new policy, any NIH-funded investigator who wishes to use HeLa whole-genome sequence data will have to apply to the agency and agree to the terms of the HeLa genome data use agreement, including depositing any future whole-genome sequence data generated from HeLa cells into the controlled-access database. The agency also encourages researchers to acknowledge in their papers and presentations the contribution of Lacks and her family.
NIH has set up a six-member HeLa Genome Data Access working group to govern access to the sequence data. That group will include scientists, physicians, a bioethicist, and two members of the Lacks family.
"Through their participation in the working group, the Lacks family is in the loop and at the table," Hudson noted during the briefing.
The German research team and a group from the University of Washington, which has examined a separate HeLa line, have submitted their data to the controlled-access database, which is part of the Database of Genotypes and Phenotypes.
Collins and Hudson noted that as there are pieces of the HeLa genome spread throughout the scientific literature, it could be pieced together without going through the controlled-access process, and, researchers not funded by NIH could still sequence the HeLa genome. But they urged the community to "act responsibly and honor the family's wishes."
"Downloading the HeLa sequence through controlled access is the right and respectful thing to do," Collins and Hudson said.
The new HeLa genome paper, also in Nature this week, from Jay Shendure, an associate professor of genome sciences at UW, found that the HeLa cell line, despite all its passaging in culture, has been rather stable.
The UW group sequenced the HeLa CCL-2 strain, using a combination of shotgun, mate-pair, and long-read sequencing using the Illumina HiSeq 2000 to 88x coverage.
From that, they generated a haplotype-resolved sequence of the cell line, which they compared to that of HeLa S3, which separated from the CCL-2 line in the early days of the HeLa cell lines, and to that of eight other strains — which they said they "lightly" sequenced to about 4x coverage, finding few changes between the lines. This suggested to Shendure and his colleagues that the HeLa line has remained fairly stable over the years.
They noted, though, that getting haplotype resolution enabled them to uncover an amplified and highly rearranged region on chromosome 8. This spot at 8q24.21, which is right near the MYC oncogene, is likely a site of human papillomavirus-18 integration, the researchers added.
Adding in information from RNA-seq and ENCODE project datasets indicated haplotype-specific activation of the oncogene due to the viral integration. This, the researchers hypothesized, could explain why Lacks' cancer was so aggressive.
"This was in a sense a perfect storm of what can go wrong in a cell," said Andrew Adey, a PhD student at UW and a co-first author on the study. "The HPV virus inserted into her genome in what might be the worst possible way."