A team from the University of Washington has unveiled a comprehensive portrait of the genome of the world's first immortal cell line, known as HeLa. The cell line was derived in 1951 from an aggressive cervical cancer that killed Henrietta Lacks, a 31-year-old African-American tobacco farmer and mother of five -- the subject of the 2010 New York Times bestseller, The Immortal Life of Henrietta Lacks. They will also be the first group to publish under a new National Institutes of Health (NIH) policy for HeLa genomic data, established through discussions with Lacks' family.
The Lacks' family has never been compensated for the use of the cells that created a multimillion-dollar industry. And they have never had a say in how the information is used -- until now.
"The generated whole-genome sequence of the HeLa cell line is a valuable resource that may lead to new biomedical insights based on research that use these cells," said Eric D. Green, director of the National Human Genome Research Institute within the NIH. "We are grateful to the Lacks' family for agreeing to a framework that makes these valuable data available to researchers."
The UW study, published in the Aug. 8 issue of Nature, pieced together the complicated insertion of the human papillomavirus (HPV) genome, which contains its own set of cancer genes, into Lacks' genome near an "oncogene," a naturally occurring gene that can cause cancer when altered. The researchers showed that the proximity of the scrambled HPV genome and the oncogene resulted in its activation, potentially explaining the aggressiveness of both Lacks' cancer and the HeLa cell line. "This was in a sense a perfect storm of what can go wrong in a cell," said Andrew Adey, a PhD student in genome sciences 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."
Scientists had long tried to reproduce cells in a culture, but they eventually died. The HeLa cells -- taken from Lacks in 1951 -- however, reproduced an entire generation every 24 hours and never stopped.
HeLa cells have since been named in nearly 76,000 PubMed abstracts and are considered one of the biggest medical miracles in the last century. The cells allowed scientists to perform experiments without using a living human and led to major medical breakthroughs, including the polio vaccine, cloning and helping develop drugs for treating major illnesses such as herpes, leukemia, influenza, hemophilia and Parkinson's disease.
Just why Lacks' cells replicated in a culture where others never could has been a mystery.
The authors said their study might explain -- at least in part -- why HeLa is unique. In addition, they discovered that the genome of the HeLa cell line, which has been replicated millions, if not billions of times, has remained relatively stable. They also said their results can help other researchers investigating cancer by studying immortalized cell lines.
"We demonstrated the value of comprehensive analysis -- through what are called haplotypes -- in characterizing cancer genomes and epigenomes," said researcher Jay Shendure, a UW associate professor of genome sciences and senior author of the paper in Nature, "The haplotype-resolved genome and epigenome of the aneuploid HeLa cancer cell line."
Haplotypes, in short, provide a more complete description and interpretation of genomes, genetic diversity and genetic ancestry, by separating out which genetic variations are present on each copy of each chromosome.
Although individual human genome sequencing is increasingly routine, nearly all such genomes are unresolved with respect to haplotype. In this study, haplotypes were crucial for revealing the initial events that drove Lacks' cancer.
Agreement with family
To publish their study in Nature, the UW team needed to make their data available to other researchers. And this is where the NIH, the funder of the study, intervened and initiated discussions with Lacks' family.
The genome -- a string of billions of letters that detail the genetic information that makes up a HeLa cell -- can be translated into personal genetic information, such as a person's propensity to develop a disease, including alcoholism, Alzheimer's and bipolar disorder.
In March, a team from Europe sequenced the genome of a different HeLa strain, publishing the results and depositing the data in a publically accessible website. This lead to scientific outcry sparked by an op-ed in The New York Times by the book's author Rebecca Skloot.
"Imagine if someone secretly sent your DNA to one of many companies that promise to tell you what your genes say about you," Skloot wrote in the March 23 editorial, The Immortal Life of Henrietta Lacks, the Sequel. "Now imagine they posted your genetic information online with your name on it."
Skloot noted that life insurance, disability coverage and long-term care can discriminate against people for certain conditions.
The European group later apologized and took down the data.
The controversy pushed the NIH into setting standards, which will be announced Aug. 8 as well.
The NIH met with members of the Lacks' family and two members will now be sitting on an advisory committee within the NIH to grant approval, said Larry Thompson, chief of communications at the National Human Genome Research Institute within the NIH.
He said the younger generation of the Lacks' family realizes that the technology has advanced so much that anyone can now sequence the cells to get genetic data.
"There's no way to put the genie back in the bottle," Thompson said.
Wylie Burke, a renowned bioethicist and chair of UW's Department of Bioethics and Humanities, said the NIH has done a great thing to reach out to the Lacks' family and understand their concerns. She said many people probably don't understand what it means that their genetic data will be available in a federal repository.
"We can't do research without participants giving their materials," she said. "We've done focus groups and people want to understand how data is going to be used. They value that opportunity to contribute but want to be respected."
Other researchers who contributed to this work include co-first authors Jacob Kitzman and Joshua Burton, and Joseph Hiatt, Alexandra Lewis, Beth Martin, Ruolan Qiu and Choli Lee.
This project was made possible through support from the National Institutes of Health and the Washington Research Foundation.
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