Monday, August 26, 2013

Henrietta Lacks' Immortal Cells

This month brought some progress to the family of Henrietta Lacks, whose cells were collected more than fifty years ago while Lacks suffered from cervical cancer. The resulting HeLa cell line has been critical for the development of cell culture, the generation of the Polio vaccine and many other important scientific discoveries. Recently, the genome sequence of HeLa cells was published online, a development that concerned Lacks' family members. As of this writing, the NIH has agreed to include two members of the Lacks family in the decision making process for the future use of the cells (check here and here for coverage of varying depth). The agreement does not result in any remuneration for the family. While this agreement is a clear step forward, this is still an isolated case and has not set a standard for consent about the use and sharing of genomic data.

I wanted to write something about this event because it brings the excellent book by Rebecca Skloot back into my mind. The Immortal Life of Henrietta Lacks is definitely near the top of my list for best science books; this list includes books by Stephen Jay Gould and Carl Sagan. Skloot has received many accolades, and with good reason. The book does an amazing job of laying out the history of a complex story in an easy, digestible way and she makes the story compelling. The book was written in such a way that you feel the thrill of the investigation, as well as an emotional connection to the Lacks family. Skloot was careful not to place blame on the scientists involved. Rather, she presents the issues surrounding the case with the professionalism and rigor of a journalist, rather than someone trying to sensationalize the case, which is certainly easy to do in a situation like this, where the patient was a poor, African-American woman whose cells were taken without permission (at the time, there was no standard for informed consent).

Henrietta Lacks was infected with both human papillomavirus (HPV) and syphilis (probably by her husband), which were likely the cause of and a contributing factor to the aggressiveness of her cervical cancer. Now, several groups of researchers are sequencing the genome from HeLa cells to pinpoint what made HeLa cells grow so robustly. In a paper published in the August 8 edition of Nature, Adey and colleagues report that the HeLa genome is hypertriploid (meaning that the cells had just over three sets of chromosomes, whereas healthy cells would have two copies; aneuploidy or abnormal chromosome numbers is a hallmark of cancer cells), has a surprisingly low rate of point mutations during the course of normal cell culture, and has had a fairly stable chromosome count since the initial isolation of the cells. Most interestingly, the study describes the insertion of the HPV genome at a fragile site on one copy of chromosome 8. Only two thirds of the HPV genome was observed at chromosome 8; importantly, copies of the E6 and E7 oncogenes of the HPV genome were integrated. These oncogenes have been linked to cervical cancer progression, malignancy, and cell immortalization. Notably, the sequence for E2, the inhibitor of E6 and E7, was absent. Finally, the site of HPV integration was 500 kilobases from MYC, a canonical proto-oncogene; MYC showed very high expression, but only from the copy of chromosome 8 that included the HPV genome. Essentially, the oncogenes from HPV were hyper-activated, as was the MYC oncogene from the HeLa genome and this was directly caused by the insertion of HPV near the MYC oncogene. Thus, the research suggests that the interaction between the HPV DNA and the HeLa DNA may underlie the robust growth characteristics of the HeLa cell line. These results are exciting and suggest that we still have a lot to learn about HeLa cells. 

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