HeLa genome sequenced w/o obtaining permission/consent from family – some comments and background

Last week David Coil in my lab reminded me that he had been wanting to borrow a copy of “The Immortal Life of Henrietta Lacks” by Rebecca Skloot.  I have read the book many many times and had told David I even had a preprint that Skloot or her publicist sent me before the book came out (I did not know Skloot then – I just got it because of my blog).  As I went to grab the preprint off my shelf in my office he said he wanted to read it know because the genome of the HeLa cells which had been taken from Mrs. Lacks had been published a few days before.  I was shocked.  I asked him if he knew if the authors of said paper had gotten consent before publishing it.  So I opened a web browser and googled and found the paper and some news stories and a press release from the group who did the sequencing.

Holy fuck.  They did not seem to have permission.  Uggh.  I had thought about this a lot because a few years ago I was thinking of writing a review of “The Immortal Life of Henrietta Lacks”. As part of that started to write about the possibility of sequencing the HeLa genome and what that might mean.  I also did an April Fools joke relating to the topic: http://therealhela.blogspot.com.  And every time new sequencing technology comes along I have thought about – and discussed with others – the possibility of sequencing the HeLa genome.  And every time I got to this point I decided that it would be unethical, inappropriate, and downright stupid to do this without consent.  Note – my original plans for the book review involved a focus on the strange balance between openness and sharing in the history of HeLa and the lack of consent (e.g., see this blog post).

I was so angry about the lack of consent here that I took to Twitter.


And after that there was remarkably little discussion of the issue by others. What the fuck? People get up in arms about all sorts of minor things so why not get up in arms about this? Where were all the supposed genomic ethicists out there? How did this happen? Thankfully, yesterday a piece on the topic came out from Rebecca Skloot (it was in this mornings New York Times) and it has launched this issue into a much more public discussion. So much discussion that I decided to storify it. See below.

//storify.com/phylogenomics/hela-genome-sequenced-w-o-consent.js[View the story “#HeLa genome sequenced w/o consent (by Jonathan Eisen)” on Storify]

Lots of discussions going on out there. And I think Rebecca deserves credit for writing this piece and bringing the story out more. I tried to get people going on Twitter and it was a slog — people did not seem that interested to be honest. Now – everyone seems interested. Including some who say they agree with Rebecca (and me) that it was a mistake to publish this genome.

Alas, am wondering what these people thought before the Skloot article. Why did so many people just stand by and say nothing? Too busy? Did not occur to them that this could be an issue? Or something else.  Oh – and why did it not occur to Francis Collins and all the people behind encode that this could be an issue. They published a lot of genomic data from HeLa cells and never once asked for consent or apparently even thought about it.

Anyway – it’s about time we as a community got off our butts and started discussion how to deal with the ethics of personal genome data.  This data will be coming out more and more.  We need to figure out how to handle it and the consent issues around it.  And we also need to do a better job of figuring out what to do with samples for which consent was not given but which are used.  Should we stop using HeLa cells?  Possibly.  If we want consent to use them – who will give it?  I don’t know the answers.  But I do know one thing – science should not simply proceed forward just because these questions are hard to answer.  Publishing the genome without consent or talking to the family was a very very very bad idea given that the ethical issues around consent here are murky.

UPDATE – 5 PM 3/24/13

Adding some notes about the press release and genome publication
Genome paper: – some key quotes of interest
  • Abstract
    • “To date, no genomic reference for this cell line has been released, and experiments have relied on the human reference genome”
    • “Our results provide the first detailed account of genomic variants in the HeLa genome, yielding insight into their impact on gene expression and cellular function as well as their origins.”
  • Results
    • “produced nearly 1 billion reads of length 101 nt” (thus they produced 101 billion bases of DNA sequence information).
    • The read data are available in the European Nucleotide Archive (ENA) database under the accession number ERP001427. 
    • We report a compendium of genomic variation (CN, SNVs and SVs) as well as the first HeLa genome draft, which are available as VCF and FASTA files respectively 
    • We provide a tool to perform the translation of coordinates between GRch37 and our HeLa reference, 
    • Most variants in these HeLa cells thus represent common variants in the human population. The African-American population (to which Henrietta Lacks belonged) is spread between the African and European clusters, with the HeLa sample overlapping both. This demonstrates that although the genomic landscape of HeLa is strikingly different from that of a normal human cell, the population-specific SNV patterns are still detectable. 
  • Discussion
    • Since the establishment of the HeLa cell line in 1952, it has been used as a model for numerous aspects of human biology with only minimal knowledge of its genomic properties. Here we provide the first detailed characterization of the genomic landscape of one HeLa line relative to the human reference genome 
Original press release (a copy of which I found here)
  • “The results provide the first detailed sequence of a HeLa genome,” explain Jonathan Landry and Paul Pyl from EMBL, who carried out the research. “It demonstrates how genetically complex HeLa is compared to normal human tissue. Yet, possibly because of this complexity, no one had systematically sequenced the genome, until now.”
  • “The HeLa genome had never been sequenced before, and modern molecular genetic studies using HeLa cells are typically designed and analysed using the Human Genome Project reference. This, however, misrepresents the sequence chaos that characterises HeLa cells, since they were derived from a cervical tumour and have since been adapting in laboratories for decades.”
  • “The study provides a high-resolution genetic picture of a key research tool for human biology. It highlights the extensive differences that cell lines can have from the human reference, indicating that such characterisation is importahttp://www.nytimes.com/2013/03/24/opinion/sunday/the-immortal-life-of-henrietta-lacks-the-sequel.html?_r=0nt for all research involving cell lines and could improve the insights they deliver into human biology.”
  • Can we infer anything about Henrietta Lacks or her descendants from this sequencing?
    • No, we cannot infer anything about Henrietta Lacks’ genome, or of her descendants, from the data generated in this study. Firstly, the subtype of HeLa cells sequenced in this study has spent decades in labs, dividing and thus undergoing mutations and changes – they are very different from the original cells that started growing in 1951. Secondly, these initial HeLa cells were taken from Henrietta Lacks’ cervical cancer tumour – as cancer is a disease of the genome, the DNA of cancer cells is usually different to that of the patient. Without any genetic information from the http://www.genomeweb.com/blog/learnt-lessonsoriginal tumour or from Henrietta Lacks, it is impossible to distinguish which parts of the genome sequenced here originate from Mrs. Lacks, her tumour, or laboratory adaptation. The goal of this study was not to gain insights into Henrietta Lacks’ cancer or personal biology, but rather to provide a resource for researchers using HeLa cells.

UPDATE 3: 11: 40 PM 3/25/13 Presidential Commission

Rebecca Skloot has unearthed a report from the Presidential Commission on for the Study of Bioethical Issues which few people seem to have been aware of (I have heard nothing about it). 

The report was release on October 2012 but got very very little coverage and I have never seen/heard it mentioned anywhere. But it covers a lot of ground of direct relevance to this HeLa story. The whole report is available here. Here are some choice statements (bolding by me)

“Large-scale collections of genomic data raise serious concerns for the indi- viduals participating. One of the greatest of these concerns centers around privacy: whether and how personal, sensitive, or intimate knowledge and use of that knowledge about an individual can be limited or restricted (by means that include guarantees of confidentiality, anonymity, or secure data protec- tion). Because whole genome sequence data provide important insights into the medical and related life prospects of individuals as well as their relatives who most likely did not consent to the sequencing procedure—these privacy concerns extend beyond those of the individual participating in whole genome sequencing. These concerns are compounded by the fact that whole genome sequence data gathered now may well reveal important information, entirely unanticipated and unplanned for, only after years of scientific progress.”

“Whole genome sequencing dramatically raises the privacy stakes because it necessarily involves examining and sharing large amounts of biological and medical information that is not only inherently unique to a single person but also has implications for blood relatives. Genomic information is inherited and determines traits like hair and eye color. Unlike a decision to share our hair or eye color, which does not reveal anything about our relatives that is not observable, a decision to learn about our own genomic makeup might inadvertently tell us something about our relatives or tell them something about their own genomic makeup that they did not already know and perhaps do not want to know. More than other medical information, such as X-rays, our genomes reveal something both objectively more comprehensive and subjectively (to many minds) more fundamental about who we are, where we came from, and the health twists and turns that life might have in store for us.”

Because whole genome sequence information directly implicates relatives, psychological harms often are not limited to the person whose genome is voluntarily being sequenced and publicly disclosed. Even individuals who learn that they do not carry a harmful variant may experience “survivor’s guilt” if another family member is affected.”

“At the same time, individuals have a responsibility to safeguard their privacy as well as that of others, by giving thoughtful consideration to how sharing their whole genome sequencing data in a public forum might expose them to unwanted incursions upon their privacy and that of their immediate relatives. To be indifferent to the implica- tions of disclosure of sensitive data and information about one’s self is to act irresponsibly. That being said, it can be good and virtuous to share sensitive data about oneself in appropriate circumstances, for example, for the good of public health research or public education.”

Risks might also fall to blood relatives of these individuals who carry similar genomic variants, thereby raising the stakes of privacy concerns in whole genome sequencing compared with most other types of research.”

UPDATE 4: 3/26/13 – Some new stories / links

UPDATE 5: 3/26/13 – Rebecca Skloot on Morning Edition

UPDATE 6: 3/26/13 – Some more stories / discussion

UPDATE 7: 3/26/13 2 PM PST Still waiting for ENCODE to say something about whether they are going to take down their #HeLa data. See for example my Tweet from a few days ago




Fun with Pubmed central – first paper describing #HeLa cells – Note @rebeccaskloot

Last year, Rebecca Skloot came to Davis to talk about her book “The Immortal Life of Henrietta Lacks“.  Note – if you have not read the book – what f*$ing rock have you been hiding under?  It is in my opinion the best non fiction book I have ever read.  Seriously.  Not the best science book. The best non fiction book of any kind.  And I am not alone in this feeling as it has won a bazillion positive reviews and awards.   In summary – it tells three stories – the story of the isolation of HeLa cells, the story of the woman from whom those cells came, and the story of Skloot learning the other two stories.

Anyway – I somehow managed to get her to come to UC Davis to give a talk last year just as the book was going viral.  In preparation for Skloot’s visit I decided to do some sort of “open access” schtick and looked into how many papers about HeLa cells were in Pubmed Central.  Pubmed Central is a database of papers for which the full text is available at no charge.  After this mini-research and after interacting with Rebecca over the last year and seeing the well deserved recognition of her book, I have been a bit fascinated about how much of the literature surrounding studies of HeLa cells is openly and/or freely available.

So today I decided to see what was the earliest HeLa paper that was freely available on PubMed Central.  And I managed to find a good one: Studies on the propagation in vitro of poliomyelitis viruses. IV. viral multiplication in a stable strain of human malignant epithelial cells (strain hela) derived from an epidermoid carcinoma of the cervix. William F. Scherer, Jerome T. Syverton, and George O. Gey.  J Exp Med. 1953 May 1; 97(5): 695–710.

I believe this was the first full paper published discussing HeLa cells.  Nice short title by the way. Anyway – good to see it in Pubmed Central.

I note  – I could not find in Pubmed Central the meeting abstract about HeLa cells which was published in 1952 but I did find it from Cancer Research’s online archive here.  I have copied the abstract below, for you HeLa history buffs out there:

LIUM. George O. Gey,Ward D. Coffman*
and Mary T. Kubicek *(Departments of
Surgery and Gynecology, Johns Hopkins
Hospital and University, Baltimore 5, Md.

This is a report of an evaluation in vitro of the
growth potential of normal, early intra-epithelial,
and invasive carcinoma from a series of cases of
cervical carcinoma. Comparable cytological and
tissue culture studies were actually carried out on
selected biopsies of normal and neoplastic areas of
the same cervix. Thus far, only one strain of epi-
dermoid carcinoma has been established and
grown in continuous roller tube cultures for al-
most a year. It grows well in a composite medium
of chicken plasma, bovine embryo extract, and
human placenta! cord serum. The autologous nor-
mal prototype is most difficult to maintain under
comparable cultural conditions. Most of the tissue
from other cases showed rapid keratinization of
the cells grown in cultures whether from normal
or neoplastic areas. Some of the hormonal aspects
of the problem will be discussed.

Anyway – if you are interested in HeLa and/or The Immortal Life of Henrietta Lacks, you may find it interesting to check out these early papers on the topic such as the ones described above.  Here are a few more that are from the early era and are freely available:

Pubmed Central is a rich resource not just for accessing scientific papers but for learning about science history too.  It is a good thing that articles in Pubmed Central are available at no charge and here’s hoping that sometime soon that past and present and future science papers will be more readily available to all.

John Hogenesch from U. Penn made a nice figure of relevance and agreed to let me post it:

And he comments “You can see several things, Nixon’s “war on cancer” in the early 70s and the dawn of the cell/molecular biology age in the 80s and expansion in the 90s.”

Thanks John …