What does the Hela genome agreement imply for consent and genome data usage?

All opinions my own and do not necessarily reflect those of Novo Nordisk.

A fair amount of reporting (for example here, here and here) has gone into the recent news that the NIH and the descendants of Henrietta Lacks have reached an agreement about the conditions under which the genome sequence of the HeLa cell line will be shared.  The basic parameters are that researchers wanting access to the data will need to apply for permission, the application committee will include members of the Lacks family, any publications will acknowledge the contribution of the Henrietta Lacks, and future genome sequences will be submitted to dbGAP.

This is a generally welcome development, and in no small part due to the work of Rebecca Skloot.  Her book, The Immortal Life of Henrietta Lacks provided the impetus to the current developments by popularizing the story of Ms. Lacks and the cell line derived from her tissues.  However, this agreement also can be seen as a precedent of sorts, and the future implications for the ethics of consent, genetic information sharing and genomic research are unclear.

Whose genome is it, anyway?

In Pasco Phronesis, David Bruggeman penned a post on some of the possible implications.  He discusses one of the key elements of genetic consent that I generally haven’t seen elaborated on much in the current literature: familial consent and exposure.   To what extent do those who share part of a sequenced genome have a say in the granting and rescinding of consent for the usage of genetic information?  

On the one hand, as he points out, the HeLa case may be special given the origins of the HeLa cell line.  But on the other hand, the key element is shared identical genome sequence information, which will be a factor in every genome sequencing endeavor.  Every child shares 50% of his or her exact genome sequence with each biological parent and vice versa.  In the uncommon case of identical siblings, 100% is shared.   Non identical full siblings share, on average, 50% as well.  This means that any research, any inferences, any genetic findings that arise from the sequencing of a given genome have implications not just for the individual who consented but for all of that person’s relatives.  In addition, the amount of genetic information is much larger than would be obtained from single gene tests for specific conditions, meaning the scope of possible findings is unknown and unpredictable.

It’s interesting that even in very forward-looking genome sequencing endeavors such as the  Personal Genome Project it still appears that consent is viewed on a primarily individual basis, despite the shared familial implications.  A look at their consent form shows an admirable openness about the lack of privacy that would come from participation, and does explicitly state some of the possible unintended results for families upon public release of the genome sequence information, such as exposure to the press.  However, the only time family consent is mentioned is in the context of living identical siblings, where it says the explicit consent of those siblings is needed.

This would be fine if personal genomes truly were personal.  But as I’ve described, genomes are shared, not personal, and research on genetics provides many examples of gene variants that have a clear functional role and therefore clear implications for those sharing the variant.   Maybe a subject learns he or she is homozygous for a variant in PCSK9 that results in abnormally low LDL levels.  This would be one of those happy findings that would have positive implications for that person’s parents and children.  On the other hand, maybe the finding is that the subject has a variant in an oncogene that predisposes him or her to cancer.  Would that person’s parents or children want to know that they may be carriers of the same risk?

So is the answer to follow a process such as is being modeled for the HeLa genome, in which family members are involved in decisions regarding the release of genome sequence information of any family member?  As David Bruggeman points out, where does one draw the line?  Immediate family?  First cousins?  First cousins share on average 12.5% of a genome, which doesn’t seem like much but still represents a few thousand genes.  It’s a difficult question in part because the actual risks are still hypothetical, making it hard to estimate the real damage that could occur.   This is a needed component of assessing where to draw an ethical line.  There are also the practical implications of how to do this, since there are currently thousands of immortal cell lines, and is it ethical to provide this kind of agreement to the family of just one of them?

This is also the tip of the iceberg as far as the breadth of people who will eventually be affected.  The current state of genome sequencing is that it is still largely done under the auspices of a research program, and much of the literature surrounding the ethical considerations for communication of genome information are being hashed out in that context.  It’s common practice in these studies for medical doctors and geneticists to be involved and, whether incidental genetic findings are communicated to subjects or not, there is generally due consideration of the issues of consent and impact on the subject and the subject’s family.

However, now 23andMe is releasing their first TV ad campaign.  Numerous people have already participated and spit, and it’s been fun and interesting and novel, but a TV ad kicks it up several notches.  The more people you reach, the more chances there are that genome sequence information will be released into the public domain despite the contrary wishes of those who share some of that exact DNA sequence.  For a long time I’ve been thinking that the American College of Medical Genetics, the American Medical Association, and other interested groups should have been banging the drum harder for increased training of genetic counselors.  I think it’s an occupation we’re really going to need more people in, really soon.

I never got my scientist card…

On a completely unrelated note in this whole HeLa story, I can see some problems on the implementation side for the restrictions to access to the HeLa genome.  I know this was a throwaway line in the interview The Scientist did with Rebecca Skloot, but when she mentions how only “card-carrying scientists” will be able to request access, I found myself saying “What?” The announcement from the NIH makes the same point, saying only biomedical researchers will be able to apply to see the sequence.  But what does that mean?  Does that cover AP Biology students who want to study the genome as a tool for understanding immortalizing mutations?  How about a DIY bio researcher who has her own lab in her garage?   Seems a  bit vague.

In addition, NIH touches on a more fundamental issue about restrictions.  Namely, why does anyone need to bother with NIH at all?  If you really want the sequence, order the cells from ATCC, extract the DNA and send it off to one of the many DNA sequencing providers.  The analysis can be done rapidly with available, commercial software tools.  As Kathy Hudson told Science, “We are aware that any lab with the right equipment can sequence the genome without permission.”  Francis Collins has stated he believes the bulk of researchers will follow the spirit of this agreement, even if they do not receive NIH funding.  I hope he’s right.  I suspect he’s wrong.

I’m not saying the restrictions are bad. On the contrary, they’ve raised awareness, they are symbolic, and they are the right thing to do.  But there needs to be more done and thought and implemented and preferably soon.  This isn’t like the days of the Asilomar Conference on Recombinant DNA, where only a handful of labs across the world had the equipment, experience and expertise to use the new tools of molecular biology and therefore could effectively choose to stop and start research in the field.  Despite the recent announcement by  many prominent genomics organizations about a global alliance for data sharing, there isn’t the same ability to control what happens in the field of genomic research.

We live in a very distributed, very information-rich world in which the barriers to creation and research are far lower than they have ever been.  The question is what kinds of tools, policies, laws, conventions, and environments should we put into place to try and minimize the potential hazards of genetic data sharing while still trying to maximize the benefit to human health and well-being.

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2 thoughts on “What does the Hela genome agreement imply for consent and genome data usage?

  1. Great post! I find the “controlled access” question particularly intriguing: according to their guidelines only researchers are allowed to apply. Isn’t that somewhat at odds with the NIH’s general policy to make publications from NIH-funded research available to the general public?

    • Thanks for taking the time to check out the post. This is a real question–where to draw the line between public and individual rights. If you were to ask anyone at NIH or in Congress whether NIH funded research should be made publicly available, including raw data, I think the knee-jerk reaction would be “of course! The people of the US have paid for that data and should be able to access it.” But things are never so black and white, and in the case of genome sequences there are strong privacy implications that put it into a different category, I think. It’s similar in some ways to the debate that’s gone on about publishing the results of experiments about mutations that make flu strains more likely to become airborne. This is important research; it should be funded and performed, but there are public health and safety implications to publishing the results.
      The NIH Open Access Policy (http://publicaccess.nih.gov/policy.htm) specifically refers to a publication being made available and not necessarily the raw data. But I think that’s implied, since many journals have a policy that data should be available in a public repository prior to publication. However, I think other interests such as patient privacy can be invoked to counter those policies. On a practical level, I also think the journals don’t actually spend a lot of time and effort in making sure data is deposited somewhere and is complete. It’s a lot of work.

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