I knew I wanted to be a part of Genomes Unzipped from the very first day Daniel told me about the project. But the decision to actually participate was more complicated.
I’ve spent a lot of time over the past five years thinking about the benefits and risks of personal and public genomics. By sheer good luck I became an advisor to the Personal Genome Project (PGP) in its early days, long before PGP-1 (George Church) was joined by so many others (the arrival of the PGP-1K was announced yesterday) interested in exploring public genomics. As a result of that connection, I have been able to continue to work with the PGP, exploring the issues raised by public genomics research as they arose, often for the first time, in connection with that project. And as part of my day job I edit an online publication (the Genomics Law Report) and advise clients—both focused on issues arising at the intersection of personalized medicine, genomics and the law.
As a result of all of this time spent thinking and writing about personal and public genomics, I’ve come to know a few things. I know that I believe the benefits of public genomics, for both science and society, to outweigh the risks. I also know that I might be wrong about that, but I know that I’m comfortable accepting that risk, too. I know that I want to support personal and public genomics projects. Most of all, I know the decision to join a project like Genomes Unzipped is not mine alone.
Before agreeing to participate in Genomes Unzipped, I knew I would need to seek—and receive—permission from my family. There was no legal requirement that I obtain their consent before joining the Genomes Unzipped team and, ultimately, publishing my genetic data for the world to review. But that did nothing to change the strong personal obligation I felt to seek my family’s consent.
While my genetic information is personal to me, it could also have something important to say about my family members. The strong likelihood was that it would not, particularly once you diluted the limited predictive value of most genetic markers with a hefty dose of uncertain utility and a large helping of additional uncertainty thanks to the fact that I share, on average, only 50% of my genome with each of my family members. But while I could calculate that risk as small, and accept it for myself, I could not unilaterally accept it on behalf of each member of my family.
Knowing that, I set out to talk to my family about Genomes Unzipped and my interest in participating in the project, and to learn whether that was a decision they would each be willing to support. Spoiler alert: there is no surprise ending here. You would not be reading this post if any member of my family had not fully supported my decision to join Genomes Unzipped.
Still, I learned a great deal from the process of seeking informed consent from my family for my participation in Genomes Unzipped. And as the cost of genomics sequencing continues to decline, and more genomic data inserts itself in more ways into more of our lives, conversations like this will become more common. More of us will want, or need, to talk with our families about genetics, including the potential risks and benefits of sharing our genetic data with others (and, for some, with the whole world).
Last November, I sent the email below—which has been reproduced verbatim and with permission, with only names and email addresses redacted—to my parents , brother and sister shortly before we gathered in North Carolina for the Thanksgiving holiday. I hope that it, along with this post and several more that will follow in the coming weeks from me and my Genomes Unzipped colleagues, will serve as a helpful starting point for a discussion about how to talk and think about familial informed consent in the context of public and personal genomics.
From: Vorhaus, Daniel
Sent: Monday, November 23, 2009 2:00 PM
To: [Mom]; [Dad]; [Brother]; [Sister]
Subject: A family discussion about public genomics
Dear Family –
We’ve talked in the past about my work with the Personal Genome Project (PGP) and the possibility that I might be asked to participate in that project at some point by making my genetic information publicly available for research purposes.
I still have no plans to publish my genetic data through the PGP. However, I have been advising a different group of researchers (in Cambridge, UK) and they have asked if I would be willing to publish portions of my genetic information through that project (which is called “Genomes Unzipped”). I’m writing because I would like to say “yes,” but I first want to make sure that each of you is OK with the decision.
Below I’ve attempted to describe what I would be doing, why I’d like to do it and what that might mean for each of you. It’s a little bit long, I know, and I apologize for that. If it’s any consolation, knowing me it could have been much, much longer. I’m hoping that you’ll each be able to find time to read it and that we can talk about any questions or concerns that you have when we’re all together this week. In any event, I will wait to speak with all of you before I respond to the team from Genomes Unzipped.
Without further ado…
I What genetic information would be published?
The information that I would publish, at least at first, would be information generated by the company 23andMe (http://www.23andMe.com/). You can see a list of the traits for which they generate information here. It’s important to keep in mind that the information generated by 23andMe is not a complete genome sequence (all 6 billion base pairs). What they do is genotype (or “read”) several hundred thousand letters in an individual’s genome that are thought to be associated with certain genetic traits. Some of these are associated with diseases, like cancer, while others are for much more benign conditions, such as whether you have detached earlobes or why [Brother] thinks cilantro tastes awful.
At the moment, 23andMe is probably the most-recognized consumer genetic testing company. They claim to have some 30,000 customers, and some of them have already made their information publicly available. (If you are interested in seeing examples of this you could go meet Geoffrey and his genes or go look at this graphically-unfriendly list of public genomes.)
At the moment all I’d be receiving and publishing is data from 23andMe. But I think it’s probable that in the next few years I’ll have the opportunity to publish my entire genome so, for our purposes, that’s really what I’ll focus on from here on out.
II Why does this affect you? (Part I: Genetics)
We’re related? Are you sure? Because of your relationship to me, I share approximately 50% of my genes with each of you (but I want them back!). To put it simply, what this means is that any genetic information revealed about me will say something about you. But what?
In almost every case, what my genetic information says about me will be a probability (for example: genetic variant X is thought to contribute to an 18% increase in lifetime risk of developing diabetes). And, in almost every case, what it says about you will be even more probabilistic (because you are my parent/sibling, you have a 50% chance of having a genetic variant X that is thought to contribute to an 18% increase in lifetime risk of developing diabetes).
Most genetic information is probabilistic for several reasons, including the fact that many genetic factors remain unidentified or poorly understood. Even more important is the fact that most traits, whether diseases or other characteristics, such as height or high IQ, are influenced by a complex combination of genetics and environment. That means that, most of the time, no matter how much you know about an individual’s genes you won’t be able to predict what traits they will develop with anything resembling certainty.
Huntington’s (and other scary genes). Of course, there are exceptions to everything I just said. For instance, it is possible that I could learn something in the future that would also tell me something about one or more of you with much more certainty.
Here’s probably the most extreme example (although it’s also extremely unlikely): I find out that I am homozygous for Huntington’s Disease, which is a dominant monogenic degenerative condition. How about we try that in plain English? Huntington’s Disease is a disease where, as you age, the nerve cells in your brain deteriorate. It’s a truly terrible disease to suffer from and it’s caused by a mutation in a single gene (that’s what “monogenic” means). If you have even one copy of that gene you have a 100% chance of developing the disease if you live long enough (that’s what “dominant” means).
So, if I had my genome sequenced and found out that I had one copy of the Huntington’s gene, what would that mean? First, it would mean that I would develop Huntington’s at some point (symptoms usually start in middle age) unless I either died of other causes or unless a cure was developed. It would also mean that each of you had a 50% chance of possessing the Huntington’s gene as well.
Now let’s say that I somehow wound up with two copies of the Huntington’s gene, which can happen in rare cases. That means that I received one copy from mom and another from dad, which means that both mom and dad would be Huntington’s carriers. At your age you should expect to see symptoms soon, if you weren’t seeing them already. (Of course, the fact that neither of you have the symptoms of Huntington’s is a very, very good indicator that you’re not carriers, but this is a hypothetical.) It also means that, [Sister] and [Brother], your chance of developing Huntington’s would be at least 75%. That’s something that you might not want to know if there’s nothing you can do about it. Then again, you might want to know so you can be on the lookout for symptoms and plan for the disease in advance.
Why spend so much time talking about Huntington’s Disease? Because, in many respects, Huntington’s is a worst case scenario. It is determined entirely by your genes, it is fatal and, for now, it is incurable. And when thinking about risks it’s important to try to understand the worst case scenarios.
Then again, it’s also important to remember that Huntington’s is not typical. Even other scary diseases that we think about (including Alzheimer’s, heart disease, cancers, etc.) lack at least one of the features that makes Huntington’s so frightening. Alzheimer’s, for instance, is not deterministic in the same way that Huntington’s is. Even if you have the worst combination of Alzheimer’s genes, there is still a reasonable chance that you will never develop the disease at all.
Ultimately, it’s important to keep in mind that the vast majority of what I’ll learn about myself by sequencing my genome is likely to be benign and/or uncertain. And because we each share only 50% of that genetic information, anything that you learn about yourself is almost certain to be even less certain. But there are exceptions, and I hope that I’ve given you a sense for those as well.
III Why does this affect you? (Part II: Discrimination and Other Risks)
Of course, even if I publish my entire genome for the world to see, that doesn’t mean that you need to be one of the people looking. In some ways this is no different than what would happen if, for example, mom went and had a genetic test for certain breast cancer genes because our family has a history of breast cancer and her doctor decided it was a good idea for mom to be tested. She’d find out her results and then we’d all have to decide how to share and discuss that information within the family.
The big difference here is that, by publishing my genetic information online, it’s possible for other people to access that information and to use it in ways that you might not like. That could include telling you about what my information says (or what they think it says), and what that implies for you and your own genetic information.
There are other potential risks to consider as well. This could include your being subjected to negative or upsetting comments or attention from friends, colleagues or even complete strangers (“Dan has bad gene X. He sucks!” or “your brother/son has bad gene X. You suck!”) or simply having to spend your time answering questions about my or your genes (“How do you feel about the fact that Dan has bad gene X?”). It’s also possible that somebody could trace my ancestry – and thus yours as well – back to some infamous historical figures (like Genghis Khan, although that might not be much of a surprise).
Genetic Discrimination. One particular risk that people tend to worry over is genetic discrimination: the possibility that somebody could use genetic information to deny you some type of benefit or opportunity. A few words about this: it is now illegal for employers or healthcare insurers to discriminate against you, me or anybody on the basis of our genetic information. That’s a recent legal development and a very good thing. However, it’s not perfect protection. Genetic discrimination will always pose at least some risk for several reasons. First, just because something is illegal there’s no guarantee that somebody won’t break the law and, what’s more, there’s no guarantee that they’ll be caught or stopped if they do.
Also, the new federal law that prohibits genetic discrimination (it’s called the Genetic Information Nondiscrimination Act, or GINA) doesn’t cover every kind of insurance. For instance, disability insurance and long-term care insurance (which is something you might want if, for instance, you found out you carried – or might carry – the gene for Huntington’s) are not covered by GINA, although discrimination on the basis of genetic information may still be illegal under other federal or state laws. As a practical matter, however, the risk of discrimination to any of you is much lower than the risk is to me. And from all estimates (as well is in my opinion), the risk to me is very small to begin with.
Unknown Risks. It’s difficult to say with any confidence how likely it is that any of these risks will materialize. What’s more, it’s my opinion that the most important category of risk in all of this is what we can think of as “unknown risks.” Here is how the PGP’s informed consent form (which I helped write) puts this problem:
Your DNA sequence data, trait data and other information related to you that is made publicly available by the PGP, while directly associated only with you, may also have relevance to your family members. Although in many instances any conclusions that may be inferred from your publicly available information may be speculative with respect to you, and even less predictive with respect to your family members, the complete set and magnitude of the risks that the public availability of this information poses to you and your relatives is not known at this time. You are strongly encouraged to discuss this study and its potential risks with your immediate family members. (emphasis added)
The act of publishing identifiable genetic information for public consumption is still a new exercise. Although I certainly wouldn’t be the first to undertake this, there also aren’t many public genomes or even partial genomes out there at this point. (The number is probably fewer than 100 worldwide, although it’s hard to say for sure.) In the end, this is all so new that the long-term consequences of making genetic information publicly available are not well understood at this point.
As a result, there’s simply no way for any of us to list or evaluate all of the risks associated with this decision. Just as with every decision in life, we need to do the best that we can with the available information.
(One final aside is that the risks associated with this decision aren’t necessarily limited to the four of you. One important issue that I didn’t mention above is the possibility that I will be placing my future children at risk. Although I don’t have any yet, I still need to consider the fact that this decision could have consequences for my children – if they are biological they’ll share the same 50% of my genes that you do – who will not have an opportunity to provide any of their own input.)
Why am I doing this?
So why am I even considering doing something that poses risks – both known and unknown – to me and the members of my family, both present and future?
At a very pragmatic level, having now spent years thinking and writing about the risks and rewards associated with public genomics research, I have come to conclude that the rewards simply outweigh the risks. I actually think this is true by a wide margin. But that’s just my own educated guess and, even if that is true in the abstract, it’s always possible that one of us could wind up as an exception, harmed by this decision in any one of the ways described above.
More fundamentally, I am willing to assume the risks of participation – and I am asking you to assume a share of those risks as well – because I believe in the importance of scientific research to societal progress. And I believe that neither can succeed without some degree of sacrifice and risk-taking by people like me. I am not a scientist, but I am fortunate to have the opportunity to participate in important scientific and societal research that, although it may not benefit any of us directly, has the long-term potential to improve the lives of many.
There are countless people and professions – from the Marine Corps to the Peace Corps, and so many individuals and occupations in between – that undertake great personal risk in an attempt to improve the world around them. It is abundantly clear to me that the risks of participating in Genomes Unzipped, the Personal Genome Project or other similar projects are trivial by comparison.
But because the risks extend to you as well, I believe that the decision to move forward is one that I should not make alone. Before I wrap this up I want to share with you a few words from Jason Bobe, one of the driving forces behind the PGP and a close collaborator and friend, which I find particularly inspiring.
These individuals are the astronauts of our era. By sharing their genomes and phenomes and making them broadly available through participation in public genomics research studies like the Personal Genome Project (PGP), these pioneers will radically accelerate our ability to explore new frontiers of human knowledge. In doing so, they face potential risks. They are putting it on the line for our benefit and for the benefit of future generations. They deserve our support. To the moon!
All of you have supported me in so many ways throughout my life, and I would not have this opportunity were it not for that. I hope that I will have your support in this decision as well.
See you in a few days!