Would you want to know the secrets of your own genome, perhaps discovering that you are at risk for a disease like Alzheimer’s, for which there is no cure? If you did find out what lies in your genes, would you ever decide to make that very private information public?
Duke University geneticist Misha Angrist decided to do both, becoming part of the Personal Genome Project (PGP), which was launched in 2006 in the hopes of helping scientists better understand the impact of genetics and advance the field of personalized medicine. The PGP aims to publishthe genomes, medical histories and other information about its participants; project leaders hope to recruit 100,000 volunteers in all.
Angrist wrote an intriguing in-depth look at the project and his experience called Here Is A Human Being (Harper, Nov. 2010).
Why did you decide to make your genome public and write this book?
Once I learned about the Personal Genome Project, I was already convinced this would be a great opportunity to portray genetic and genomic information in a different light. I started going up to Boston and badgering George Church [the Harvard geneticist who helped lead the Human Genome Project before starting the PGP] to let me in. I thought it would be much more interesting to write it from the inside and see if I was prepared [to deal with the information and make it public].
Were you afraid to learn about things like your risk for Alzheimer’s disease, which medicine really can’t do anything about?
I had moments of pause. … When I first [learned about some of my genes] in 2008, I didn’t have a genetic counselor or even the customer-focused software that companies [now selling genome scans] have. I just had a list of genotypes. I saw all of these risk alleles for multiple sclerosis and I got a little freaked out. That was my first encounter with my own genetic information. I had insisted that I wanted to do it alone and I was anxious for a day or two, until I started digging into the literature.
In your book, you write about researcher Robert Green’s counterintuitive findings about how some people handle potentially devastating genetic information.
These were first-degree relatives of Alzheimer’s patients. They were already at greater risk. They opted to be in the study knowing that they might learn [they had the gene]. [Green found that] for people who want to know, they can be told with very little chance of any sort of long-term psychological damage.
Many people say they would kill themselves if they found out.
I suppose that’s possible.But for those who want to know, is anxiety the only thing they can get from that information? The answer is no. They can make plans about how they want to live given a statistically high risk of developing Alzheimer’s. They can also avail themselves of clinical trials, which will almost certainly be more helpful to them while they are still asymptomatic, if they are going to be helpful at all.
Nobel Laureate James Watson had his genome sequenced and made public. He asked not to know about the Alzheimer’s gene (APOE), but someone figured it out from what he did publish. How?
In genetics there’s a phenomenon called linkage disequilibrium. Unless we’re identical twins, we’re all unique a mosaic of Mom and Dad. Chromosomes are inherited in pairs; [during reproduction] they attach and crossover and shuffle their components.
That said, large chunks of chromosomes are inherited together and get passed down through generations and they do this in a way such that if you line up a bunch of chromosome 7’s from a dozen people or 1,000 people, you get a sense of what blocks tend to travel together. To avoid [revealing Watson's] APOE genotype, the group scrubbed some data on either side. It’s like if you have a photograph of something you’re selling on Craigslist and don’t want to disclose the serial number, so you retouch it.
They didn’t remove enough data. The linkage disequilibrium block was big enough that [another scientist] could infer what his genotype was likely to be.
You had a strange coincidence in your own family: in your previous work, you studied the genes for Hirschsprung’s Disease. Then your nephew developed the rare condition, which causes bowel problems when certain nerves don’t develop in the gut.
When that happened, I was really shaken. [My brother joked], “Why couldn’t you have worked on the gene for large penises?” We were all thinking the same thing. My brothers and I are not people of deep abiding religious faith. I’m agnostic. But when something like that happens, where somehow I’m in the lab for eight years working on a disease that affects 1 in 5,000 newborns and then my brother’s second son turns out to be one of those in numerator, I was shaken and flabbergasted. It seems like one of those events that is for me difficult to just write off as a random thing. But of course, that’s a solipsistic way of looking at the universe.
How can companies like 23andme sequence your genome for $199, but if you undergo tests for just a few genes in a doctor’s office, it costs you thousands of dollars?
The new economies of genetic technology have not penetrated the clinic. Myriad Genetics still charges $3,100 to test for two breast-cancer susceptibility genes.
Companies like 23andme type about a million markers. What that means is that if you think of the genome as highway, having the whole thing done is like getting all of the white lines. They’re basically giving you mile markers.
So could you find out about breast-cancer genes much more cheaply from these mail-order tests?
Initially, those companies shied away from [giving information about] carrier-status genes [like those for breast cancer]. I think that’s because those are things that were seen as the bailiwick of conventional medical genetics and they implied reproductive risk. They opted for lower-impact sorts of traits like [the gene that makes] pee smell funny after asparagus or arthritis genes.
What they learned then was that people actually wanted useful information. People contemplating having kids would like to know what Mendelian risks they carry. So 23andme now includes genes for 25 conditions like sickle-cell anemia, Tay-Sachs and [the breast-cancer genes] BRCA1 and 2.
Did you feel you were putting yourself at risk for other consequences by making your genome public?
The Personal Genome Project consent form is long and scary. It includes things like “This may reveal non-paternity” [i.e., your father might not be your real dad] and some more fanciful things like “Your DNA could be planted at a crime scene and you could be cloned.”
One risk is that you could be discriminated against for life insurance and that sort of thing. The Genetic Information Nondiscrimination Act (GINA) was passed in 2008, but not everyone even thinks it was good idea or even necessary — it has lots of loopholes. It protects against genetic discrimination in health insurance and employment, so if you carry a mutation that makes you likely to become a drug addict, they can’t fire you. But it doesn’t include life insurance or long-term care insurance.
So what would you say to people who are considering having their genomes sequenced?
This is not for everybody. I don’t think there should be any expectations that this is going to be obligatory. I do think within 10 years we’re going to be getting whole genomes from newborns but my hope is that we will find ways to use that information responsibly and in ways that will maximize health and have less to do with ancestry or forensics.
I would say, What are your expectations? What do you hope to get out of this? If you think this going to be integral to your health or happiness or sense of identity, you might be disappointed. The most compelling reason for me to do it was simply curiosity about genes, the genome and genetic information and how it all works, as opposed to understanding at the most personal level.