Neurogeneticists Divided Over Gene Screening Sites for Public

ARTICLE IN BRIEF

Neurogeneticists are grappling with the promise and the pitfalls of initiatives like 23andMe and other online efforts that aggregate genetic data as well as phenotypic and other epidemiological information about people with neurologic illnesses.

In March, the personal genetics site www.23andMe.com announced a new Parkinson disease (PD) initiative, in collaboration with the Michael J. Fox Foundation and the Parkinson's Institute. First launched in 2007 with the goal of demystifying personal genetics, 23andMe offers individual genotyping for $399: you order a kit online, spit into a tube, and send back the sample for lab analysis of everything from your genetic risk for type II diabetes to your Mendelian earwax type (not really).

The PD initiative takes this one step further, aiming to enroll 10,000 people with PD in the 23andMe Personal Genome Service™. They'll get at the bargain price of $25 - underwritten largely by a major donation from Google founder (and husband of 23andMe co-founder Anne Wojcicki) Sergey Brin, who announced last September in a personal blog that he has the LRRK2 G2019S mutation, which confers a 20- to-80-percent added risk of developing PD.

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Researchers will combine the genetic data with phenotypic information submitted by participants, as well as data from existing 23andMe clients who will participate as healthy controls, to create a massive searchable database that they hope will accelerate discovery.

WARINESS AND EXCITEMENT

The announcement was greeted with both excitement and wariness from the neurogenetics community. At the AAN annual meeting in Seattle in April, a short discussion session about the initiative exploded into debate that many participants report could have continued for hours longer than the allotted 15 minutes.

Neurogeneticists are grappling with the promise and the pitfalls of initiatives like this one, and other online efforts to aggregate genetic data as well as phenotypic and other epidemiological information about people with neurologic illnesses.

Among the advantages: Online data-gathering allows initiatives like 23andMe's to reach out to people who might be far away from academic medical centers and unlikely to participate in traditional, clinics-and-mortar trials. With accrual a perpetual problem for neurologic research as in any field, the ability to access a larger population could sharply up the pace of progress.

Meanwhile, patients can enter clinical trials that might otherwise be closed off to them, gain access to their genetic information (at a bargain price), and connect online with other people who have similar conditions or risk factors - a Facebook-age version of traditional support groups.

But the initiative also presents challenging questions; among them: How do you do genetic counseling over the Internet?

On 23andMe, when you get to actually ordering a kit and get the consent form, they run through concerns like 'You may learn what you aren't anticipating and cannot control, and that may cause you psychological distress.' They say there may be a lab error. They say 'Don't change your health behavior because of this.' They explain that 'the information may not apply to you because of your ethnicity.' All this comes at you quickly at the same time you're buying a kit, said Jill Goldman, a certified genetic counselor at the Sergievsky Center of the Taub Institute and the Center for Parkinson's Disease and Other Movement Disorders at Columbia University Medical Center.

Figure. DR. WILLIAM ...

That's information that genetic counselors spend at least an hour discussing with patients in person. There's not enough warning about the potential negative effects of testing, or the limitations, said Goldman. With release forms online, people tend to just sign those things when they think they want something. There's really no discussion of the risks of genetic testing in general, how to discuss testing with your family, and whether or not they want you to share that information on the Internet. These are family situations.

Goldman also noted that although professional guidelines recommend not testing children under the age of 18 for an adult-onset condition, nothing on 23andMe discusses pediatric testing, except to state that one must be an adult to send in results and that kits are not meant for children under three because of the quality of the information.

Another thing that's very concerning, she said, is that the consent section notes that if you share this information with your doctor, it could become part of your medical record. That implies that maybe you shouldn't share it with your doctor, and if it's going to affect your health, that's the one person who should know.

A PD RESOURCE

William Langston, MD, president of the Parkinson's Institute in Sunnyvale, CA, and an advisor to the 23andMe initiative, said that his views on the issue have evolved within the past year. Where I got comfortable with this project is that it's just for people with Parkinson disease, he said. You're not informing someone about their risk for developing Parkinson disease - they already have it. We're informing them about a likely cause of their disease, which we do all the time. Anecdotally, it's been suggested that this may cause people to start worrying about their own kids and what to tell them, but I think kids today are just much more comfortable with this kind of information.

Dr. Langston himself has done 23andMe's genome screen, as has his son. He admits that the broader 23andMe platform, beyond the Parkinson study, poses some worries to him. For example, three of the BRCA genes are on 23andMe. Would you want to find out on your own that you had one of those mutations, with no help? I just looked for my own to see if I had it, and all it asked me was, 'Do you really want to know this?' There was no counseling.

But he noted that there seems to be a contrast between how people seek genetic information in the doctor's office and how they do it online. No one asks us for the ApoEe4 test, the Alzheimer gene. Why would you want that information if there's nothing you can do about it? he said. But at 23andMe, the most common question they get from people who sign up is 'Can I get the Alzheimer's test?' It is not currently offered. There's either something different about the generation that does this, or not being in the doctor's office.

Dr. Langston compares the furor over personal genetic testing to the response to the introduction of home pregnancy tests. There was a hue and cry in the medical community over that, he said. It was thought that women alone shouldn't be entrusted with that information - what if someone wasn't prepared and committed suicide because she didn't want to be pregnant? Doctors should be involved!

It's not quite the same thing, countered Corrie Smith, a certified genetic counselor at the University of Washington departments of neurology and medical genetics. Pregnancy is a transient state. It's not something that was there from the moment you were conceived and will be with you until you die. Your genes are something that can't be changed within yourself, she said. That said, I do agree that as genetic testing becomes more commonplace, people will get used to the idea that 'Of course, I know my carrier status for this list of diseases, or have had genetic testing to find out how I metabolize certain medications.'

ATTITUDE SURVEY

Smith, although skeptical of what she calls recreational genetics, praised the 23and Me/Parkinson's Institute/Fox Foundation partnership for its plan to survey patients who get tested on their reaction to learning their results and how it may have affected their lives. That's important, she said. I'm still not sure I agree with the approach, but if they're going to do it, it's important to try to figure out if it's causing psychological harm, changing what people do, changing how they treat their children. That's the only way we're going to know if these things are harmful.

Exactly, said Dr. Langston. We all have anecdotes about the impact of this on patients, but that's not science. A really well-done survey of people who have just learned their status could benefit all of us.

Privacy is another concern raised about sites like 23andMe, as well as Patients Like Me, a sort of Facebook for people with serious or chronic health conditions, where they share everything from what medications they're on to their weight and level of disability - in a searchable system. Some doctors and genetic counselors are worried not just about privacy of the users - who have made their own decisions about what information to share - but also that of their families. (Indeed, Patients Like Me doesn't have the traditional online privacy policy- it has an openness policy.)

If you're sharing information about a disease that has a heritable component, this is not just your information, it's your entire family's information, said Wendy Chung, MD, PhD, director of the clinical genetics program at Columbia University Medical Center. People on Patients Like Me have posted faces, first names, and unique identifiers - people can figure out who they are. What if you're an employer who realizes you're interviewing the brother of a man with heritable ALS? Maybe if you have two equal candidates, you won't take this one.

Families with genetic diseases have already grappled with these issues, said Jamie Heywood, a co-founder of Patients Like Me, which also promotes research and has launched a genetic search engine (www.patientslikeme.com/als/patients/find) on known familial ALS genes.

I know literally dozens of families with genetic ALS, many of whom are my close friends. They understand this issue, they communicate about it, and they make strategic decisions, Heywood said. In some families, certain people are active and tested, and others don't want to get tested or talk or think about it. Do they object to their family members' openness? Yes, some of them do, but do we want to live in a world where we restrict one person from revealing their information because it will affect someone else? How do you live in a society where you restrict someone's ability to communicate information about themselves?

Figure. CORRIE SMITH...

Heywood argues that privacy objections to projects like the Patients Like Me genetic search engine substitute theoretical harm for real harm. If we assume that someday ALS will be effectively treated, with something like insulin or Gleevec [imatinib mesylate], and you're remotely realistic about the impact of things like privacy constraints on the cost and difficulty of implementing research, there isn't anyone who will say it delays you by less than a year. It adds up to death by a thousand paper cuts. One year's delay means that 5,000 people will die.

He acknowledged that, in the history of ALS, there has been harm from trials gone wrong (as with virtually any condition). There were drugs on which people did worse rather than better. There were privacy abuses. There were patients who felt that things didn't go right. But when I weigh 5,000 guaranteed deaths a year against these few cases of harm, I can't think of a single patient who believes we're balancing this equation in the right way.

Indeed, he argues, significant numbers of ALS and Parkinson disease patients have gone off the grid, believing the conventional research model is not serving them, and are pursuing treatment options that can result in even more serious abuses. There are clinics in the Ukraine that will give stem cell transplants, charlatans who will provide chelation therapy and all sorts of things that should never be done and are often harmful.

But although Patients Like Me and 23andMe take a similar online approach to personal genetics, Heywood isn't rushing the genetic information component of his site. Patients Like Me is, at its heart, a personalized medicine platform. If you want to know what 42-year-old males take for depression when they have anxiety and depression combined, and find out if they're happy with that solution, you can answer that question on our site right now, he said. We want to introduce meaningful genetics into this platform - that's a meaningful variation in your phenotype that can inform your ability to make treatment decisions. That's why we started with the ALS database. If you have an SOD1 mutation, you are a different patient with a different outcome than the average sporadic ALS patient.

We want to know what are the most important variables in managing your disease: your comorbidities, your symptoms, your environment, the medications you're taking, he continued. As genetics becomes important, we add that in. In the case of ALS, we can provide variations in your prospective outcome based on what mutation you have, and that information belongs to patients.

That's a fair point, said Dr. Chung. If at this point we had a cure for this form of ALS, it would be difficult to round up all these patients right away. In that sense, registries like this are necessary.

But she, and many others in the neurogenetics community, would still like to see the already-open Pandora's box of online genetics have, at minimum, a few more safeguards.

If it were made more obvious to them what the potential down sides could be, that would be better, Dr. Chung said. I don't want to see the effort squelched, but I do want there to be a way to be a little more in people's faces when they sign up for things like this, knowing what they're letting themselves in for and what they are and are not giving away. It's our obligation as a research community to offer options and let patients be advocates for themselves. This is a powerful and exciting way to do that, but it may have unintended consequences.

NEUROLOGY TODAY WINS AWARDS

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Neurology Today received top honors for editorial excellence in May in a national competition by the American Society of Healthcare Publication Editors, a nonprofit trade organization of health care journalists and editors.

The medico-legal column, Legal-Ease, earned a gold award in the category of Regular Column: Contributed, and the newspaper was awarded a silver medal in the category as Best Custom Publication.

The award-winning Legal-Ease articles by medical journalist Gina Shaw featured a controversial insurance company program that offered physicians financial incentives to switch to generic drugs (Physicians Rewarded With $ to Switch to Generics, April 3, 2008); the legal liability neurologists face when their patients drive (When Your Patients Drive on Meds, What is Your Liability Risk?, April 17, 2008); and a Supreme Court case affecting drug injury lawsuits (Suing Drugmakers in State Court: Will Supreme Court Case Settle Pre-Emption Question?, Dec. 4, 2008).

To read the award-winning entries, visit www.neurotodayonline.com.