Elements

The F.D.A. vs. Personal Genetic Testing

By David Dobbs November 27, 2013

The United States Food and Drug Administration is not known for its prose. So
the warning letter that it sent to 23andMe, the direct-to-consumer genetic-testing
company, on November 22nd, was a surprise in more ways than one. It reads like
the letter of a jilted lover, Misha Angrist, a former genetic counsellor who writes
about personal genomics and teaches at Duke University, said. We went on
fourteen dates! We exchanged all these e-mails! We held hands in the park! Now
youre telling me, Fuck you, and kicking me to the curb.

The letter was sent to the 23andMe co-founder and C.E.O. Anne Wojcicki after
the breakdown of negotiations about how to regulate the companys delivery of
genetic health-risk information. Since July of 2009, the F.D.A. writes, the agencys
Oce of In Vitro Diagnostics and Radiological Health had worked patiently with
23andMe, sharing more than 14 face-to-face and teleconference meetings,
hundreds of email exchanges, and dozens of written communications. Then the
company had not only failed to coperate with the agency but had completely
ignored it for six months. After listing everything that theyd talked about, and all of
the ways in which the company had rebued its entreaties, the F.D.A. ordered
23andMe to stop selling its ninety-nine-dollar DNA tests, which the agency says
constitute medical advice and therefore require F.D.A. approval. If 23andMe didnt
cease selling the test and resume negotiations, the F.D.A. said, it would take
corrective actions that might include, but are not limited to, seizure, injunction, and
civil money penalties.

As of Wednesday morning, ve days later, the company is still selling its spit kits:
you can mail your saliva to the company and have it analyzed for information about
your personal genome, from your caeine sensitivity to your maternal haplogroup.
The companys Web site continues to showcase a story about how a simple DNA
test led to an unexpected diagnosis for a mother and daughter, changing their lives
foreverprecisely the kind of marketing that the F.D.A. has objected to. Initially,
the companys only public response to the F.D.A.s letter was three sentences of
boilerplate. On Tuesday night, Wojcicki wrote a short blog post, acknowledging,
We are behind schedule with our responses to the F.D.A. The company then
began to e-mail customers. While the e-mail largely re-states Wojcickis blog post, it
also apologizes for the limited response to the questions many of you have raised
regarding the letter and its implications for the service, and warns, We dont have
the answers to all of those questions yet.

Many people who have tracked the rise of whats known as direct-to-consumer
(D.T.C.), or personal genetic testing, have been expecting a con ict between a
company in the eld and the F.D.A. since at least 2010, when the agency rst
announced that it considered the spit kits medical devices and consumer genetic-
testing services medical interventions, which require regulation. Advocates for easy
access to personal genetic information feared that the F.D.A., and the medical
establishment vis--vis the agency, would use this regulation to gain tight control of
genetic datawhich has become increasingly sought after, for both medical and
personal reasons. Those who advocate D.T.C. genetic testing, even as they fume at
23andMe for letting things go so sour with the F.D.A., suspect that theyre now
watching a government power grab.

Aggravating the con ict is a cultural clash between Silicon Valley, with its devotion
to libertarianism and self-knowledge, and a ponderous old-school bureaucracy. But
as the veteran journalist and F.D.A. watchdog Matthew Herper notes in one of the
sharpest pieces written on this debacle, the agencys investment into at least four
years of negotiations suggests that it was trying to be accommodating. Herper
reluctantly concluded that 23andMe is either deliberately trying to force a battle
with the F.D.A., which I think would potentially win points for the movement the
company represents but kill the company itself, or it is simply guilty of the single
dumbest regulatory strategy I have seen in 13 years of covering the F.D.A.

Nearly everyone remains mysti ed that 23andMe stopped communicating with the
F.D.A., even as the company launched new marketing campaigns and claims. One
theory is that the company, convinced that the F.D.A. is incompetent, is trying to
provoke agency to overreach so it can then outmaneuver it. Herper told me that he
thinks this would be foolish, given that he has never seen the F.D.A. overreach, and
that it is not an agency to tri e with. As the genomics researcher and blogger known
as Mike the Mad Biologist put it, the F.D.A. is like those humongous tractors used
to move space rockets: theyre slow, but crush everything in their path.

Another possibility is that the company simply dropped the ball. Linda Avey, who
founded 23andMe with Anne Wojcicki, in 2006, and left in 2009, still owns shares
and keeps in touch with some employees, says she doesnt know what created the rift
between the company and the F.D.A. It surprised me, she said. But she pointed
out that 23andMes general counsel, whom she understands was leading the
negotiations with F.D.A., left the company this summer; perhaps it fell through the
cracks.

The whole time I was there, Avey told me on the phone yesterday, we were in an
outreach mode with the F.D.A. I cant imagine there was that much of a cultural
shift since then. It might be they werent paying close attention. She admits this
sounds strange, but thinks that it is no stranger than any other explanation.

At the center of this dispute is the F.D.A.s designation of the spit kit and 23andMe
service as a medical device. In its letter, the F.D.A. seems to argue that its not the
actual DNA genotyping microarray (the physical instrument 23andMe uses to
perform its genotyping service) that it sees as the medical device but, rather, the
combination of the assay and the companys oer to tell customers what the assay
means. The raw data from the microarray is a bunch of lettersGs, Ts, Cs, and
Asthat to most people mean nothing. 23andMe takes that data, identi es the
gene variants that it represents, and, by drawing on the scienti c literature and on its
own database, tells the customer about the assays medical implications. A 23andMe
report might tell you that you carry, say, a gene variant that slightly elevates your risk
of heart disease, another that protects you from celiac disease (if you have digestive
problems, they probably stem from something else), or, in one of the companys
most laden tests, that you have either zero, one, or two copies of a gene variant that
increases the risk for Alzheimers, and thus stand either a low, a modest, or a
shockingly high chance of developing Alzheimers. The company delivers this news
with material about how solid the associations are, links to the literature that theyre
based on, links to a video series on how genetics work, and many, many caveats.

To 23andMe and to most of its customers, this is information that a person has
every right to know. To the F.D.A., it is medical advice, which makes 23andMes
delivery system a medical device. The F.D.A.s letter speci cally mentioned
companys inclusion of some risk variants of the so-called breast-cancer genes
BRCA1 and BRCA2 as the sort of high-consequence information that might lead
people to take radical medical action without adequate medical advice. What
surgeon would do a mastectomy based on a 23andMe result? A reasonable answer
seems to be noneuntil you remember that surgeons already do thousands of
unnecessary operations every year, and that if you cant nd a willing surgeon here
you can always go abroad.

Yet 23andMe delivers this information with little friction or guaranteed guidance.
Kenneth Britten, a neurobiologist and a customer, learned he has one copy of the
gene that increases Alzheimers risk, which raises his nominal risk to about one in
seven. But he then did enough reading to learn that because neither of his parents
developed Alzheimers, he could essentially erase this extra nominal risk if he started
exercising regularly before he developed symptoms. (He says he now works out a
lot.) But hes a neurobiologist in his prime. A fty- ve-year-old who is confused
and depressed and learns that he carries two copies of the risk gene and stands an
eighty-per-cent chance of getting Alzheimers might reach for a gun, which is the
kind of scenario that some genetic counsellors worry about.

My own 23andMe assay included the same Alzheimers result that Kenneth
Brittens did. I, too, learned, rather suddenly, that I carry one copy of the risk gene
and thus have a nominal Alzheimers risk of around thirteen per cent. That news
was given to me after I read a special, extra contextualizing statement that 23andMe
attaches to such resultswhich took less than a minuteand clicking on a small
square on my pro le. Out popped little Pandora, provoking four quick reactions:
rst, a cold fearful shock; second, a rapid recognition, as my brain churned to
contextualize this ugly surprise, that family history and personal health probably cut
my tripled risk in half; third, a feeling of intense relief that I did not have two copies
of the risk gene; and, nally, the thought, as I walked around the room letting my
pulse drop, that it was hard to imagine that anyone could resist clicking that little
square.

How do we provide the necessary counsel to people opening Pandoras box without
eectively locking it? The F.D.A. has a point: genetic-risk information needs to be
reasonably solid, and its recipients need to be properly served; theres a place for
selective paternalism in genetic testing. Yet the agency seems like a poor candidate
to strike this balance. The hope is that it will demand documentation con rming
23andMes method for the most laden results, and that it will require a better lter
one thats thinner than a doctors visit but thicker than a click.
If the F.D.A. indeed insists on making 23andMe prove beyond doubt the validity of
every single correlation, no genetic-testing service will be able to economically
deliver medically relevant genetic information directly to consumers. It will destroy
the industry and leave medical genetics in the hands of a medical establishment that
has already failed to give people an easy way to obtain and use the elemental
information in their own spit. Even now, many doctors who want medically relevant
genetic information about a patient get that information by asking her to sign up
with 23andMe. Meanwhile, this companys cheap, widespread testing, which has
gathered genetic, ancestry, and health data from nearly ve hundred thousand
people, has created a rich medical source of risk information.

If the agency instead forbids the company from interpreting the teststhat is, if
the agency insists that the companies strip from the raw report of genotypes any
information about health risksit would, as the Cold Spring Harbor geneticist
Gholson Lyon pointed out this week, threaten to make the data meaningless.
Stopping 23andMe, writes Lyon, is not improving medicine. It is delaying, or worse
stopping, the revolution that todays medicine desperately needs. If that happens,
Lyon writes, were stuck with a slow, closed system whose constrictions prevent
genetic information from helping even those who provide it. Two years ago, Lyon
writes, he used genetic testing to identify the cause of Ogden Syndrome, a rare, fatal
disease that killed a four-month-old child named Max. But the rules and
regulations for genetic testing in the U.S. meant I could not share the results of
the familys genetic tests with them.

The family laid Max to rest without knowing of the gene that killed him. When one
of the familys sisters became pregnant and asked Lyon what he knew, the rules
forbade him from telling her. Under the rules of the system that 23andMe is hoping
to replace, she would have to set about having any other children without knowing
that her family carried a potentially fatal genetic combination that, if it were not
tested for, could kill again.

David Dobbs is the author of the best-selling Atavist story My Mothers Lover, and writes
features and essays for a number of publications.

Photograph: Michael Rosenfeld/picture-alliance/dpa/AP.

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