DTC genetic testing: Caveat Emptor

I met Cynthia in a van from the airport, headed to the annual meeting of Family Tree DNA (familytreedna.com), where I was to speak about genetic testing. A beautiful blonde who looked decades younger than her 60 years, she’d led a painful life, with type 1 diabetes since childhood, just like her father, brother, and grandfather. The family, so they thought, was 100% European, mostly Polish.

My talk did not go over well. Genetic testing companies and their customers do not like to hear that a geneticist thinks their tests should be regulated, for reasons of both privacy and accuracy.

Cynthia, intrigued despite my warnings, sent off a spit sample to 23andme (23andme.com), to learn about her ancestry. She got that, and more – health information, including a “lower than average” risk of developing diabetes. deCODE Genetics (http://www.decodeme.com/) gave her the same answer. Ditto her brother.

But her brother’s Y chromosome held an explanation. About 1200 years ago, a Korean man and at least two Chinese men dropped a bit of DNA into the family. So when Cynthia went back to 23andme and recalculated, entering “Asian” instead of “European,” her diabetes risk shot up to 90%.

So it looks like ancestry testing helped get this family on the right track. But another way to look at it is that the health-related tests are simply not precise enough.

This past week “direct-to-consumer” genetic testing took a hit, and it’s about time. First the Walgreen’s near-fiasco of off-the-shelf direct-to-consumer genetic tests, then a white paper from the American Society of Human Genetics calling for oversight of ancestry testing.    To top that off, I got a call from a writer for a popular psychology magazine asking me for a “sound bite.” A sound bite? Genetic testing isn’t quite that simple.

Genetic tests for well-studied mutations, delivered by a genetic counselor or physician, in person, are fine. But the genetic “associations” gleaned from population data, although useful in research, often cannot reveal much of anything about an individual – such as Cynthia.

Caveat emptor. 

[cross-posted from Ricki Lewis' blog, GeneticsWatch.]

"Cancer-free" baby born in UK: what's wrong with this picture?

So: today's news reports that the first "cancer-free" baby has been born.

"What's this?" you ask. "Isn't it awfully rare for babies to have cancer?" Yep. Especially breast cancer, which is more common in older women. But the genetic test to identify known breast-cancer-causing mutations has been around for some time. Now, for the first time, it has been used as a prenatal test--technically, in this case, through preimplantation genetic diagnosis (PGD), which is testing embryos conceived through IVF prior to their being implanted in the uterus.

Certain rare BRCA mutations greatly increase a woman's risk of breast cancer and ovarian cancer--so much so that some women with these mutations decide on prophylactic surgery to remove their breasts and ovaries. However, because these really bad mutations are rare, experts recommend that only women with a strong family history of breast cancer pursue testing. The news story doesn't say whether the couple had such concerns, though presumably this is the case.

Stories like this one don't help the general public understand what genetic testing can and can't do. Even BRCA results are probabilistic: not everyone who has a positive result will go on to develop breast cancer. And there are prophylactic and curative treatments available for breast cancer (though they are, obviously, pretty awful). And who knows what the state of medicine and oncology will be by the time the BRCA mutation carrier born today is old enough to worry about breast cancer?

The opposite set of concerns plays in here too; the fact that this fetus happens not to have any of the mutations that have been shown to increase breast cancer risk does not guarantee that she won't get breast cancer anyway -- presumably there are causal factors we don't know anything about yet, since the vast majority of breast cancer is not due to one of these familial syndromes -- or any of the other zillions of cancers that afflict humankind. "Cancer-free" may be a misnomer in this case.

And finally, isn't there a morally relevant difference between choosing to terminate a pregnancy because of a positive diagnostic result (eg, Tay-Sachs, Down syndrome) and choosing to do so based on a measure of susceptibility? And no hate mail please: I don't mean to imply that the former sort of case is necessarily the right thing to do...only that some such choices might be more easily justified than others.

The Week in Review

Embryo adoption reopens controversy. Back to the question of when does human life begin, and so what are our responsibilities toward all those frozen embryos out there.

Sports gene test available for little kids. So little Johnny has the genes to be a sprinter, push him in that direction (whether he enjoys it or not)? One can also think of more disturbing uses, like using such a test for embryo election (excuse me, I’ve been in a reproductive rights course this semester, so these issues are top of mind!).

Overseas clinical trials under the microscope—concern whether medical and ethical practices are being adhered to in developing countries. Out of sight, out of mind?

Studies show arrogance and abusive behavior by doctors contributes to
medical mistakes, preventable complications, and even death.

More fallout from the economic crisis—rising stress levels, linked to increases in vulnerability to a long list of illnesses and viruses.

Acupuncture beats aspirin for chronic headache. OK, ancient biotech in
this one!

Computer technology can cut into personalized patient care. Need to enter that data before giving that injection! Admittedly, tech can bring efficiencies, but during an actual patient visit, the tech can interfere in a range of ways. Some inconvenient, yet somewhat comical, like the doctor and nurse huddled over the PC trying to find the code for FluMist before giving it to me. Some rather dehumanizing, like the doctor using up half the precious visit time staring at the computer screen and reading aloud the prior entries before even casting an eye or ear in my direction for the day’s visit.

U.S. study weighs lifetime cancer risks from CT scans.

Fibroid growth differs by race and age.

Gene silencing drug shown to block heart failure in mice (targets a
particular strand of RNA).

British team leads stem cell heart surgery that could end need for
transplants. Patch and rebuild that heart!

Stem cells injected into the brain help stroke patient. Incredible.

Bipartisan report finds U.S. vulnerable to bioterrorism attack. Scary stuff.

FDA sets “safe” levels for melamine in baby formula, despite not being able to say what level is really safe. Does that sentence disturb you as much as it does me? Hey, the levels are significantly lower than the Chinese formula, so that is something.

FDA staff says Solvay’s enzyme pill carries pig virus risks. Comforting.

The more incompetent your boss, the greater your risk for heart attack. Probably not a big surprise, but here you go, study results to back up that gut feeling!

And on a positive note, study shows that happiness is contagious! Spread the joy!

[Thank you to Lisa von Biela, JD candidate, 2009, UMN, Editor of the BioBlurb, from which this content is partially taken and edited. BioBlurb is a weekly electronic publication of the American Bar Association's Committee on Biotechnology, Section of Science & Technology Law. Archived issues of the BioBlurb, as well as further information about the Committee on Biotechnology, are available here.]

Gene testing for Breast Cancer: Hype or Hope?

WBP supporter and personable pundit Art Caplan explains in his most recent MSNBC column that biotechnology firms hope to cash in on women’s fear of the disease:

Fear of breast cancer has created a tempting market for companies to sell genetic testing directly to consumers. The disease kills 40,000 people a year in the U.S., with an estimated 212,920 new cases diagnosed in 2007, according to the Mayo Clinic.

It’s no wonder women would want a reliable gauge of their risk. However, American women should be aware that genetic tests for breast cancer are more hype than real hope.

On Wednesday the biotech research company Decode Genetics of Reykjavik, Iceland, announced it will sell a new test for $1,625 that it claims will allow women “to assess their personal risk for the common forms of breast cancer.”

Genetic testing for all sorts of conditions is all the rage these days. Everywhere you turn, some company is urging you to spit in a cup, take some blood or swab your cheek so your DNA can reveal your health risks, know who your long-dead ancestors are, pick the right mate or help you design a diet that is perfect for your genetic makeup. But, “spitomics” has gotten way ahead of genomics.

Sadly, the tests Decode and other companies are offering are more likely to empty family pocketbooks and leave women with a false sense of security than they are to prevent breast cancer. There is simply not enough federal and international regulation in place to determine which tests are accurate or how heredity interacts with lifestyle to create individual risks.

If the Food and Drug Administration and Congress do not rein in the corporate greed that is currently driving the sale of genetic tests for breast cancer and other diseases and conditions, we could soon have an industry that bears an uncanny resemblance to the home mortgage business.

Marketing for genetic tests is already ubiquitous. The television commercials and magazine ads, which ran in Denver, Atlanta and various cities in the Northeast, promise women that cancer does not have to be “inevitable." They also claim that the average woman can reduce her risk of developing cancer through genetic testing.

Myriad Genetics, the Salt Lake City biotechnology company behind the heavy ad push, charges about $3,000 for a complete risk-disposition test. Myriad, which holds a patent on the first breast cancer test, has been taking full advantage of the genetic testing monopoly it enjoyed until Wednesday when Decode entered the market with its new, more generalized test. To date, Myriad has been very tough about enforcing the patent, even though medical centers in the United States and other countries say they could do the same testing for a much lower cost.

Only small fraction would benefit
In reality, the numbers about detectable risk don’t really back up Myriad’s ad claims.

Of the more than 200,000 new breast cancer cases, only about 20,000 seem to be connected to the BRCA1 and BRCA2 genes — the genes most closely linked to the inherited form of the disease that Myriad’s test can detect. For women without a family history of the disease, perhaps 1 percent would benefit from the test.

On one hand, it would seem to make sense to seek out genetic testing to avoid becoming a breast cancer statistic. Or does it?

Contrary to the marketing messages, only women who have a strong family history of breast cancer — two or more parents, grandparents or siblings who have developed the disease — need to talk to their doctor or a genetic counselor about the value of any form of genetic testing.

Decode’s newer test is not really accurate enough or based on a large enough sample of women to accurately predict much about an individual woman’s chance of getting breast cancer.

If you are worried about your risk of getting the disease, or are thinking about getting a genetic test done for any other reason, talk with your doctor or a genetic counselor who can determine whether your family history justifies the expense. You may be surprised to find that you can make changes in lifestyle and monitoring your own health that can reduce your risk without testing.

The genetic revolution holds much promise for improving our health. Currently, profit and market advantage are playing the key roles in shaping how genetic testing is evolving. These are not the right navigation tools to help women at risk of breast cancer — or the rest of us — capture that promise.

Arthur Caplan, Ph.D., is director of the Center for Bioethics at the University of Pennsylvania.

Original article can be found here.

Smart advice re genetic testing

Today's Newsday includes this fantastic op-ed by Wylie Burke, an ethicist and medical geneticist at the University of Washington, and H. Gilbert Welch, a primary care doc and researcher at Dartmouth. (Full disclosure: I work with Wylie and think the world of her. Read the editorial, and you'll have an inkling of why that is.)

Dr. Welch is also the author of a wonderful book, Should I Be Tested for Cancer? Maybe Not and Here's Why that provides lots more information about the ways in which "predictive" testing and population-level screening can create problems for patients.

Responsible risk communication

Had to share this wonderful op ed from the LA Times. It's about the need for better reporting on breast cancer (and other health risks). It addresses one of my pet peeves with the media, too: reporting relative risk--for example, people with genetic mutation X have a 500% greater than average risk of dread disease Y--without comment on absolute risk (which could be miniscule ... thereby rendering the 500% odds quite a bit less frightening).

The implications of "surreptitious sampling" of DNA

A recent NYT piece by Amy Harmon highlights a law-enforcement practice called "surreptitious sampling," which refers to the collection of an individual's DNA without their permission or knowledge. All of us are leaving traces of our DNA all over the place, all the time: on drinking glasses, kleenex, soup spoons, cigarette butts, etc. If the police wanted a blood sample, they'd have to get a court order; but these discarded or overlooked materials may be gathered by US law enforcement agencies--without probable cause or any oversight from the courts--and used to match samples collected in criminal investigations. If the DNA from the murder scene matches the DNA on your soda straw, you're in big trouble.

At the moment, there's no legal barrier against the Feds' deciding to build a national database of our genetic information to be used for law enforcement purposes. The FBI already has a database of genetic information from convicted criminals, and it has lobbied to make the database more inclusive (eg, to retain samples/data from people who have been arrested but not convicted).

In the UK, a national DNA database has been built that contains genetic information on more than 5% of the population (compared with the FBI's collection on 0.5% of Americans). There's been substantial debate in the UK about the legality and propriety of the resource: you can read more here, here, and here, for example.

Lots of people--including health researchers, pharma companies, insurers, employers, and law-enforcement agencies--would like access to huge datasets of individuals' genetic information. Once such repositories are built (and they are already being built), arguments in favor of a centralized resource are sure to follow, citing efficiency and cost-savings benefits. There are (imo) important privacy and civil liberties reasons to resist such developments.

It's 10:00...do you know where your medical record is?

I've been meaning to blog this once since I saw it a couple of weeks ago: Perlegen Sciences, a spinoff of Affymetrix and a "recognized leader in genomics" (by their own lights) recently signed a deal with an electronic medical records (EMR) company for rights to the medical data of 4 million patients. According to the Perlegen press release, the data will be mined for "genetic markers that could help predict patient response to certain treatments." Patients who meet defined criteria will be sought--through their personal physicians, no less--to obtain samples of their DNA.

The EMR company isn't identified--a smart PR decision, I'm sure--but they will receive subscription and program fees, as well as "milestone payments" for new products that are developed as a result of the collaboration.

I hardly know where to start with this. First, patients' records are being provided, without consent, to a third party. Not for the common good, but for corporate profit. The EMR company will supposedly not share patients' identities with Perlegen--just their records--but it's unclear what happens down the road with genetic information (which is, as I have mentioned here before, not capable of being wholly de-identified). The fact that physicians are being recruited into this process as well--and that they will presumably get their cut--is problematic. The more old-fashioned among us still think that doctors have a fiduciary responsibility to patients that would preclude this kind of behavior.

All this money will likely come from pharmaceutical companies that are vying to produce tailored drugs. When the drugs hit the market, you can bet that the patients whose records were used will not be receiving a price break.

The final straw? The EMR company is not named, and won't be--so patients have absolutely no recourse or ability to opt out of this project.

*******
Edited to add this link to a story on Pharmacogenomics Reporter and another from Healthcare IT News. Apparently I'm not the only person who has a problem with this development: Patient Privacy Rights doesn't like it either.

Testing positive for BRCA: then what?

Studies (here's one) have shown that women tend to overestimate the risk of breast cancer and underestimate the risk of other things that are more likely to kill them--such as heart disease.

But some women really are at substantially increased risk of breast cancer. Specifically, women who have certain identified mutations in the BRCA1 or BRCA2 genes are much more likely to develop breast and/or ovarian cancer. These mutations are rare in the general population, but one expert group recommends genetic testing for women with 2 0r more relatives with breast cancer before age 50, or 3 or more relatives with breast cancer at any age. (deBock et al, 1999).

If a woman has one of the mutations, she has a few options. One is to have more frequent, and more intensive, screening. Another is to have prophylactic surgery: removal of the breast tissue (mastectomy) and/or oophorectomy (removal of the ovaries). In a new book, Pretty Is What Changes, author Jessica Queller tells her story, which began with her mother's death from ovarian cancer and her own decision to have a radical mastectomy in her mid-30s. You can listen to an NPR interview with the author, and read an excerpt from the book, here.

Bringing the genome home ... but why?

This story in the Washington Post gives a decent overview of the growing number of firms out there who promise to improve our lives by giving us insight into our individual genetic profiles. Current players who offer screening include 23andme, Knome (which its founder, Harvard geneticist George Church, wishes we would pronounce "know-me"). Then there are those who claim to provide genetically-based information or advice, ranging from ScientificMatch.com (your DNA is used to find you a suitable date) to Genelex (which offers a mishmash of testing options, ranging from diet advice to predictive testing for periodontal disease) to Navigenics (which claims, "your genes offer a road map to optimal health"). I'm not even going to get into the outfits that offer to trace individuals' ancestry.

Here's a fact about all these businesses: not a one of them is subject to FDA oversight. So all these claims about health benefits, etc., resulting from their services can be completely false (or at least, not based on evidence), and nothing can be done about it. If you read even a *tiny* bit of the scientific literature on genetics and "personalized medicine," you will be struck by how few experts make such claims, at least for the near term. Instead, they talk about the promise of genetics ... while acknowledging that there's an awful lot we don't know. (Along these lines, see this commentary from last week's issue of the Journal of the American Medical Association, featuring none other than the head of the National Human Genome Research Institute.) Bottom line? Given that most health conditions and risks seem to be multifactorial, involving multiple genetic factors as well as environmental influences that we don't yet understand, this stuff is a long way off.

In the meantime, though, consumers should be protected from grossly overstated or unproven claims. Whether that falls to FDA or to someone else (though the Consumer Protection Agency probably has enough work to do at the moment -- lead paint in toys, anyone?), it seems to me the Feds ought to step up on this one.

Free genetic testing ... buyer beware

Following along the lines of several recent posts, another privacy bulletin: a company called Aperture Health has announced that it's offering free genetic testing as part of its Wellness360 program. The program, called geneVIEW, will "uncover hidden diseases--before they have a chance to cause symptoms," and allow you to "learn about your genetic heritage--and know your true history." These are interesting claims, playing into cloudy public perceptions of what genetic testing actually can and can't do, and reinforcing concepts of genetic determinism in both medical and more existential terms. Aperture doesn't offer any counseling in connection with results, though they do suggest that members print their results and discuss them with their doctor or a genetic counselor. There also doesn't appear to be much information available about what, exactly, is tested for if you sign up. These are all things I could go on about for quite some time.

But the really interesting piece here, and the one that some regulatory body somewhere really ought to be paying attention to, has to do with the business model and the protection of privacy. First, the business model: they make their money from (1) advertisers and (2) employers. Chew on what that might mean for a few minutes, and then come with me on a trip through the website.

The section on geneVIEW claims, "Your genetic code is your private property--we'll help you unlock its secrets, just for you to see." In the Q&A section, they say, "At no time is your information shared, sold, rented, loaned or made available to anyone;" but if you dig around, you'll find that they define this protected "private information"as your name, address, phone number, and SSN. So when they say, "We never share personal information about our members with insurance companies, employers or advertisers," it's a little fuzzy just what this means.

Your health information--including, as far as I can tell, the results of your genetic tests--is another story. To find out this stuff, you have to look at their HIPAA policy--not just the privacy policy. Here, they note that they are not a covered entity under HIPAA, but promise to behave in ways consistent with "applicable" rules. Here's what they say about your medical information:

For Services

We will use medical information about you to provide you with treatment and services. We may share this information with members of our provider network or with others involved in your care such as doctors, nurses, or health care facilities.

For Payment

We may use or disclose your medical information to bill and collect payment from your employer for the services we provide to you. For example, we may need to inform your employer that services provided by a Aperture Health provider have been performed and as such, either you or Aperture Health are eligible for reimbursement by your employer.

Third-Party Research

We may use and disclose medical, diet and exercise information to any third-party. The information will be stripped of all information that could allow for the identity of the member. For example, a member's records will only contain, birth date, general geographic location and related information. The member's name, address, phone number and any identifying information will be removed from all records to which third-party access is provided.

What's the upshot? Well, first, there's a pretty good chance that the fact that you've had a genetic test will be known to your employer and (possibly) to your insurer. As I blogged recently, this is an issue to be concerned about. It also looks to me like they can, and will, sell your genetic information--de-identified, for what that's worth--to researchers (a term that isn't defined anywhere I can see). I've blogged some of these issues, too.

There's also this odd little disclaimer:

You may ask that family members or other individuals not be informed of specific medical information. That request must be made in writing to our Designee. We do not have to agree to your request. If we agree to your request, we must keep the agreement, except in the case of a medical emergency. Either you can stop a restriction at any time. [sic]

Yeah. Free genetic testing? This is one "opportunity" we should decline.

23 & Me...Cracking the Code

The issue of genetic screening and analysis--the value and expense of it--and whether the testing is necessary or worthwhile--has been raised and discussed on this blog site time and time again.

The decision to do so, as well as the necessity of it, is ultimately in the hands of those choosing to be tested, based upon their own personal situations. But to what degree--is the testing--and the expense--justified? And would you really want to know what manner of disease and possible genetic defects lurk in your gene pool, dormant for now, but awaiting that deadly trigger down the road, certain to release havoc in your body?

ABC Nightline with Martin Bashir, on Wednesday night, profiled a genetic testing firm, called 23andme that obviously believes that we all deserve and need to know the truth, at a time when there's still a chance to correct it.

Genetic tests and clinical utility

There was a story on NPR's Talk of the Nation earlier this week (listen here) about the array of genetic tests that are now available to you, the consumer. The news hook was a new blood test that researchers claim can define individuals' likelihood to develop Alzheimer disease. Like many other such tests, this one doesn't yield a yes/no answer: it identifies an increased propensity to develop the condition. It can't say for sure whether a person will in fact get Alzheimer disease, or, if she does, what the course of the illness is likely to be. But, for many people, the trouble is not just the certainty of the diagnosis or the accuracy of the prediction.

For some conditions, like Alzheimer's and Huntington's, treatment is limited and cures have not yet been found ... so there isn't anything that a person might do differently to reduce the risk of getting sick. The clinical utility of testing in these situations is limited: the results of the test will not change the medical management of the patient. Some people want such information to help them plan for their own futures and those of their families; others don't want to know and might see such unwanted information as burdensome.

Lots of questions here. Would you want to know? What is the value of information in this situation, and are all reasons for testing equally deserving of respect? Should such tests be available in direct-to-consumer form, without medical direction or involvement--and does it matter if the reason people pursue testing "off the books" is to prevent their insurance company from finding out that they're at increased risk? Should counseling be mandatory, or is that too much paternalism?

Bobby Fisher, Bioethics, and Asperger's

[Hat tip to colleague Terry Tomsick for bringing this to our attention] In a recent MSNBC article, bioethicist Art Caplan ponders the question "Would you have allowed Bill Gates to be born? Advances in prenatal genetic testing pose tough questions". Upon hearing the very sad
news this past week about the death of chess champion Bobby Fisher – I had to ask the same question: Would you have allowed Bobby Fisher to be born?

While we don't know for sure, Fisher's outrageous and at times hateful and bigoted behavior may have been caused by Asperger's syndrome which is part of the autistic spectrum . Or perhaps Fisher suffered from having an "extreme male brain" as characterized by Simon Baron Cohen, PhD, MPhil, a professor of developmental psychopathology in the departments of psychiatry and experimental psychology, a Fellow of Trinity College, Cambridge, and director of the Autism Research Centre at the University of Cambridge, in the United Kingdom, and author of the book "The Essential Difference: The Truth about the Male and Female Brain".

We may never know the truth but it would be tragic if he were simply remembered as a hateful, reclusive genius and not for the many accomplishments he brought to the world.

Dr. Caplan captures the key bioethical challenge these new genetic technologies and our understanding of the brain pose:

As genetic testing moves into the world of mental health, we are going to face some very tough questions. Will medicine suggest that any and every variation from absolute normalcy is pathological? How can we draw lines between disabling diseases such as severe autism and
more mild differences such as Asperger's, which may give society some of its greatest achievers? Will parents have complete say over the kind of children they want to bear? And what sorts of messages will doctors and genetic counselors convey when talking about risks, probabilities and choices that involve not life and death but personality and sociability, genius and geekiness?

Neither medicine nor the general public are at all ready to deal with the emerging genetic knowledge about autism, Asperger's or other aspects of mental health. But the future of our society may well hinge on how we answer these questions.

Bobby Fisher: May you rest in peace.

Home Genetic Test-kits: the new "gotta have it" holiday gift?

Remember home chemistry sets? Well, they're now officially passe since you can get your very own personal genome sequence from one of several fine establishments and do a paternity test in the comfort of your own home.

Beyond simple worries about fraud, there are a number of concerns brought up at DigitalBio, including privacy, liability and legality. I offer up the possibility of overriding GINA (or similar laws, should they ever get passed), and a question: when does information stop being information and just becomes an overload of data that a person does not know how to actually use or parse?