Sunday, July 18, 2010

Protection or Paternalism? - Part Three on 23andMe's Genomic Policy Forum

SURGEON GENERAL'S WARNING: DTC genetic testing delivers information that could cause you to jump off a bridge, cut out an organ and may complicate the health care industry's ability to maximize their profits.

After my Part Two blog, I realized, why shouldn't I be outside taking advantage of the nice weather? Times have changed! So, here I am now blogging at the beach and wondering why, in this digital age, the medical community is still struggling to digitize our medical records.

For us personal genomic enthusiasts the question of the day is: Will impending regulation limit our right to have access to our genetic information and, if so, to what extent?

I am told that when deliberating on regulation, the FDA uses a risk-vs-benefit model. They consider potential adverse outcomes for the consumer when deciding how and when to regulate. As of late, there is this fear of consumers making adverse decisions based on their DTC genetic test results. Is this a well founded fear? The question that I posed to the panel in the final segment of 23andMe's genomic policy forum on Wednesday was this: Is this risk a real, demonstrated one or an imagined one?

This is not a brand new industry. In fact, several companies have been providing genetic profiles long enough that we should be able to get a definitive answer to this question. Have there been any real life, significant examples of adverse outcomes or harm done to a customer during this time? Since any industry has some incidences where a customer has had an adverse outcome, one would imagine there must be some in DTC genetic testing, right? Other than the over-sensationalized stories of late that have turned out to have no reported long-term consequences, where are they? If the few people involved in the recent, much covered, sample mix-up are tired of being hounded by reporters (which they are) and national reporters are having to aggressively seek negative experiences from DTC consumers (Daniel MacArthur's Genetic Future blog), with some even going so far as to exaggerate the comments of the ones they do speak with to give them a more negative slant, doesn't that, in itself, tell us something?

Opponents of DTC genetic testing are raising the spectre of distraught consumers jumping off bridges or cutting off body parts for knowledge of their risk factors. (Since when can you cut off/out body parts without first consulting your doctor and then without the the aid of a surgeon anyway?) In sharp contrast to some of the FDA approved pharmaceuticals that have proven side effects, including death, where are these adversely affected consumers?

Are we regulating for the lowest common denominator or for the reasonable consumer? Any reasonable customer when confronted with what they perceive as disturbing test results, will go to their doctor to inquire about it. The doctor can, in turn, weigh the environmental factors and medical history and advise the patient. For example, if a woman tests positive for the breast cancer gene, can she choose to undergo a double mastectomy without a doctor's input? Of course not.

The only potentially authentic risk that I heard presented at the forum was one of the patient/consumer deciding to forgo regular check-ups because they feel they are not at risk for certain illnesses. People make, arguably, worse health decisions without interference all the time. Perhaps the government should regulate fast food consumption and institute mandatory work-outs, like gym class in school. How about the fact that consumers have direct access to cigarettes and alcohol, both of which have demonstrable risk and place an immense burden on society? If the FDA and Congress are so concerned about the public's well being, then why not deny or heavily regulate access to these unquestionably harmful choices? Perhaps because there is no perceived economic gain in doing so, while sadly, there is never-ending and ever-increasing phenomenal economic gain involved in the treatment of obesity, diabetes, heart disease…the list goes on.

For approved dangerous pharmaceuticals, it is said that the benefits outweigh the risks. But what are the side effects of education and information? Are we being protected from ourselves? If we are going to consider the risks posed by DTC genetic tests, then we also have to consider the benefits. Adverse outcomes get lots of press, but what about all of the quiet benefits and successes? How many children won't suffer from Mendelian-type diseases because their parents learned of their own carrier statuses from DTC testing before reproducing? How many people who have put off visiting their doctor may be encouraged to do so from the results of their tests?  How many of these private, individual stories will we hear? In this, I can speak from my personal experience. To my surprise, my 23andMe test results showed that I am a carrier of Cystic Fibrosis. I would never have imagined my genes held that secret because nowhere in my extended family history has this disease ever made an appearance (and being a genealogist I know my family's medical history). This discovery inspired others in my family to test to determine whether they are also carriers. This is especially important knowledge for my five nieces of child bearing age. How many other families will be forewarned and, as a result, knowingly avoid tragedy. Will we ever know?

How about all of the people who are motivated to healthier lifestyle choices by finding out that they have a potentially elevated risk for a certain condition? Again, I can speak for myself in this arena. Among my risk factors are several diseases that can be combated with healthier dietary choices. Did I already know that I should be eating more fiber or green leafy vegetables? Of course I did, but there is something so intensely personal about your own DNA being the one to warn you that, somehow, you finally listen. I know that I am not alone in this.

Maybe, instead of focusing on these anticipated adverse outcomes from DTC testing, we should be asking: How many adverse outcomes may be AVOIDED as a direct RESULT of DTC genetic testing? 

The airways are blasted with commercial messages depicting smiling “patients” gardening or leisurely strolling the beach at sunset as we hear about the gruesome side effects of the drugs they are promoting. I guess its okay with the FDA to take drugs for depression because if you die from rectal bleeding from their side effects, at least you’ll die with a smile… and if your erection last more than four hours you should call your doctor because you COULD die from it, but, well, what a way to go…(and what a great marketing ploy...) So, then, it begs the question: What are the potential side effects of a DNA test? Is it that we will be given information that we are too stupid to handle? Is it that we can’t handle the information that we are given? Is it that someone – for your own good – must look at the information, interpret it, edit it, if necessary, and then decide whether or not to let us see it? Well, isn’t it good to know that someone is looking out for us … protecting us against ourselves? Or, does it sound a little too much like the Orwellian Big Brother looking over our shoulder?… OR, does it sound the most like: The business of personal genomics is predicted to become, perhaps, the most lucrative industry of this century, and we’d better make sure that we get the lion share of it…because, well, we really care about you, really, really care…?

In 2008 the AMA adopted policies opposing DTC testing (here) and said that they want to be the ones to decide who should have a DNA test and when. In the Pharmacogenomics Reporter Turna Ray reports:
The nascent direct-to-consumer genetic-testing industry has so far kept physicians on the sidelines by asserting that individuals have a right to view their genetic information, but the nation's leading physicians' group recently said that MDs should play a central role in determining when and on whom a genetic test may be performed. The American Medical Association during its annual meeting in June adopted a new set of policy recommendations that seek to heighten the role physicians play in administering genetic testing by making them the go-between separating genetic testing companies and consumers. 

Does that sound self-serving, or is it just me?

And now, finally, we have come full circle back to the reason I attended 23andMe's forum in the first place - one that I cannot ignore - Ancestry DNA testing. Personally, I feel even more comfortable with my decision to test with 23andMe for my health risks because they include my ancestry information in my profile. This functions as an unintended safeguard. As has already been demonstrated, in the rare event of a sample mix-up, the ancestry portion is what will alert us to the problem. It would be a mistake to separate these two types of tests in the process of subjecting one or both to strict regulation. Furthermore, it would be completely without foundation to enact restrictions on Ancestry DNA testing itself since it neither carries real nor imagined risks.

So, maybe the most burning question we should be asking ourselves is this: Why all of this focused attention now - from the FDA, from Congress, from the AMA, from the media? Should the decision to regulate be influenced by those who directly or indirectly benefit economically from such regulation?  Regulation may be essential to ensure quality and accuracy from the companies providing these services, but it should not infringe upon our right to directly and privately access this very personal information.

Saturday, July 17, 2010

Washington Post - Can we take the higher road?

Rob Stein's Washington Post article today was not as negative as some had feared. In fact, overall, it was fairly well balanced (especially since he let me have the last word :-) ). However, I have some real issues with its leading paragraph. Mr. Stein interviewed me about my experience with the 23andMe sample mix-up and asked me to put him in touch with others involved because, apparently, he was having a difficult time finding negative DTC testing experiences to write about in his story.

Why would a responsible journalist from one of the country's premier publications open an article about a subject that has so much promise (when we know most people never read beyond the first paragraph) with the following:

One woman panicked when the genetic test she had ordered over the Internet concluded that her son was carrying a life-threatening disorder and, even more disturbing, that he was not -- genetically -- her son. Another, who always thought she was white, was flabbergasted to find her genes were mostly of African origin. A third woman's result was still more stunning: She was a man, it said.
"I thought, 'Oh my God. Am I really a man?' " said Denise Weinrich, 48, of St. Peters, Mo. "I thought, 'What's the matter with me? I'm not who I thought I was. How am I going to tell my children?' DNA doesn't lie."

1. "carrying a life-threatening disorder"  - This is misleading. According to her post, the test said that her son was a CARRIER of hemochromatosis. Most people who read this phrase will interpret this to mean that she was told her son HAD a life-threatening illness.  23andMe reports data for two mutations in the HFE gene - C282Y and H63D. It is estimated that, respectively, 11% and 16% of Northern Europeans are carriers of these mutations and they have NO symptoms. Even for the majority of the people who actually have this disease, it is not life threatening. The choice of words is ambiguous at best and sensationalized at worst. (More info on hemochromatosis here.)

2. "flabbergasted" - This is a misstatement. I know this because the person to whom Stein is referring is my niece. He never spoke to my niece directly and I never said, nor implied,  that my niece was "flabbergasted." Actually, I expressed the exact opposite to Stein. First of all, I told him that when she initially called me about her test, she very matter-of-factly stated, "My genes are most similar to a Nigerian" with, surprisingly, little reaction.  Secondly, I told Stein that I immediately informed my niece that it was a mistake, so there was never any real question of whether she was actually African genetically.  How he got "flabbergasted" from that, I do not know.

3. Denise Wienrich - Her experience has been an overwhelmingly positive one, so why must it be portrayed in the worst possible light? Here is what she wrote to me via email this morning,

"This is so sad....95% of what I said was how thankful I am for the testing...Told the story of my adopted children and the 30+ Guat(emalan) kids who also tested with 23andMe. How I would never want DNA testing regulated because it would be hard to do for cash strapped adoptive parents, etc.  

No wonder people complain about the interviews they give to reporters."  (bold mine) 

This entire debate flared up because of a lab mistake which led to the accidental reporting of misleading data in the very complex world of personal genomics. Why insist on opening the article with an ostensibly intentional and misleading statement in what should be a very simple exercise in reporting the facts – journalism? Here we are at the cusp of something widely recognized, even by its critics, as holding the potential of becoming one of the largest revolutions of health care in history - personalized genomics.  Can’t we take the higher road?

Thursday, July 15, 2010

Unexpected Enightenment - Part Two on 23andMe's "Genomics and the Consumer" Policy Forum

Its almost a month into summer and I am still too transfixed by personal genomics to take advantage of the sunny SoCal weather. I am not a scientist, but, rather a highly engaged consumer of DTC genetic testing. I, like many of you reading this, am an early adopter of this DNA testing that enables a glimpse into the age of personalized medicine - our future.
Yesterday, I had a most enlightening experience at 23andMe's genomic policy forum. I attended as a genetic genealogist concerned about impending regulation and how it will affect genetic ancestry testing, but emerged with an unexpected view of the future of health care and as an educated and dedicated consumer of personalized medicine.
23andMe assembled an excellent group of experts in the field of personal genomics. Apparently, having a favorable opinion of DTC testing was not a prerequisite for inclusion. Instead, and as it should be, the participants were chosen because they are some of the brightest minds engaged in this burgeoning industry today.
In his keynote address, Dr. Leroy Hood presented a compelling argument in favor of integrating our current health care system with analysis of personal genetic profiles as soon as possible. Although we still have a long way to go in deciphering the human genome, there is already highly beneficial genetic information that can be interpreted and utilized for each of us. According to Dr. Hood, much of the medical establishment is currently resisting this absolute eventuality. He wants us all to realize that there is potential for enormous economic gain for those corporations and/or individuals that, instead, embrace it and successfully solve the conundrum of how to facilitate and innovate this revolution into the age of personalized medicine. He discussed a time not too far off when each of us will a carry a chip with our genetic profile and wouldn't imagine getting medical treatment without it, when babies are genetically analyzed at birth, when people are assigned drug regiments based on their genetic risks and all of us will engage in what he calls "P4 Medicine." ( P4 Medicine = Predictive, Personalized, Preventative and Participatory Medicine.) Dr. Hood is confident that "P4 Medicine will drive an economic health care revolution," and predicts that it will become "one of the most powerful public and private investments of the 21st Century," while dramatically lowering overall health care costs.
What does all of this mean for the ordinary consumer? Obviously, it is in the public's best interest to have access to the most efficient and effective health care. So, what can we, as private individuals, do? Educate yourself and your family. Encourage your friends and colleagues to support the legitimate companies that are the visionaries in this new venture. Encourage ground breaking coursework in our universities (like Stanford's controversial offering). Or even, go back to school and become one of the much needed professionals who will actively participate in this revolution.
If we resist progress, ultimately, we will lose out. With too many impediments, these innovative companies and thinkers will be forced to take these advancements elsewhere and, as a result,  the US will not be at the forefront of this revolution.
Health care is a consumer driven business. As was astutely pointed out by one of the forum's panel members, Dr. Sandra Lee of Stanford, the line between patient and consumer is a blurry one.  Supply follows demand. Be vocal. Ask your health care professionals to incorporate genotyping into your care. Tell your elected officials that this is an important issue to you. Patronize health care facilities and companies that recognize the importance of genetic research and support its advancement.  Most of all, don't be one of the hold-outs. Personalized medicine is our future and it is to all of our benefit that it come sooner than later. There is a place for skepticism, especially in medicine. However, when we learn that something as benign as the Human Genome Project faced decade-long resistance (as Dr. Hood told us), it begs the question, What exactly are they afraid of?

To be continued in Part Three...

Part One - Overview, "Genomics and the Consumer" Policy Forum

The First in a Series of Articles on 23andMe's "Genomics and the Consumer:The Present and Future of Personalized Medicine"

I was very fortunate to attend the "Genomics and the Consumer" Policy Forum organized by 23andMe yesterday. It was an impressive line-up of speakers, panelists, and moderators. Even the attendees were of an extraordinarily high caliber. California State Senator Alex Padilla was an able and well-educated host. It is encouraging to find that one of our elected politicians is well versed in such a complex science and aware of its great importance. 
What was especially interesting is that this was not an exercise in mutual admiration and patting each other on the back, as one might expect in a room full of academic elites invited by a for-profit corporation, but rather a healthy debate of differing, sometimes conflicting and even critical viewpoints. In the midst of all of this intellectual discussion, the common goal was to find ways to integrate reasonable standards and regulation in this blossoming industry that holds tremendous promise for revolutionizing our health care by incorporating the ever-increasing knowledge about the human genome.
As Dr. Leroy Hood pointed out in his keynote address, this is a revolution not an evolution.  Personal genomics is changing the rules in health care. All seemed to agree that the biggest challenge that we face is how to get everyone on board. Dr Hood calls it “the people problem.” And, really, that is what this forum was all about - the people problem. How do we come together as a society, so we can realize the potential great benefits of the advances in the field of genetics? According to Dr. Hood, “democratization of health care” can be accomplished.
Perhaps the day was best summed up when a consumer spontaneously stood at the microphone and proclaimed, “DTC genetic testing changed my life!”  She went on to relate how, without medical coverage due to a pre-existing condition, she was able to discover through her 23andMe genetic profile a potential life-threatening condition and was inspired to take simple and practical steps to lessen her risk. This served as a healthy reminder why we were all there. Each and every human being can and should be given the opportunity to take responsibility for their own health.
Change is always difficult for the already established medical field. Attendees and participants differed in their estimates as to how long it will be before we reap the benefits of personalized medicine. However, there was a consensus on one thing, it is coming.

Part Two - Unexpected Enlightenment at the Genomic Policy Forum 

Monday, July 12, 2010

DTC Genetic Testing and the 23andMe sample mix-up - My experience

I am revisiting this subject since it is, apparently, still an area of interest for media and consumers.

I am the genetic genealogist in the family, so I am always encouraging family members to test. When the recent $99 sale took place at 23andMe about 15 of my relatives purchased tests, mostly because they were interested in the health portion of the results. In particular, my niece and her husband both purchased tests to determine if they were carriers of any Mendelian disorders, i.e.-cystic fibrosis, hemochromatosis, etc... so they would be aware of any potential issues when the time comes to start a family. Both of their results came in on the evening of June 1st. Since I have spent countless hours educating myself on these tests, it falls to me to help interpret them for my family members. With 23andMe, the health results usually arrive shortly before the ancestry portion. Nothing jumped out as glaringly wrong until the ancestry results started to appear. My niece was listed as having an African maternal line haplogroup. Since she is my sister's daughter, we should have the same mtDNA haplogroup, but did not. My mother and myself both tested as 100% European with U5b1b2 mtDNA. I immediately knew that there was a mistake, but thought that maybe it was just a software glitch that would be resolved overnight once all of the ancestry results were fully populated. When I woke up the next morning, I checked and her Ancestry Painting had come back as 69% African and she did not match me or her grandmother on any DNA. This was obviously a mistake, so I wrote to 23andme (9:22am) and immediately received a response (9:26am) that they would look into it and get back to me. From that point on, I had an ongoing open line of communication with 23andme. I checked the community forum and posted on the ISOGG (International Society of Genetic Genealogist) mailing list and the DNA-Genealogy Mailing List. Working as a community, very quickly we determined that there was a mix-up that affected quite a number of people and I communicated that back to 23andMe as had one of their consultants who is also a member of the genetic genealogy community and ISOGG. 23andMe was very quick to respond, removing the affected batch and sending out an email to all those affected well before the end of the day. Some even received phone calls.
23andMe was quick and efficient in their response. Alex Khomenko should, especially, be commended for jumping in and engaging with the community, putting fears to rest and communicating what they knew as soon as they knew it.
The fact that the genetic genealogy community was so quickly and competently able to determine that there was a mistake and communicate that to the company involved and disseminate that information to others who may have been affected, clearly demonstrates the strength and efficiency of self-regulation. Had each of these 96 results been delivered separately through health care professionals (who have no reason to communicate with each other), instead of  through a large, highly communicative, actively engaged community, the less obvious cases may have escaped notice. How often must it happen that individuals receive incorrect lab results and never know it? A blunder like this in the medical community may never have become public and, certainly, not this quickly. This snafu actually is a good example of successful self-regulation through transparency and should be seen as an argument against outside interference, instead of an excuse to intrude in an already efficient and altogether benign industry.
If this industry is regulated by outside agencies, it will, most likely, take away the anonymity that exists presently in privately receiving your results. Who will want to test, knowing that the results will immediately go into your medical records and potentially be held against you by insurance companies?  Right now, there is no chain of command, meaning that, if I so choose,  I can test under an alias and still have access to my personal information, while no one else ever has to know my results. If that changes, I believe very few people will test, effectively crippling this emerging industry and crushing the valuable research and advancements that are presently being made.
The recent move by the FDA to regulate this industry is misguided at best and sinister at worst, but hardly surprising. We live in a society where every day it seems efforts are made to remove our individual rights by "Big Brother" or big corporations. One would think with the epidemic of rising health care costs, the public would be encouraged to educate themselves and take responsibility for their own health. By attempting to refuse us direct access to our genetic information, the regulators are stomping on our rights as Americans. They are doing it under the guise of "protection," but isn't it really about power and profits? We have entered a new age of personal genomics and are on the cusp of epic progress that can only be halted by government interference and "Big Brother" mentality.

"Genetic Testing Company's Mix Up Stirs Regulation Debate" from Fox News - Quotes from "Your Genetic Genealogist"

San Francisco Chronicle "Gene test mix-up brings scrutiny to industry" - Quotes from "YGG"

Sunday, July 4, 2010

Comparison and Analysis from 23andme's Ancestry Finder

After working with my Ancestry Finder tools for awhile, I have done a few basic comparisons. Any chart can be viewed larger simply by clicking on it.

Here is my basic view:
 Here is my mom's basic view:
You can see that my mother has many more Finnish segments than I do, but I have a substantial Irish segment on Chromosome 11 (11.3 cMs) that my mom does not.  From this, I can deduce that my father passed me this segment. This begs the question, "Did my father have Irish ancestry of which I have been previously unaware or is this Irish ancestry connected to his immigrant British Australian grandfather?"

Here is a shot to show the information that is displayed when the cursor is moved over a colored segment:

Here is a shot of my overall Finnish segments from the Advanced View. In this shot, I chose a minimum segment size of 5cMs and matches who have grandparents from up to four different countries. When the cursor is moved over the Finnish column, all matches except Finnish ones fall away.
Here is the view of my mom's chart with the same settings:

These charts show the effect of the Finnish contribution being halved in my genome. My mom is 50% Finnish and I am 25% Finnish.

Here is my full advanced view set at a minimum of 10cMs:
Here is my mom's with the same settings:
Notice that she does not have any matches on the X Chromosome at this setting, but I do. Therefore, my match must be from my dad's X Chromosome. Since my dad's X only came from his maternal side that narrows it down to Norwegian or Australian English origin.
Let's take a closer look. This is what my X match looks like with the cursor hovering over it:

From this analysis I can deduce that this match who has three grandparents born in Canada and one in the US is related through my father's mother's ancestral lines. Interestingly, so far on Relative Finder I have no known matches on my X Chromosome. Therefore, this example also demonstrates that this tool is providing information that was previously unavailable to us.

Lastly, take a look at my chart with the segment setting at a 10cMs threshold and matches with (at least) three grandparents born in the same country:

 And my mom's at the same settings:
From comparing these I can see my father's contributions (Ireland and Canada) among my matches on the chart.


Here is the Tutorial  Screen:

And the Advanced Controls Help Screen:

My Conclusion:
I believe this tool will prove to be useful to many of us and, at the very least, interesting and entertaining to the rest. It gives us an overall look at the ethnic background of our genetic matches as well as our parents' individual ethnic contributions to our genome if we have been able to test at least one of them. Further, as demonstrated by my match on the X Chromosome, it does give us some limited information that was previously unavailable in regard to some of our matches on Relative Finder who have yet to accept our many outstanding invitations. That, in itself, is a positive step forward. Keeping in mind the inherent limitations of an application that utilizes user-submitted data that's scope only reaches back a couple of generations, in my opinion, this is a welcome addition to the tools available to individuals in their quest to discover as much as they can about their genome.

X-Chromosome Testing vs. mtDNA Testing

Judging from all the questions I have been getting, apparently, there is a lot of confusion about mtDNA vs. X-Chromosome DNA. They are completely different things.
mtDNA or mitochondrial DNA is outside the nucleus of the cell, as opposed to the 46 chromosomes (23 pairs), which are located inside the cell nucleus. Inside the cell nucleus, there are 22 pairs of autosomal chromosomes plus the sex chromosomes (the X and the Y). In addition to the other 22 pairs of chromosomes, females inherit two X Chromosomes (one from each parent) and males inherit one X Chromosome (from their mother) and one Y Chromosome (from their father).
mtDNA is passed matrilineally. That means it is only inherited through the female/maternal line. Men do inherit their mother's mtDNA, but they do not pass it down to their children.
Men also inherit their X Chromosome from their mother but, in contrast, they DO pass their X Chromosome to their daughters. However, they do NOT pass their X Chromosome to their sons. Further, the X Chromosome that a male inherits from his mother has genetic material traceable from many more of her ancestors than the mtDNA that he inherits from her. The X Chromosome will also include DNA from some of his mother's PATERNAL ancestral lines, unlike the mtDNA that only traces through her direct maternal ancestral line.
It is complicated, but it will become much clearer to anyone who studies the charts below on X-inheritance patterns and mtDNA inheritance patterns.

Here are some good charts by Jim Turner ( illustrating X-inheritance patterns:

Click on the charts to see them larger or go to the link of origin:

In contrast, here is a chart from Angela Cone showing the mtDNA inheritance (on the right side in red only):

As one can see, the numbers of ancestors contributing to the mtDNA is much more limited than that of the X Chromosome. Therefore, X Chromosome testing has the potential of tracing many more ancestors than mtDNA testing.
For further study on this subject, please see Sorenson's animations here and watch both the mtDNA and X Chromosome videos.