No more 23andMe blog posts. The Sherpa has achieved his goals.

I am absolutely done talking about 23andMe.

Yes, you have heard correctly.

That doesn't mean I will stop watching what they are doing.

It means that I have coerced them into doing what's right. For now.

From the very beginning 23andMe had potential, heck Dr. Jeremiah Mahoney told me they came up to Yale to see them.

They must have not liked what Yale said, because they went further up the line and partnered with George Church.

Well, they def. didn't like what I had to say.

I had even conjectured about DTCG and what this landscape may look like and even warn about the shortcomings,
I had been pointing all of you to SACGHS to watch where this regulatory environment may go. The environment was heated with these companies going in.

So I knew I had to pay attention to what they were doing, especially the Google Backed company.....

First when these companies launch

1. I immediately point out 23andMe isn't using a CLIA certified lab which gives me grave concern over the seriousness with which they are doing testing. A-la Garage lab versus proper human sample processing.

2. I complain on Daniel MacArthur's blog about the obvious rookie blunder this company with no healthcare experience in leadership makes

Then 23andMe uses a CLIA certified lab

Second, I tell you that the states who have serious laws against DTC will shut down these companies quickly

Then they shut 'em down for a bit. And I gloat


Third

1. I complain that FDA needs to get their act together and in 2009 23andMe began doing absolute truly clinical testing with BRCA testing.

2. I point out the SACGHS feels the same way too and also complains to the FDA

3. I point out that 23andMe has no clinical clue what they are doing with PGx

Guess what? The FDA finally rules for regulation.

Lastly,

1. I complain about this research revolution akin to Tuskegee or other non IRB approved "research"

2. I point out that Google has off shore servers to hold this data free of US regulation.

3. I say that they are coercing subjects and offering discounts that wouldn't fly in an IRB

Today, they announce they have obtained IRB approval.

But I have my doubts as they have flaunted loopholes in laws And seem to point that out again today, or at least their blogger does.....

"our research technically does not require IRB review."

So I guess I will have to keep posting until these guys stop skirting lines..............Nevermind

The Sherpa Says: Yes, why keep it up if they did what I asked? Because they will do it again, even if it takes an act of Congress. Why do I ask? To protect the patient and consumer from mega corporations whose interest is anything but patient empowerment.

What a difference a year makes

It has been one year since I commented on 23andMe's foray into clinical medicine. I was frankly blown away that such a move would be so blatant without integration of health care practitioners.

I also was blown away that Myriad wouldn't sue the ever living bejesus out of 23andMe. A year later, no lawsuit. I am still surprised about this one. Don't you have to demonstrate protection of your patent to keep it?

Maybe Google/23andMe are paying a VIG to Myriad? I don't know, but it hasn't shown up on Myriad's SEC reports yet......

Why was I so surprised? Well, a few months after 23andMe launched the service AND Myriad did not sue, MYRIAD WAS SUED.

I began to wonder if not suing Google/23andMe was a sign of weakness. I was certain Myriad would then shut down the DTC Genomics BRCA testing.

To date, they have not.

This begs the question, does Myriad think they do not have a case and would lose against Google, thus strengthening the case against them by the ACLU? If that is truly the case and we will begin to see judicial activism in patent removal, well, then we could be in for an EXPLOSION of genetic testing labs out there, each doing their own thing, their own way.

An article in Nature Medicine by Brendan Borrell, does an excellent job of discussing the potential backlash and issues related to DTC Genomics and patent holders. They took the tech line. "Should we really be charged to look in the mirror?" Well, do you have to buy a mirror to look in it? FAIL

The question is: "Will other patent holders see themselves as vulnerable by allowing DTC Genomics companies to test for THEIR patented genetic markers?"

This could prompt a huge wave of lawsuits against these fledgling DTC Genomics companies. Normally, companies sue to shake down, scare away competition and make money or at least protect patents. What we could see is lawsuits designed to crush these young companies in an attempt to scare off the ACLU et.al.

By Myriad NOT suing 23andMe, we may have opened up a new wave of patent paranoia and fear. When that happens companies often turn to the courts to scare away competitors and people hell bent on their (patent) destruction......(ACLU)

It will be interesting to see what this year holds for the Gene Patent......

The Sherpa Says: I would love to hear Dan Vorhaus or Gary Marchant's or Barbara Evans' opinions on these things.........

Are you Serious?

While I was lauding Misha ( One of the 10 PGP'ers) and correcting some misconceptions about the PGP informed consent process....something much bigger was happening. I don't know how I missed it...but I did...


Google Buys Into Navigenics!!! That's right...Google now has a stake in 2 of the big 3.......Me? I am the 4th...merely a little guy. Our humble abode is now protected thanks to the NYS and CT Attorney Generals...for Now, well at least until Google can buy New York State.


From Business Week!!


Size of Investment Not Disclosed
Calling 23andMe an example of a company "generating a whole new batch of information of interest to a broad range of people," Pederson says Google wants to extend its capabilities into genetic testing. The precise path and business contours of the emerging gene-testing market remain unclear, but if Navigenics succeeds it "will generate a lot of a very new type of information with potentially far-reaching value," says Pederson. "We felt it was important to get involved now, at the early stage, to better understand the information generated by this fast-moving field."





Did anyone see my post about the Master Plan????? Did anyone watch the Movie??

Read an excerpt from the story



"The Google Story"

Sergey Brin and Larry Page have ambitious long-term plans for Google's expansion into the fields of biology and genetics through the fusion of science, medicine, and technology. . . .One of the most exciting Google projects involves biological and genetic research that could foster important medical and scientific breakthroughs. Through this effort, Google may help accelerate the era of personalized medicine, in which understanding an individual's precise genetic makeup can contribute to the ability of physicians and counselors to tailor health care treatment, rather than dispensing medications or recommending treatments based on statistics or averages.


"We need to use the largest computers in the world," Venter said. "Larry and Sergey have been excited about our work and about giving us access to their computers and their algorithm guys and scientists to improve the process of analyzing data. It shows the broadness of their thinking. Genetic information is going to be the leading edge of information that is going to change the world. Working with Google, we are trying to generate a gene catalogue to characterize all the genes on the planet and understand their evolutionary development.




Geneticists have wanted to do this for generations."Over time, Venter said, Google will build up a genetic database, analyze it, and find meaningful correlations for individuals and populations. . . . Google's data-mining techniques appear well-suited to the formidable challenges posed by analyzing the genetic sequence.It has begun work on this project, but has not been required to disclose any information about it publicly since the work has no impact on its current revenue and profits."




People will be able to log on to a Google site using search capacities and have the ability to understand things about themselves as they change in real time," Venter said. "What does it mean to have this variation in genes? What else is known? And instead of having a few elitist scientists doing this and dictating to the world what it means, with Google it would be creating several million scientists."Google has empowered individuals to do searches and get information and have things in seconds at their fingertips," he went on. "Where is that more important than understanding our own biology and its connection to disease and behavior? With Google, you will be able to get an understanding of your own genes. Google has the capacity to do all of this, and it is one of the discussions I have had with Larry and Sergey."


My business colleauges say "A rising tide raises all ships" But I have to tell you, I am a little worried that they want to end around healthcare not just end arounding IRBs.


My guess. Google will acquire every single bit of DNA database they can get their hands on. Why? Knowledge is power. And they want both.


The Sherpa Says:


Since this is an industry...couldn't we liken this to the XM/Sirius merger? In all seriousness. These corporate genomics companies see medical genetics as a non-scalable model....so they want to get rid of it all together. Flying to the top of the mountain does not get you back down it. I plead with Google, please get some medical guidance. Please!!!!

First Take by Mailund

The first blog response comes From Dr Mailund of Denmark. Thomas is an Associate Professor at the Bioinformatics Research Center (BiRC), University of Aarhus, Denmark.

His response is telling and it essentially says what is true....we would initially be "Lost" but not for too long

My goal is to figure out ways to analyse full sequence data for disease mapping. With full sequences, a few things change compared to SNP chip data.

First, of course, there is the matter of scale. Now you get 6 billion nucleotides per individual instead of 2×500K or 2×1M as with SNP chips. (This is a huge Point!!! This doesn't include methylation and other epigenetic phenomena either)

Second, you are no longer looking for indirect signals, so there are no tagging and multi-marker methods will not be needed to boost the power of indirect signals. You have all the variation observed (but the types of variation is much more complicated).

Third (and perhaps most interesting), the kind of signals we are looking for will change. With SNP chips and tagging SNPs, we are looking for high-frequent variants with modest effect. High frequent variants is all we are tagging (and these have a modest effect if we are still looking for it, if they didn’t we would have found them ages ago). With full sequencing, we will be able to look for low frequency variants as well.

The Sherpa Says:
We would still need more research.......But I am certain it would come in a hurry! Who's next with their take?

Algorithms and Validation

A friend of mine asked me "If the framingham risk assessment fails to take family history into account, then why do we use it to guide anti-cholesterol therapy?" My answer was "It is scientifically validated."

In medicine we like to do things based on evidence. It is true that we do many things that do not have solid evidence behind them. But we always try to acquire data and then make a rational conclusion, leading to a treatment. When it comes to risk prognostication, validation studies are extremely helpful. And often keep us from getting sued.

So what did the Framingham do to be validated?

The Framingham Heart Study and the Framingham Offspring Study were the first epidemiological studies that prospectively collected population based data on the association between risk factors and the occurrence of fatal and non-fatal coronary and other cardiovascular events in a systematic and sustained fashion. It has been dissected for it's validity over the years.

So can we use the Framingham for everyone? Well, in Europe they tried. Several articles like this one show that the risk tool must be validated in the population you plan to use it for. The Framingham doesn't work so well on the Dutch. However when modified by the REGICOR, Spain's NHLBI, it seemed to perform well for the Spanish. The same with the Chinese modification.

You may now be asking what the heck does this have to do with Personalized Medicine. My answer....Everything. You see part of personalized medicine is prediction. That's why Helix Health of Connecticut trademarked "Prediction, Prevention, Privacy" These are the pillars of genomic medicine.

How can you predict the likelihood of Alzheimers in 5 years? Well, there are some corporate genomic companies doing it without having ever submitted articles for peer reviewed publication. They have "Trade Secret" algorithms that calculate risk. What the hell? How can you trust the accuracy of an algorithm without validation?

This is why we advise against using the Gail model for breast cancer risk. It can only work for certain populations, absolutely not for African Americans. There are new attempts at this type of risk stratification, and several attempts to defend the Gail model. But what has evolved is even more important. New algorithms...that were put to the test and peer reviewed.

Which brings me to my last point. What good is a tool if you don't know how to use it, or who it works for? A recent post on Wingedpig points this out. Confusion as to the tools. But what I wonder is what tools they used to create the tools. Would they publish their algorithm? Should they have to? Should other companies who will foray into medicine have to? As for SNPedia...a great resource, but the results are just like a wikipedia....not exactly peer reviewed.

The Sherpa Says:

The votes are in. I am surprised of the results. 23 and Me is the big winner. Why? Well, they specifically state that they do not intend their tools to be used for medicine. Yet all the posts I read have authors who mistakenly are using it as a medical tool. (See the genealogists post "when will they learn") I would have thought the readers would have chosen Navigenics. Navigenics WILL use their tool as a medical device! So I have to ask them. Where are your data on algorithms? Where did you publish and validate them? Which algorithms are you using? I guess we will find out soon enough. 2008 is right around the corner.

Want Longevity? Quit smoking and eat less.....

Yes, quitting smoking and eating less can help you. But it turns out some people will have an easier time doing these things. Also of note we begin to prove Murphy's Hypothesis (There is no such thing as a mongenic disease) These recent genetic studies caught my eye last week.

The first of this is sentinel study (Warning, all sentinel studies require replication)
This study reveals that patients with changes in the Cytochrome P450 enzyme 2B6. It turns out that"individuals with the CYP2B6 6 allele of the gene benefited from bupropion treatment and maintained abstinence longer while doing poorly on placebo, with a 32.5% abstinent rate vs. 14.3%, respectively. In contrast, those in the CYP2B6 1 group did well on both bupropion and placebo, with similar abstinence rates at the end of treatment and after a six month follow-up"

True that we do need some replication on this one, but there does seem to be other literature indicating this trend and other polymorphisms in Dopamine Receptors as well.

In addition to this one an article came out in AJHG this week. I want everyone to give up these words "MonoGenic Disease" Why? There is no such thing as a monogenic disease, unless you only have ONE GENE in your body. An example of this dichotomy is seen in the MONOGENIC DISEASE Hemochromatosis (Which BTW is not monogenic)

Unfortunately most Hemochromatosis is caused by mutations in HFE, but despite this testing, there are still people with Iron Overload who do not have HFE mutations. This is why I am not an advocate of HFE screening or even DTC testing of HFE. Even crazier, different people with hemochromatosis present differently. Why? Because there is no such thing as a MONOGENIC disease!!! In the AJHG this week an article shows that common variants in 3 other genes affect the penetrance of hemochromatosis. These genes are BMP2, BMP4, and HJV.
Serum ferritin levels were all affected by these common SNPs.There was even some indication of synergy between genes. To translate-Hemochromatosis is a multigenic disease, which primarily has problems in the HFE gene. So now is that clear as mud? The point....Don't expect a DTC test for hemochromatosis to tell you 1)If you will have Iron Overload 2)How bad your disease will be.

Finally, before you fall asleep or your heads explode, I want to chat about longevity. Some people think longevity can be bought with hormones, others with vitamins and Nutraceuticals (actually there is better data here). One big group thinks that all we have to do is stop eating.

This starvation group has recently been vindicated by studies on a family of genes called Sirtuins. A recent review was written in the Annals of Medicine. But just a couple of days ago an article in Cell the guys from Harvard Path publish on the role these genes play. Warning. This is a science heavy paper and the clinician may not find it useful at all....Dr Hsien Lei actually posted on this article as well. I see this as a potential windfall for companies looking to create Sirtuin activating cereals..........

The Sherpa Says: Gene Genie is up at Neurophilosophy so check it out! I am tuning up to host the next! We have along road ahead of us.....I like the way we are headed. However, there are some big bumps and changes coming up. Let's all keep our eyes on the prize...Truly Personalized Medicine

Thank You

Today I received a phone call that made my month. One of my wonderful readers called and said "I love reading the Sherpa everyday! You have some way of fitting in really interesting and insightful information that I don't get anywhere else. Trust me, I am on the Internet all the time. No one has this stuff but you! So keep it up Sherpa!"

Let me tell you a little bit about the Sherpa and his (my) day. I usually get up around five am. I hit the snooze button but it never seems to work. Mainly because my daughter has decided to get up as well. I get the baby, change the diapers and turn on the computer. These days I turn on the Treo 700wx as well. I see what emails have transpired while I was sleeping and I get an invoice from my employees overseas.

My S.O. heads to work and I am left alone with my extremely vigorous child. I feed her the bottle while checking the DNANetwork as well as turn on the "news" (what I mean here is the propaganda machine run by PR specialists)

I usually field 2 to 3 phone calls in the morning from my residents. They tell me about how things went overnight in the hospital. Then I hit the shower (yes, even Sherpa's shower)

When I get out, my RSS feeder has finished updating and my daughter has had enough of the PnP (pack and play).

I feed my lovely daughter her bottle and scan the RSS while she is eating, making notes on my Treo. I then take a 5 minute break to give her TOTAL attention. It's 7:15 am, then the phone rings, it is the sitter. I buzz her in (Thank God)

Then the day begins.....I won't share more here. But let me tell you, that part of the day has been a breeze so far.

So I want to thank all of you who read the Sherpa. I appreciate all of your time and attention. Today I want to put something out there for your digestion. AlterNet has posted on something that had worried for sometime (see here). I don't mean to upset the well intentioned people at Google (They are ALWAYS the biggest viewers of The Sherpa according to feedburner) but there are some significant concerns that medical professionals have. Now it is getting some significant play.

Google has been in the info gathering game and has been doing it very well. Unfortunately HIPAA came along and I think the guys in Mountain View have bit off more than they can chew. Do you have any idea how expensive EMRs are? I chalk it up to the HIPAA and billing code abilities that an EMR must possess. Privacy is a big issue even if GINA passes (which it will). GINA does not cover life insurance, secondary schools, potential mates.....etc

The Sherpa Says: I thank you all for listening to my morning. I hope you find as much enjoyment in reading the Sherpa as I do posting it. As for private information moving out of your control, whether you are a utilitarian or an autonomist you have to admit there is something fishy to this type of power grab.

Forbes and Genetics

Way back in 2004 Forbes published an excellent article on inflammation and heart disease. That article introduced me to deCODE. In fact, I was so impressed with their model I began to read about their founder voraciously. More importantly I began to see the wonderful role the media has to play in this new revolution. They can influence the demand just as much as Myriad spending 1 million in Denver to market to consumers. Granted these publications don't have the Oprah Effect (Did I mention that Dr Oz is going to meet the Sherpa?), but they do have some teeth!

But I was also distressed when Forbes published an article that I had a tough time swallowing. In fact it brought me to tears. How can this publication blindly validate and promote these tests without any medical guidance, or suspect guidance at best. I am certain you have all read this article, but you can read it here. The wonderfully hyped name 12 Gene Tests That Could Change Your Life says it all. But before I get into the article, which is misleading and not factual enough to guide decision making, I will investigate the authors via my favorite little spy...uh I mean Search Engine Google ;)

Robert Langreth. He has written many articles some good, some bad. He has been writing about deCODE since 2003 prior to the Big Forbes cover story in 2004. He has been writing about personalized medicine since 1999 as Staff Reporter of THE WALL STREET JOURNAL. He also has written many scathing reports about drug companies, which is why I find it ironic that he endorses deCODE's diabetes test. Which does not tell you as much about your risk as if you had a first degree relative with diabetes. Mr. Langreth was a Staff Reporter at the Wall Street Journal from 1995 to 2000 and an Associate Editor at Popular Science from 1992 to 1994. It was at this time in my search when I figured it out

From a chat in 2002
mherper: What's Kari Stefannson like in person?
LANGRETH: Kari is a charming and very emotional person. He literally had to sell his radical database to an entire country. He did it by a grass-roots campaign, going and speaking to anyone who would listen. He eventually by weight of personal charm won the day over his opponents.
mherper: How can you write about DeCode Genetics when their stock is at $2?
LANGRETH: I wasn't recommending them necessarily as an investment, although I'd argue that it is not a terrible deal right now. I chose them because Kari is doing something that will very likely change the course of science and lead to fundamental discoveries. Whether it leads to a successful business is another question entirely. But since you ask, I figure that unlike many tiny biotechs, DeCode has something unique--the genetic access to an entire country. It doesn't mean they won't go out of business someday. But in the meantime, they are almost certain to have a big impact on science.

Does he have stock in DeCODE??????? It did track up on the day of publication.

We have to be careful to fully investigate our sources. Whom do you trust when giving you information about genetic testing? The company spokesman? The company that sells the tests? What about the middle man? We are entering nebulous waters where the lines of relation can still be hidden. Even from google. When you publish for a peer reviewed journal you have conflict of interest disclosures required. How come we don't have the same for a well read and respected magazine/website?

The Sherpa Says:
Mr Langreth has done some crack reporting on several topics, but to include the DeCODE TCF7L2 test as one that will change your life is a HUGE LIE!!! This test is a party trick at best, a distraction that could lead you to not getting your fasting blood sugar tested (The standard of care for early diagnosis). At best he just boosted deCODE stock. At worst he led you down the wrong trail. Be careful, some who play sherpas actually have stock in the pack the tell you to carry.

Google Innovation? Google Conspiracy? You Decide

In reading through my RSS feeder I stumbled across an interesting video at Testing Hiatus. It comes from the website Master Plan the Movie. Before you watch this YouTube video I first would like you to take a gander at an excerpt from

"The Google Story"

Sergey Brin and Larry Page have ambitious long-term plans for Google's expansion into the fields of biology and genetics through the fusion of science, medicine, and technology. . . .One of the most exciting Google projects involves biological and genetic research that could foster important medical and scientific breakthroughs. Through this effort, Google may help accelerate the era of personalized medicine, in which understanding an individual's precise genetic makeup can contribute to the ability of physicians and counselors to tailor health care treatment, rather than dispensing medications or recommending treatments based on statistics or averages.

"We need to use the largest computers in the world," Venter said. "Larry and Sergey have been excited about our work and about giving us access to their computers and their algorithm guys and scientists to improve the process of analyzing data. It shows the broadness of their thinking. Genetic information is going to be the leading edge of information that is going to change the world. Working with Google, we are trying to generate a gene catalogue to characterize all the genes on the planet and understand their evolutionary development. Geneticists have wanted to do this for generations."Over time, Venter said, Google will build up a genetic database, analyze it, and find meaningful correlations for individuals and populations. . . . Google's data-mining techniques appear well-suited to the formidable challenges posed by analyzing the genetic sequence.

It has begun work on this project, but has not been required to disclose any information about it publicly since the work has no impact on its current revenue and profits."People will be able to log on to a Google site using search capacities and have the ability to understand things about themselves as they change in real time," Venter said. "What does it mean to have this variation in genes? What else is known? And instead of having a few elitist scientists doing this and dictating to the world what it means, with Google it would be creating several million scientists.

"Google has empowered individuals to do searches and get information and have things in seconds at their fingertips," he went on. "Where is that more important than understanding our own biology and its connection to disease and behavior? With Google, you will be able to get an understanding of your own genes. Google has the capacity to do all of this, and it is one of the discussions I have had with Larry and Sergey."

Ok, So now you can watch the movie at Testing Hiatus

Let me know what you think. Does Don't be Evil mean Be Good? Or Does it mean something else?