Recently in the Journal of the American Medical Association an article Entitled Genetic Loci Associated with CRP levels and Risk of Coronary Heart Disease...... Long name, useful article....... Why so useful?
Because it proves quite a point.
What is that point?
In most genetic associations the causal relationships are not proven. These studies are merely associations..... Much like what I like to call superstition...... Perhaps you have heard of some of these?
If you spill salt and then throw it over your opposite shoulder you will avoid bad luck
If you break a mirror you have seven years of bad luck
If the cows are sitting down, it's going to rain. Don't leave a fan on in a closed room or it will suffocate the occupants
Don't allow a cat to be in the room with a baby or it will suffocate the babyI could go on here, but I think you get the point. There are millions of observations in this world which are so strong that they get carried on through folklore as if they are correct associations.
I am concerned that this genetic exceptionalism which is in the press and with the DTC genomics companies may create a whole new level of superstition........ "If you have SNP x then you will get disease Y............some of the time"
And it will be self fulfilling......trust me, you will see cases of this coming true being published as anecdotal reports, which will only strengthen this superstition about SNPs and maybe even other genetic findings like CNVs or other rare changes..... This is why I laugh with associations without biology worked out.......
This is precisely what our ancestors did when the kept the sword which wounded them in a cool place to reduce the inflammation of the wound.......
Frankly, I think that using SNPs in this fashion is the EXACT SAME THING....... So these people who are considered early adopters and are "cutting edge" here with 23andSergey scans or CEOs of DTC companies are actually nothing more than CAVE DWELLERS.......This study in JAMA shows a smiliar finding. CRP also known as C-reactive protein is associated with increased risk of heart disease.............there are certain SNPs which are also associated with elevated CRP levels.....so using rat brain thinking, we postulate that the SNPs must ALSO be linked with increased risk of heart disease....... WRONG!!!!rs6700896, rs4537545, rs7553007, rs1183910 and rs4420638 contribute nothing to risk for heart disease, but are significantly linked with elevated CRP.....
Which goes to show that there is a problem which cannot be solved by our current mode of thinking. Because there is a problem with the way in which we think.
And those who huddle together telling stories about there genome scans are nothing more than cave people exchanging superstitions.........
The Sherpa Says: Stick to the science, look for biological explanations and then look for clinical application. Without those things, you have nothing better than a divining rod people! Didn't someone call them Saliva Diviners? HT Misha. Oh, and Francis, Told Ya So in 2008!
A great reader and wonderful lady pointed me to a potential issue with the medications that Michael Jackson was on. She ran them through a site we use to help us with pharmacogenomic issues......GeneMedRX. Take a look at the meds he was on and the warnings in the boxes. I often talk about gene-drug interactions, but what we also need to be aware of is drug-drug interactions.....This software helps. For full disclosure, we see many patients who have had pharmacogenomic testing through Genelex and use GeneMedRX.
You can look at the software here. I find it to be pretty useful webware to quickly go through any potential issues. And on our 32 inch touch screen computers the patient like to look at it while we work through the issues as well......Poor Michael, like all great stars......death by drugs and doctors who can't do med-med reconciliations for potential interactions........
Ok,I am not late to the party here on this one. I have been talking about this for quite some time with posts which include"We have No use for YOUR laws""Who Needs Institutional Review Boards""Steal Your Baby's Genome"I could go on and on here, but this is a natural move here.......23andSergey have decided to move the company into a space which is less likely to get them into hot water with the federal government and in fact may win them a few points with the Federales....Why? Everyone knows the end game here. A huge database of millions of phenotypes paired with millions of genotypes and millions of metabolomes and millions of demographics........With that you create the greatest query machine for human health, generate hypotheses from this and cure mankind of illness. That being said, what 23andSergey have now done is start the "Research Revolution", which to me sounds a lot like Dr Atkins Diet Revolution of the seventies. You remember, the guy who says "I am not really a science guy, but trust me this works"Let me explain why their intention may be very good here. What usually happens in research: The government gives a bundle of money to a researcher or a consortium of researchers who apply for it by writing tedious grant proposals, rather than teach other doctors, students, etc about genetics. Then each institution fights like hyenas over the money to assess institutional fees (also known as indirect costs) Some institutions can take up to 30% of the money before ever getting the research off the ground......(Sounds like another money making scheme to me)Finally after a year of planning and a year of grant writing and a 6 month ordeal with IRB approval, the study is maybe ready to get underway. Often it may take another 6 months of planning. Thus 2-3 years of leg work to get some large study started, another year to 10 to get results......So what has 23andSergey decided? The current research system sucks!Listen closely.......I agree with him, I also agree with the other 23.......The system is broken, probably just as bad as medicine. So what did 23andSergey do? They launched Research Revolution!!! So the first thing I did was look it up.....But I couldn't figure out what Steven Wagenheim had to do with 23andSergeyFinally I corrected the error and landed at 23andResearchRevolutionIt turns out I wasn't late to the party. There appears to have only been 4 people to sign up for this Revolution. Which includes a test for 99 dollars, the inability to keep your own personal genomic data, and of course Sergey!23andSergey have decided that because the system sucks, they will change it by crowdsourcing research, which could be a great thing. IFF you actually had statistically needed participant numbers, research goals, informed consents which go through the process, allow participation for free and an independent IRB......It turns out in the whole "Scrap it and let's start new" 23andSergey have thrown out the baby with the bath water......This could have been a fantastic and it may prove to be a fantastic way to recruit patients and hell, maybe 23andSergey could turn into a CRO organization, but this is no way to do real scientific research, but it is a way to do pseudodscience, like market research........My assumption is that this start up has decided to move away from medicine, way too much heat there, and go further into the marketing, "science", and advertising land. 23andSergey will probably morph into this social network that does pseudoscience, much like their new partner patientslikeme......They can sell their data to pharma and to marketing agencies, they can create the first genomic focus group.....without the ire of medicine and the government.......The Sherpa Says: Hey, be a research captain and get a free T-Shirt with Sergey's face on it......Has all the hallmarks of successful participant recruitment already! Try again. Where is the mention of your IRB? Your ICOB? Your "scientists"? These Guys? Informed consent requires ALL the information. But, hey, at least you have 4, that's a start!
Ok, I couldn't help myself.
Seriously, who takes propofol to get a good night's rest? An Addict. That's who.
Who gives that medication to him?
A crazy person looking to "Democratize" access to propofol.
Come on now.....
You mean it's regulated?You mean, I don't have the right to shoot myself up with whatever I want? What kind of world is this? Communist Russia? Isn't this America, where we have the "Right to Healthcare and Medications"? There is a reason why we have regulations. It is to keep sick people from hurting themselves and others......They exist to keep people alive, they exist to keep people healthy.
Poor Michael needed a good physician, not a weak one who would do things because of money and influence. Rest in peace Michael, I hope my partner's comments didn't hurt too much..... Imagine? Laws to protect people from themselves.........What kind of world is this??? Didn't MJ have the right to that propofol? In a world without doctors committed to do no harm, In a world without gatekeepers, we would see far too much of this....... The Sherpa Says: RIP MJ, your kids will mourn you......Your family will mourn you. Debbie Rowe will mourn you, until the royalty checks come in........
Warning! If you don't want to hear me go off on the Public Relations and Journalism field, click away now!!!!!
Now!!! Seriously, now. For centuries advertising and journalism have existed. In fact there relationship has been one of symbiosis. Think about, papers can't print without money, the money often doesn't come from subscribers, it comes from advertisement's..........This is one of the big reasons why papers are dying.
Online Media Outlets just keep seeing the money flow in though......... Why pay to get marketed to? That is essentially what the savvy news reader is saying.....which is why they have turned away from newspapers and turned towards blogs and twitter......what used to be the gold standard of journalism is now being exposed as a piece of paper for rent to the highest bidder, couched in some official looking headline....
I am afraid the same may happen to blogs and twitter........But this game is not new, the advertising industry has a whole army called "Public Relations" which is designed to do just that, sucker a pressured journalist into "copying" a Press release into an article and send it out "AS IF" it were news.....What really turned the public's attention towards this really, really big scam? Blogs........ Yes, blogs.
The very thing I am writing now.
Why do I know this?
Because I saw it happen........ In 2007 when I started blogging, I was the only, I repeat only voice dispelling the HYPE behind DTC genomics..... The press had been infiltrated by the PR crazies.......
Article after article about how fantastic this would be, without ANY other input from the professional genetics side........or if it was, it was a zealous Ph.D. without any clinical context.......
Drew mentioned the news cycle in most fields with a backlash, that often happens pretty slowly, but with Blogs, it is now sped up.........It turns out that the PR crazies, in an attempt to keep the good times rolling on crappy products and services which don't sell themselves, but instead need millions of PR dollars have turned their eyes to another target...... Yes, the very target that can dispel their hype........luring them with giveaways and maybe even financial rewards..........That is right, Bloggers and Twitterers...... You who write are now the target.....Please tell me you already knew this....... For every PR bastard that I have to filter out of my inbox, to every free fruit drink or textbook I have to throw away, I see it more clearly........ If more bloggers than not are duped by these PR crazies, the blog may actually go the way of the newspaper........ Think about it.
PR has to spend billions a year on newspapers, but they can buy YOU off for a 300 USD SNP kit, or a TOUR of their client's facilities...... It has happened to me. I have been wowed by some wonk running one of the genomic companies. And if it could happen to super cynical me, imagine how many more it could as well.....Don't believe it? All you have to do is read this NYT piece (I know, I just bashed newspapers) about PR's new target...... The FTC realizes this.
They are going to start cracking down on this type of relationship in a way they never could have with the newspapers. Why?
Newspapers have lawyers and money, unlike the lowly bloggers. Just ask me how much it has cost to keep this blog going.........time and heartache......and J.D.'s Which is why I commend people like Blaine Bettinger J.D. who has put on his tweets involving Pathway Genomics, the disclosure that he is a consultant for them.....
I am going to stay away from any paid advisory roles in any of these for profit companies, yes I was offered a medical directorship/advisorship for 2 new startup DTC genomics companies, but I knew I couldn't do it......I would have to scrap my blog, no matter how "The Right Way" they did these things, my credibility would erode, just like the journalists who I no longer read in the WSJ and NYT.......
Luckily, most often, the reporters who publish PR swill are junior anyways.......but in blogging, it could be some of the biggest names.....
So today when I get an email from one of the fathers of genome exploration asking me why I didn't talk about 23andMx's Blimp escapade......I explain that the press can do that, besides, the incestuous way in which the Zepplin, not a blimp came to be was because of pure insider deals, which I am not shunning, but am not going to promote it either........HT Martian Genetics From the NYT:
Gone are the days when snaring attention for start-ups in the Valley meant mentions in print and on television, or even spotlights on technology Web sites and blogs. Now P.R. gurus court influential voices on the social Web to endorse new companies, Web sites or gadgets — a transformation that analysts and practitioners say is likely to permanently change the role of P.R. in the business world, and particularly in Silicon Valley.
So I guess it is just a case of build up your friends/followers list, so you can cash in on them by marketing to them.......just like a salesman would....... The Sherpa Says: I will never sell ads, shill for profit companies, or tell you anything but my god's honest opinion about personalized medicine and DTC genomics. There has to be someone out there willing to do it..........because PR is gunning for us now and we can't let the blog medium turn into a marketing op rather than a vehicle for truth.
A recent study was brought to my attention by a great reader. I highlight it here, not because it is going to change personalized medicine, but because it illustrates some key points.
The study is entitled: "Responses to Online GSTM1 Genetic Test Results among Smokers Related to Patients with Lung Cancer: A Pilot Study" Cancer Epidemiol Biomarkers Prev 2009;18(7). July 2009
This study interested me for several reasons, the first of these was that it involved a hotly debated environmental detoxification gene which has been tested for by numerous nutrigenetics companies for years now. The second reason it interested me is because it dealt with a population who knows that there family can get cancer when exposed to smoking. I have always wondered for years why there are these families out there who have multiple members with lung cancer, yet everyone in the family seems to keep on puffing.
Are these families full of ignorant people who can't put 2 and 2 together despite years of public health campaigns? Are the genetically or environmentally predisposed to smoking? Does the family have some weird death wish set of genes?
I have always wondered why they do what they do. This study evaluates precisely these families....
It was published on GenomeWeb and on several blogs as well as several news outlets with titles like: 1. Online Genetic Testing Appears to have Benefits 2. Study Suggests Online Genetic Test May help Smokers Quit 3. Possible Benefit From Online Genetic Testing For Lung Cancer What they did: They identified relatives of Patients with stage IIIB/IV lung cancer who were receiving care in the Thoracic Oncology Clinic at the H. Lee Moffitt Cancer Center and Research Institute were identified. So in essence, patient who have pretty bad cancer, their relatives....who likely know that it is a bad cancer. They tested the relatives for GSTM1 genotypes. Which is pretty interesting to me, because as the study admits, the Odds Ratio for Lung cancer in this null population is 1.15 to 1.17. essentially as close to one as you can get......
Which means that this association is pretty freaking weak......
So in essence they are going to clinically LIE to the person tested and tell them they had a higher risk.
Oh and BTW, they only analyzed 44 people.....Hardly a useful sample size, especially when 96% were white.....and 22% were college educated, hardly the 23andMx population......
What they found.
1. Smokers with the at risk profile GSTM1 nulls, remembered at 6 months that they had a "higher" risk.
2. Smokers with the normal risk, forgot that more often.....roughly 50% remembered that they were at "lower" risk
3. Both parties "believed" the test results equally........ 4.
There were NO SIGNIFICANT DIFFERENCES in uptake of the smoking cessation services between those who received the GSTM1-present and GSTM1-missing test result....... 5.
At the 6-month follow-up, the proportion of smokers in each group who reported medication use did not differ significantly. 6.
Perceived risk for cancer was the SAME in both groups
7. There were no significant differences over time in confidence in ability to quit smoking between the GSTM1-present and GSTM1-missing relative smokers. "This observational study was not sufficiently powered for nor was it a study aim to assess smoking cessation as an outcome." Obviously as it only had 44 participants in it........ So I am freaking left asking myself "Where in the HELL is the benefit?"
There are a ton of limitations which prevent this article from even being a study. It is an observation of a very, very small cohort......I consider this as statistical NOISE......... But, the authors try to save themselves by stating "However, these limitations need to be balanced against the strengths, which include this study being the first, to our knowledge, to offer genetic testing for a common gene variant online." Are you serious? Strengths? Maybe Strength, but I think that there is other research currently going on involving online genetic testing.
Maybe not published, but there is ongoing...... Some important points that I take from this paper........
1. DTC Genomics has a huge PR machine that will trick papers into writing bull$hit headlines and false claims....I.E. you cannot trust a single thing published in the lay press about genetic studies EVER!!!!!
2. How does a study with 44 people get noteworthy accolades for proving that essentially a single gene variant, weak association, does nothing in terms of empowering patients.....IFF you accept that this study wasn't just noise...... 3. The DTC companies offer THOUSANDS of these little polymorphisms......if the people with normal results can't remember that they are at "REDUCED" risk from ONE, how can we expect people to remember THOUSANDS.....BTW, this is essentially like telling a patient that if they eat a ONE cheeseburger from McDonalds on Tuesday July 16th that they are at risk of a heart attack in the next 5 years......Statistical Bull$hit with ZERO Veracity
4. People will cling to the tiny shred of suspect evidence of the 6 of 44 who quit smoking.......% had the GSTM1-Null genotype, which if you look at statistics is likely pure chance as 50% of the pop is NULL.......Hmm whats the odds of 5/6 being null....I can't believe they even mentioned this in their paper.....What a crock!!!!! The Sherpa Says: Just because it is published in a journal doesn't make it Good Science. Hell, it doesn't always make it Science at all.......Shame on the press and the bloggers who hyped this piece of garbage.......
This is a saying I have been using for about 4 years now.
When someone asked about testing for HFE and why we don't do it as the first screening step anymore.....
They often looked at me confused.....I then bring up the case of sickle cell disease.
Most doctors have seen a sickle cell patient in the hospital.......They may have even seen a family in the hospital, brother and sister, Son and Mother......but what most don't know is that the majority of sicklers never go into the hospital..... That's when I ask, what is the mutation that the son and mother have? The answer Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position.
Now what about the patients who never come into the hospital? Sickle-cell anemia is caused by a point mutation in the β-globin chain of hemoglobin, causing the amino acid glutamic acid to be replaced with the hydrophobic amino acid valine at the sixth position. Why is that? I answer my question as they have lots of guesses.... "No Gene is an Island" You see, there are several things linked to the development of the adverse outcomes with sickle cell disease. Environment, Modifier Genes, Epigenetics (which ultimately is environment) I could go on from there........but suffice to say, genes can only provide us a small answer into the majority of diseases......
Drug metabolism, is a very different story at times..... I then go on to say that there are very, very few diseases for which severity of disease or even disease itself is attributable to JUST one gene........ Or frankly to JUST ONE MUTATION..........
The body is a set of systems and by being super reductionist and looking at one gene or one mutation versus another, we ultimately end up missing the boat and making a big deal out of something which is not so big a deal...... Or we apply something which may be clinically valid but have little clinical utility.......
Even worse, we take something which has wonderful analytic validity and to use it clinically, with a huge waste of money and a huge waste of resources........ This is the case with DTC.
Some may argue that we should allow people to waste their money on anything they want. I tend to agree with this.
However, what should not be tolerated is false claims and manipulation of claims without scrutiny.
In addition, something which meets the definitions of medicine, should be held to that standard......plain and simple........ Taking human tissues/samples and using them for research requires an IRB, taking human tissues and using them to predict risk of disease IS MEDICINE..........and should be regulated as such......
There are a whole host of laws which regulate how a doctor can advertise, why are we not applying them to these companies who are performing such analysis? But more importantly, why are these companies the only people educating the public. And doing a very slanted and manipulative job here...... No Gene is an Island......thus no SNP is the end all or be all of risk.....It is much more complex than that.
Which is why I say "Family History is the cheapest and most clinically useful Whole Genome analysis" The Sherpa Says: Someone is watching these claims, I hope you come here to debunk their junk.
