Some Confusion Exists

I have a great comment string going on with Daniel MacArthur over at his blog Genetic Future

I think there is some confusion going on here and I place blame on just about everyone in this space who has a mouthpiece.......

But mainly I lay blame on the marketing teams for the Direct to Consumer Genomics companies.

These companies have an interest in making you "think" that their products have some particular health relevance.

Otherwise, no one in their right mind would waste their time with these tests.......Other than the HUGE field of ancestry buffs like Blaine Bettinger J.D. (woohoo) We need clarity here.

From Daniel- "The American College of Medical Genetics is saying "Genetic tests of individuals or families for the presence of or susceptibility to disease are medical tests."

The fine print says:

"This guideline should not be considered inclusive of all proper procedures and tests or exclusive of other procedures and tests that are reasonably directed to obtaining the same results. In determining the propriety of any specific procedure or test, the geneticist should apply his or her own professional judgment to the specific clinical circumstances presented by the individual patient or specimen"

Meaning

"The judgement of what constitutes an inclusive test is left up to the physician"

In my opinion, there are Green tests, Yellow Tests and Red Tests. I think Ryan Phelan sized this up pretty eloquently in 2007 at a conference I spoke at with her.

Red means - Stop, does this test need analytic/clinical utility/validity? Yes, Go ahead and regulate, these are clinically validated/used clinically for a long time, tests which have a use in medicine. If this test is claiming to do so but does not, then this too should be a cause of regulation.

Yellow means - Well, this could be used but maybe hasn't yet. I think of Age Related Macular Degeneration testing. They could have clinical applicability and haven't been put to use yet. This category may also include low odds ratio common SNPs here which indicate risk FOR disease.

You should have some caution when selling/regulating these tests. The biggest problem is that with evidence evolving over time the low ORs may actually be overturned or fall into the Red category.

They key point is what the test claims to do here.

Does it claim to tell you a risk for a disease via algorithm etc.?

If yes, then it becomes a Red test.

If it says in huge disclaimers, this test DOES NOT PREDICT DISEASE RISK, in plain and clear writing on every piece of its marketing then Yellow tests stay Yellow.

Green Tests - Have absolutely nothing to do with a person's health. These tests do not need medical regulations. Ancestry could be here. Eye color/ear wax/height.

But the moment it is used for medicine or medical procedures (PGD for these things, scary but possible) it then becomes a Red test.

ACMG is talking about Red tests. It is also saying, if you as a clinician think a Yellow test is actually a Red test, then it is a Red test.

Which I agree is confusing. But ACMG is not the US or State Governments. Nor is it the UK or anywhere else's government......It is a professional organization.

My take is simple. If there is a risk for public harm, the government should protect its citizens from that harm in a reasonable manner. I emphasize, reasonable manner. What Techies in the Silicon Valley view as unreasonable regulation may very well be extremely reasonable in the view of physicians and hospitals......

There is no reason to get all crazy here. The New York Times is right, until the government or state governments step in to protect the citizens of risk, it IS Buyer Beware when it comes to genetic tests.....

In my mind, genetic tests need to prove their worth in the field of medicine. They do this by medical science and clinical science studies.

Without these, they are useless noise.

So, should you be able to buy useless noise?

Go ahead.

But the moment the noise whispers in your ear "PSSST, I can tell you your risk for diabetes for 50 dollars" Its A$$ should be regulated.

I hope that clears things up. The problem here is that you have a company selling you noise mixed with clinically valid tests. They are the first company whose A$$ should be told to hold up and split the products.

Then you have a company selling you noise all the while "inferring" it is actually predictive and useful in medicine by getting Doctors to use it in medicine should also be regulated.

Blame Marketers and Spin Men, just like "Thank You for Smoking"

The Sherpa Says: If you apply the Red, Yellow, Green interpretation scale you will soon understand why all the confusion exists. And how that confusion can be cleared up.

Family History, State of the Science

The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?

With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment

There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by..... A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......

4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.

-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!

Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Lots to recap today.

First, in support of Francis Collins' efforts. I am a God believing scientist/physician. Why? Can you explain "spooky science" of photons? No? Are there some things in this world which are a mystery? Yes. I choose God to explain that mystery for me.

Because as a human it is beyond my ability to conceive of it. Maybe someday Singularity will "save me" but I doubt it.

Second, To explain Germany's move without resorting to "It's designed to make doctors money"

Which BTW is the stupidest argument I have ever heard coming from a country with Nationalized Medicine. Doctors make what they make and that's all. Why try to find new revenue streams for someone who's salary is capped? Do they really think this would bring Doctors to their country? Wrong!

Here's why they are outlawing this and why comparative effectiveness research in the US will end up costing some useful therapies their market.

Think that the person is not an individual, instead it is a money making machine for the largest company in your country. The government. The government makes its money through taxes.....it expends its capital supporting people who aren't so good at paying taxes as well as a whole host of other things, like defending you from nasty people looking to destroy your way of life. Why do they support those who don't have jobs and aren't healthy? They do this in hopes to get them stable enough to pay taxes again. Thus a new revenue stream is created.

If they can keep you healthy so you pay taxes, that is a big win. If they can do that with minimal amount of cost, that is a huge win. So when the government, which controls the doctors in a Nationalized Healthcare Country BTW, sees a demand for a test, which has unproven benefit and is likely to increase demand for further healthcare services: "I have a 9p21.3 SNP and now I think I have chest pain"........They look for ways to stem the tide of this cost.

Thus they expend less to keep you as healthy as physicians are scientifically capable of doing TODAY......maybe someday this testing will be clinically useful....but not yet. At least not for most of it.

In fact, I chuckled when 23andME went to Davos to woo, Europeans. Their healthcare is even more pragmatic than ours in the US. So this move by Germany is aimed at stemming costs not to make more money for doctors.......Which BTW, if everyone was acting on this SNP info, we would have a ton more procedures.....which would in the end make more money for MDs in the US.....which is why this whole, gatekeeper business is about the most ignorant argument I have ever heard......

Lastly, Medicare has opted to not pay for CYP2C9 and VKORC1 testing for warfarin dosing. I am certain you may have read about it, but here's the spin......despite having good evidence behind its benefits, it wasn't ENOUGH benefit for the US Government to pay......Despite being ENOUGH for the FDA to put it on the box.....

Do you see where I am headed? Yes, despite an article in the New England Journal saying Comparative Effectiveness Research will be a good thing for Personalized Medicine(article to come out tomorrow), we may actually have the opposite effect. At least until the costs of sequencing comes down to less than a Chest Xray.

Ah yes, everyone would like to know that they get the Maximum Benefit to Cost ratio, but sometime you just have to ask yourself..........are leeches that much cheaper than phlebotomy? That is the problem with Comparative Effectiveness when you put cost into the mix. Which is precisely what the government is paying for........Why wouldn't they? I just told you why they would be interested in this. I am interested in this. Who wouldn't be?

I guess the people who bid for the KNOME GENOME on Ebay, that's who....

The Sherpa Says: Congrats to the girls at 23andMe who managed to get listed on the same top beautiful people list an Sully. That is a PR feat, to get them listed alongside someone who actually saved lives of people in a tremendously heroic feat........I hate marketing and fluff journalism! Shame on you Tonic....You actually listed them ABOVE Sully! Maybe that's why MDV Divested from 23andME.

Like I said........

If you have been following me at this blog for any amount of time, you know that I have been a careful watcher of these GWAS studies, and the testing companies who sprung up after them.


I have been skeptical of most of these studies unless they have had replication and fairly large Odds Ratios or Relative Risks........why? We are looking for clinical relevance and asking what can we do with this to better our patients lives........

Personalized medicine relies on several things but these 3 are absolutely needed: Prediction, Prevention and Privacy. It is rich in fields like Cancer Genetics, PGx, Preconception Genetics.

You see Personalized medicine is not just Prediction, which these DTC companies are touting, it is therapies and action......which, these tests unfortunately are lacking in.....


Unlike Pharmacogenomics....

To put it bluntly.....based on our current knowledge of what these SNPs are and what they do,

Consumer Genomic Testing is of:

Extremely Limited Clinical Value


We saw this with 9p21.3 one of the most significant findings in this arena.


Yesterday an article was released in PLOS which I just linked to which states that case pretty effectively.

I often say, that once a discovery is made of a gene or SNP or etc.....it will require at minimum 5 years to come to clinical utility.....So how could any company sell something prior to this under the auspices of medicine???


The conclusion from the PLOS paper:


Our analyses and examples show that strong association, although very valuable for establishing etiological hypotheses, does not guarantee effective discrimination between cases and controls. The scientific community should be cautious to avoid overstating the value of association findings in terms of personalized medicine before their time.


Association is NOT causation, nor is it actionable.......


Most of this small time SNP data comes through in guess what????


Family History!!!!! (five exclamation points for Daniel)


The Sherpa Says: Family History is FREE!!!! And Soon SNP testing will be too.

2009, Kansas is going Bye Bye!

Ok, So last year I closed with a joke from Francis Collins, who by the way, I predict to be the next head of the NIH....

The Joke?

"There is this woman who is married to a research geneticist......... He keeps telling her how great their sex life WILL be."

That certainly was the hype from 2008. As we finally begin to wash ourselves off from the greatest hype and over-selling ever committed in Genomics, we may be a little skeptical...Even the FDA has now jumped on the regulation bandwagon. That's ok. But please don't dismiss Personalized Medicine as dead. Trust me, We've only just begun....

To prove this works.....

First, I am proud to announce that Helix Health of Connecticut is the newest member of the Personalized Medicine Coalition. In addition, I will be serving on their Clinical Science Committee. I am excited for the meeting on Feb. 12th!

Second, I look forward to developments from Coriell. I am told that their "disruptive move" by offering patients a Genome SNP scan at no cost, shook up 23andMe, encouraged Navigenics to partner with Scripps on a "similar" study and Caused Kari to Scream with fits of four letter expletives at a recent NIH/CDC conference.....

Why at no cost as opposed to the study funded by Navigenics and Scripps, which charges participants? They feel (and rightly so) that no one should ever have to pay for research which is being implemented through them. Yes, true they are non-profit. But have you ever seen BMS, Pfizer or Novartis charge patients for drug research????? It just doesn't make sense.

Coriell is at its heart a Medical Research Institute. My hope is that Helix Health of Connecticut will learn to be the same. A patient-centered genomic healthcare instutute.

We are also looking forward to several other announcements likely to come out in the month of January.

As for the rest of the field, things are progressing nicely. Some of the barriers we have discovered are finally being ascended. See, Cue4, Generation Health and another company I had done some work with.....

But, without further ado.......

Finally, what you all have been eagerly anticipating.

The Sherpa's Predictions for 2009.

Mind you they come in 3 groups. Highly likely, Possible and Ridiculous

Highly Likely:

1. Francis Collins will become the director of the NIH and collaborate with Kari from Iceland to create a national database of genomes. This is the only way to jumpstart personalized medicine. My feeling is that Kari knows how to do this, is a friend of Francis, and Obama is likely to give him the greenlight on this, despite public sentiment....

2. We will see our first lawsuit for a pharmacogenomic cause. My colleague over at ASU, Gary Marchant says it will only take one and the flood gates will open. The lawsuit will be based on something called "Loss of Chance" doctrine. The theory goes, "did you cause the patient to lose a chance at a better health outcome?" If the answer is yes, well then you can be sued. This recently has been the case for delayed diagnoses in several states (24 to be precise). All it takes is one smart, enterprising, hungry attorney to go after this....I can see it now.

Plantiff's attorney(PA) "Doctor, who is the FDA?"

Doctor(MD): "The US Food and Drug Administration"

PA "and what do they do?"

MD: "FDA provides safety information on drugs and other FDA-regulated products, and allows for adverse event reporting."

PA: "Would you use a drug that was not approved by the FDA?"

MD: "No"

PA: "Doctor, would you mind reading this label?"

MD: "…genetic variations in the CYP2C9 and VKORC1 enzymes may influence the response of the patient to warfarin.” In the “Dosage and Administration” section, it states that lower initial doses should be considered for patients with genetic variations in CYP2C9 and VKORC1."

PA: "Doctor, what is the genotype of the defendant Mr. X?"

MD: Silence....

PA: "Doctor?"

MD: "I do not know"

PA: "Doctor, why do you not know everything you need to know about a patient PRIOR to giving this deadly rat poison"

MD: Silence

PA: "Doctor, is there evidence showing that patients with poor metabolism would need a lower dose than the one you prescribed Mr. X?"

MD: "Yes, but......"

PA: "But what doctor? Why would the FDA put something on the label if there wasn't solid evidence behind it?"

PA: "furthermore, if you knew your patient had a liver problem with metabolizing the medication, would you give the dose you gave to Mr. X?"

MD: "Well, hepatic dysfunction is (cut off by attorney)

PA: "CYP2C9 genetic mutations ARE hepatic dysfunction doctor"

I think you get where I am headed. In economic lean times, people will try anything....and this sure is like the Statue of Liberty play. It WILL score a touchdown, that's why people still run it.

3. We will see George Church's Exome project results and they will certainly confuse all of us as to what it really means. We may even see a broken ladder?

Possible:

1. We will have an X-Prize winner. If PacBio and the black box known as Complete Genomics work out, this will be ready by November 2009. Seriously.....now, to sort out what the hell it means......We need a database, someone to actually take liability (Unlike the chickeSh!^ companies today), and someone to counsel on this.....do you really think 2700 people is enough???? That is only a cool 111,533 people per provider......at 2 hours per evaluation that is only 223,066 hours of work, only 9294 days of straight work, or 25 years straight!.....give me a freakin break NSGC/ABMG/ABGC/ACMG!

2. Mr. Stoicescu sues KNOME for a 345,000 USD refund. It could happen, the oligarchs lost a ton of money last year. I am sure he could use the money back in exchange for Complete Genomics Genome evaluation.

3. Oprah will have a third hoax on her hands as she discovers her genome scan was bogus. 3 strikes and your out Oprah!

Ridiculous:

1: Mark Cuban will buy the rights to 23andMe's database. If I have at least one thing, it is tenacity.....this one will happen

2: A new technology called next-next-next-next gen sequencing will debut and have your genome done in 15 minutes. They will say the technology will be ready for prime time in 2 years.

3. The United States will fracture into 6 territories controlled by Russia, Mexico, China, Canada....I think I played this game in the 1980s.

The Sherpa Says: Happy New Year! May the new year be as good for you as it already has been for me. Here's to personalized medicine in 2009!!!!!

We have no clue what it really means....Merry Christmas

The scene, a roundtable of geneticists reviewing a case.

Geneticist 1: Well, some one (Non geneticist) astutely ordered genetic testing for condition X before we saw them. When we saw them we ordered a Chromosomal Micro Array (CMA) and a karyotype....

Geneticist 2: Well, did you ate least think of condition X?

Geneticist 1: Not really, it was pretty atypical for condition X so we thought we might find something with a CMA.

Geneticist 3: You'll certainly find things with a CMA. Now what the hell you will do with those rare deletions and duplication is another topic.

Geneticist 4 and Training Geneticist 5: "Chuckle, Chuckle"

Geneticist 1: Well, while we were waiting for the CMA, we were notified by the patient's family, they have condition X....

Geneticist 2: Wow, I would have thought it was Condition Y based on your presentation which would have been picked up on CMA.....

Geneticist 1: Well, we did pick up something on CMA...

Geneticist 5: Let me guess, a rare unknown duplication

Geneticist 1: Correct, how did you know???

Training Geneticist 5: 50-50 shot.

Geneticist 2: So now what will you do.

Geneticist 1: Same thing we always do. Test mother and father, if they're "normal" we will say it is a benign event......

Training Geneticist: Too bad we can't say "We have no clue what it really means....Merry Christmas"

Close scene....

Today this is happening at an alarming rate in clinical genetics services in academic centers everywhere.....

Here's the catch.....It will only get worse before it gets better, and it will take a very long time or 10 million people to make it better.

We really have no idea what is in store when we start looking at all these genomes....My guess is that even the smartest geneticist will be rendered a bumbling idiot at least 10 times in the next decade.....

The Sherpa Says: A smart entrepreneur finds solutions to this and many other problems that wil stem from this crazy genomic data......and when Francis becomes NIH director, the US will turn into DeCode/Iceland, it is the only way to figure this stuff out.....too bad the public isn't ready for it.....Franics is no Kari and the US is no Iceland....Merry Christmas!

All people have time bombs!

I received an email from a colleague that said..."interesting.....click here."

Ok, so to anyone surfing on the internet probably not a good thing to do right? My friend likely has a virus on his cpu, right? Well, being the avid risk taker I am...I click. Guess what I find.

A blog called the Belligerati...interesting name, but the blog has argument is all wrong.

"Many will see the headline Congress Passes Bill to Bar Bias Based on Genes and be pleased.
The legislation, known as the Genetic Information Nondiscrimination Act, prohibits health insurance companies from using genetic information to deny benefits or raise premiums for individual policies. (It is already illegal to exclude individuals from a group plan because of their genetic profile.)
Employers who use genetic information to make decisions about hiring, firing or compensation could be fined as much as $300,000 for each violation.

Not me."

The blogger then goes on to detail why they think it is a bad thing. The major argument and one I have been seeing a lot of lately is based on pure fallacy and demonstrates how a very smart and educated person can be completely illiterate in genetics and genomics. I would say that about 10% of the population understands genetic risk when explained to them....that's about it.

From the blog:

There are many forms of luck in our society that we allow people to capitalize upon. For example, citizens keep the majority of the returns from wealthier parents, natural talents, being born into a rich and free society, their appearance, and temperament. Yet congress has passed a law that says that people may not capitalize upon their generic luck. This makes us less free, and ultimately less wealthy as well.

Genetics as luck....interesting. Perhaps they don't know that most heritable genetic changes are for the bad. Mistaken concept 1, in addition, Genotype + Environment = Phenome.

What sense of justice legitimizes forcing those who are poor but blessed with rich genetic endowment of healthy genes subsidize those that are middle class and endowed with a genetic propensity for several diseases? As I have said before on this blog, the way (the just way, if any) to address the suffering in our society is to give money to the poor. These back door methods, like this genetic non-discrimination rule, are often more unfair then the ills they prevent

This is super Bass-Ackwards. What sense of justice forces those with no control of their poor genetic make up to be excluded from health insurance....Man...this blogger is crazy.

His argument is that by genetic testing we should benefit from our "protective genetic make-up" and that GINA will prevent us from doing this.....

The second concept I want to clear up for everyone is this. "We can test for healthy genetic variation".....Let's get this straight. We know very little about the genes in our bodies that are protecting us from crappy environment. Eric Topol talks about this. For a cardiologist, this guy has done a great job of becoming a genetics Hacker! He says we should study the healthy, not the ill. I think he is right.

The third concept......we understand what genetic changes cause common disease. Let's get a clue. We know that several genetic changes have been weakly linked to (to be read as associated, not causative) common diseases. We also know of some very strong monogenic links to diseases like cancer and heart disease. But these are not the most common.

Francis Collins says "Everyone has at least 5 or 6 genetic time bombs in their genomes"
From the guy who headed the HGP....I'll take it at face value. We will only know this for sure by doing whole genome scans on everyone. By whole genome, I don't mean these chips that "claim to be whole genome" I mean, base by base, methylation by methylation, histone change by histone change, genome sequencing.

So if that is the case....why should insurers test for something that no one knows is a risk or protective allele. To them, it makes no sense to have meaningless data. But to have accurate tests for actuarial evaluation. That would be most worthwhile. My guess is that if they were to use this unvalidated and suspect data that everyone would be getting higher rates. So this argument from the Belligerati demonstrates the lack of genetic knowledge even in the most sophisticated and educated public.

There are other arguments against GINA. But I say, right now it is the best start we have at protecting our citizenry.

"GINA is the first major new civil rights bill of the new century," said Senator Edward Kennedy (D-MA), who cosponsored GINA in the Senate with Senator Olympia Snowe (R-ME). "Discrimination in health insurance and the fear of potential discrimination threaten both society's ability to use new genetic technologies to improve human health and the ability to conduct the very research we need to understand, treat, and prevent genetic disease," said Kennedy

I agree wholeheartedly. With so many people having at risk alleles.....in these SNP studies at least 1 % of the population has to carry these SNPs....That means 3 million people at a minimum are at risk of one thing or another. Genetic Discirimination is the new racism.....I hope not to see its ugly head rear for a very long time.

The Sherpa Says:
Confusion and misinformation can lead to making poor choices. That is why I advocate for education and guidance in the field of genomic medicine. How can we expect even the most sophisticated population to understand this on their own? It tooks me years of study to be where I am. And I learn something new every day! That's why we are going to launch a brand new wave of education and service shortly......

ABC, Misinformation and Government Regulation

I have to comment on something. ABC news tonight covered the whole drama in California.....But they really didn't. In fact they gave 20 seconds (approx) to the fact that the government was finally regulating this industry....they did even manage to squeeze in that the FTC is investigating deceptive advertising.

What the piece really was.......A human interest story....much like the excellent work done by Amy Harmon at the NYT....Which reminds me....did anyone see Kathy Hudson throw the Federal Gov't under the bus???? She now really has put them on notice and put their backs slammed against the wall.

So the ABC report?

52 year old woman caring for her mother with Alzheimers.

The pitch

"I am taking an at home test to find out what my risk for Alzhemier's"

Whoa!!!!! No one....I mean no one mentions the limitations of the test she used from....You Guessed it AlzMirror!!!! ApoE e4 testing.

In fact George says "Some tests show increased risk for a disease, then you can do something about it" The problem....they then freakin show a guy getting a colonoscopy....That is not even a close comparison

To even implicate that Alzhemiers and ApoE e4 might have the same screening and prevention as hereditary colorectal cancer is preposterous. And you wonder why the government is stepping in???? The press just made the public link the two!

Hey ABC, Next time you cover this, give the Sherpa a call!

Instead of the Sherpa....ABC picks Francis.....a wise choice....I would have jumped down the journalists throats...

I think the Good Dr Collins even quotes me.........."Genetic Snake Oil" or the other few people who used this term last year....

But, they only put Francis on for 30 freakin seconds!!!! Are you kidding me? Elissa Levin gets more screen time than him. In addition, Elissa sits down and goes over results IN PERSON on the show......Do they do that for people who test (Sorry, they don't test, they do analysis of their Non-Medical DNA data that includes risks of medical conditions) with Navigenics? I did notice, 23andMe weren't in the report....

Their participation was really minimal.....as I said this was a human interest story. What really got me was when this poor lady got her AlzMirror test results....

She said "This is great. I only have a 30% chance of getting Alzheimer's Disease"

This is the biggest crock out there! An negative ApoE e4 test is not definitive. The public now thinks that the DTC test can indicate risk of ALL Alzheimer's Disease...I am so blown away about this....Can you imagine???? Alzhemiers genetics is so confusing. There are reams and reams of data out there indicating family risk of Alzheimer's disease....It's heritability is something like 70-85%.

What was amazing, there is absolutely no commentary on the limitations of the ApoE e4 testing and the other genetics of Alzheimer's....Did they bother calling Rudy Tanzi???

I am so upset by this. That's why I am blogging.

So the real story

"But Collins says customers are getting predictions, not necessarily medical recommendations or prescriptions about what to do about the information. "

30 Percent huh?

Holly Hagy, 51, of New Haven, Conn you could have seen the geneticists at Yale.

Here are your real stats.......

1. One first degree relative with Alzhemier's disease? 500 fold increased risk......despite ApoE e4 status....Not 30% My God!!!

2. ApoE e4 is only one risk factor and is modified by other genes, there are other factors

3. Even the REVEAL study gave numerical estimates of risk based on FAMILY HISTORY!!!

4. Did you see the GWAS on Alzheimer's?

5. What about her blood pressure, LDL, stroke history....all of these things play a role.....too bad AlzMirror didn't tell her that!

6. Who can she sue for the malpractice she just received...No accountability by these guys.....that's another reason to involve healthcare!!!

Should ABC be pilloried on this one? I don't think so, but they should have vetted the risk prediction.

Because of this recent study!

"The pilot study showed that there was limited knowledge of genetics overall and AD genetics in particular, considerable concern about personal risk, and little knowledge of or interest in genetic testing for the disease."

ABC just increased interest and actually portrayed incorrect knowledge....way to go! And you wonder why the government is getting involved in DTC testing????

Smart Genetics got a letter.....Maybe ABC should too? JK

Ms. Hagy, please give us a call and we can put your ApoE e4 results into the proper context!

The Sherpa Says:

This is precisely why the government is stepping in guys....they can't allow the press to butcher it AND Hype it.........the companies to tell less than half the story and hype their tests..........the consumer to be duped into false statistics..............and Kathy Hudson to point out that the federal government has been asleep at the switch for the last 30 years......This is only gonna inspire more regulations....Or at least enforcement of the ones that exist......adjust it for new technology? Last time I checked, genetic tests have been around for over 2 decades.....

A$$ Kicking

Whoah! I never thought that my blog would generate such response! I received over 100 emails today. Guess what. In a near 50/50 split they were pro or anti regulation. Some were so nasty and hate filled I began to question why I was even blogging about this. Luckily, none threatened my pets or family! They even asked me whose side I was on. I think I have been pretty clear on this one. I am on the side of safe and effective personalized medicine. That's the only side to be on. I am FOR the Genomic Medicine revolution. I am against anything that will hinder its' development. Some of these fly by night companies have been doing just that for years now!

So I must sit back and look over the landscape. I knew this is where we were headed. Maybe we need a refresher course in history to understand why it did not start with 23andME, they were merely the straw that broke the camel's back.

1994

-Scientists isolate BRCA-1 Including my new friend Ken Offit

-JAMA publishes article on the psychological harm of genetic testing

-The Human Genome Project is in year 1

-The UN Draft articles stating:
Article 17 (Tests predictive of genetic disease)
Tests which are predictive of genetic diseases or that may identify a genetic
predisposition to a disease may only be performed for health purposes or for scientific
research linked to health purposes.

-The LA Times asks "Can We Know Too Much?"

-O.J. Simpson trial involved Genetic Testing

The results? Genetic testing is risky....

1995

-Enter Francis Collins Testimony to Senate Including him not endorsing BRCA testing YET! Awaiting further study validation!!!

-GINA is introduced in congress by Louise Slaughter, she heard what Francis had to say. Further validating the risks in genetic testing.

-The government creates TFGT, out of the Human Genome Project

1996

-ApoE testing is now commercially available, despite limitations in predictive capabilities.

-The New England Journal of Medicine validates the risks of genetic testing

Worried patients, encouraged by overly optimistic claims by researchers, biotechnology companies, and the media, may want to have genetic tests performed whose validity has not been established.

Truly Prescient!

1997

-NY Times exposes doctors shortcomings in interpreting Genetic Tests! Unfortunately, little has changed.

-Francis goes back to the Hill.

-NIH encourages CF screening for pregnant women.

-GATTACA Debuts! 4.3 million dollar weekend. The review? Older children with a taste for science fiction should find it intriguing.

-The Seattle Times cries for regulation of this fledgling industry. It's coming....in 11 years

-The European Convention on Human Rights and Biomedicine” convenes and article 12 states

Tests which are predictive of genetic diseases or which serve either to identify the subject as a carrier of a gene responsible for a disease or to detect a genetic predisposition susceptibility to a disease may be performed only for health purposes or for scientific research linked to health purposes, and subject to appropriate genetic counselling.”

1998

-President creates SACGT, The Secretary's Advisory Committee on Genetic Testing (Let the regs begin!!!)

So I am done doing blow by blow....

2001

-Psychiatric issues of Bad Results reinforced

-American College of Obstetrics and Gynecology endorses CF carrier screening for all pregnant women. Making carrier screening "Standard Medical Care"

2002

-Gene Watch UK advocates for regulations of nutrigenomic testing and bogus tests

-First Insurer to encourage coverage for genetic testing, AETNA. Too bad they don't pay for the counseling (Yet)

-JAMA sounds off on DTC genetic testing. Of Myriad

-UK and the BBC expose the bogus testing industry. And push for regulations.

-Despite all GI doctors taking family history only 30% knew there was genetic testing for Lynch Syndrome....sad

-Australian Medical Association reinforces genetic counseling with testing.

2003

-Ryan Phelan enters the field, with DNA Direct

-SACGHS is formed. It is much more expansive than just reviewing testing

-CLIA is needed for testing.

-The FDA says it needs fangs.. Asking the gov't for these teeth!

2004

-Amy Harmon (Now Pulitzer Prize winner) Starts covering the topic with DNA Age

-EU met and issued 25 recommendations regarding genetic testing INCLUDING Rec 8
the appropriate medical environment for providing information prior to
testing and relevant post-test counselling be in place prior to offering such
screening

-CDC holds their first short course on this genetic testing.

2005

-HFE testing for iron overload is doubted in NEJM. ONLY 20-30% of those with HFE genes develop Hemochromatosis. Genes aren't everything!

-Pew Trusts calls on stronger regulation by CMS. CLIA Complies

2006

-DNA Direct speaks at SACGHS, they are further convinced of the need for regulations.

-Kathy Hudson's group accuse the Federal Government of Neglect in regulations. Their back is now offically against the wall.

-The Genetic Alliance jumps on them too!

Ok, Maybe Not Done with Blow by Blow......

2007
-The Sherpa Starts Blogging! Day Zero for the blog. Year 13 for the Sherpa!

Who in their right mind would open genetic testing companies in this environment?

-Reykjavik Does....wisely avoiding the CLIA trap!

-BOOM! Google does too!

-Helix Health of Connecticut starts, quietly.

2008

-The following bogus DTC tests are available: Hair Loss, Sexual Mate, Bipolar Disorder I won't go on.

-Dept of Health and Human Services weighs in. With 276 pages Is that enough writing on the wall?

-Not enough, Navigenics then Launches. Party in SoHo anyone? Although the leak was evident in 2007

-NYS investigates and warns the "Big 3"

-CA sends cease and desist letters

Failure to regulate your own industry only gets you governmental regulation. Failure to investigate the past dooms you to the mistakes made in the past. I am still blown away about the lack of consideration for what the government can do and will do.

The Sherpa Says:

Since I got my a$$ kicked by some of my wonderful readers. I reassert. I am on the side of the Genomic Medicine Revolution. In the most ethical, responsible and effective way possible. End Of Story. I am about "Do What's Right!" My father taught me that a long time ago. Now you just saw what I see. That'll be 20k please ;)

New England Journal, Prostate Cancer and Babel

Remember when I said that all of these association studies had weak Odds Ratios? I also said in the Sherpa's golden rules of genome wide association study that any OR less than 2 is probably not better than a family history. Here we have a study in the NEJM listing a powerful combination of SNP data AND Family History. This was e-published back in January, but I draw your attention to it again as it deserves notice.

In a significant meta analysis it is shown that the OR if you have a first degree relative with prostate cancer is 2.5 I hope Genome-Boy and his trusty side kick Prosty are reading!

Well, this study and its shortcomings...There are some. This study Blows mere family history out of the water. This study, dubbed CAPS, evaluated Prostate Cancer in Sweden.

The analysis of SNPs revealed 5 SNPs which had significant risk implicated...Here's the kicker, if a person has 4 SNPs and Family History, then your Odds Ratio for Having Prostate Cancer is.....get this 9.46 compared to the men who had none of these factors.

Take That PSA and Digital Rectal Exam!

Now where does this study have shortcomings?

1. It is retrospective and this is subject to bias, therefore needing prospective analysis before we will use it.

2. This population is a relatively homogeneous population that breeds nationally

3. Only one of the SNPs has an identifiable gene. Without a gene, we can only guess what role the SNP may play let alone devise a medication or treatment to offset these effects

The Sherpa Says:
This is what I am talking about! When replicated prospectively...and this will be, this will be a powerful tool to use for risk stratification. To my journalistic friends, please don't report the Odds Ratio as if it were a relative risk! To my prostate prone friends....cheer up. Prostate Cancer is rarely a killer.

Garbage In, Gospel Out

There is an old saying called "Garbage In, Garbage Out" This saying was coined by George Fuechsel an IBM hack. Other such terms like FUBAR, SNAFU, and even KIBO reflect some of the issues we have going on with personalized medicine and even medicine as a whole.

This term is especially poignant today when the Wall Street Journal casts a shadow on the field of pathology and personalized medicine testing for breast cancers. The drug Herceptin is one of the Vanguards of what I called personalized molecular medicine therapy.

You see, Herceptin therapy is targeted towards a certain type of breast cancer. In this type of breast cancer your cells have a protein located on them that can encourage cells to grow. When this protein is blocked, cells die. Therefore, Cancer is beaten back. The catch, if you don't have this protein in your cancer, you don't respond to Herceptin.

This is the paradigm for personalized medicine. We test your cancer to see if it has this molecule. If it does great we give you Herceptin. If it doesn't, too bad, it's regular chemo for you. But what happens when GIGO takes over? What if the tumor sample is bad? What if the lab analysis is bad? What happens when the lab technicians are inexperienced? Garbage In...

So what do you get? Patients on Herceptin who may have not benefited from this therapy and perhaps would have benefited from the standard treatments. Simply because their test results were reported as positive. Even if this report was a mistake. You see, doctors got caught up in the worst acronym of all "Garbage In, Gospel Out" This term was coined to essential remind us how we often treat computer output as infallible. This is the very same case in medicine with pathology laboratories. I often go to the lab myself to double check results. Time consuming? Yes. Life saving? Absolutely!

The Sherpa Says:

What happens if the same thing occurs with whole genome analysis? Last time I checked, Copy Number Variation, Non-coding sequence, "Dark Matter" are all part of our genomes. Do we have a good handle on how well we can sequence this stuff? More importantly, we must not let genomes become Garbage In, Gospel Out"

2008 Here We Come!!!

After some time off thinking about where Personalized Medicine has been headed and where it could go I have come up with some simple conclusions. But first I want refer all of you to my interview with Bertalan Mesko over at ScienceRoll. Bertalan will be headed over to the US and working with me to educate physicians on Medicine 2.0

Why do I refer you to the interview? Because I breakdown molecularly personalized medical services into several categories. There is much confusion as to the term Personalized Medicine. In fact, Helix Health of Connecticut's marketing team has told us based upon their research that some even mistake this field for concierge medicine!!

This article recently released in the New England Journal of Medicine speaks for what I called Personalized Genetics. For those of you who don't know, in 2006 the nobel prize in medicine and physiology was awarded for the discovery of RNA regulation of protein synthesis. This study is a neat expression of this unique technology. By identifying patients with a "Genetic Disorder" (What disease isn't genetic?) researchers have created a new piece of nucleic acid that will actually tell the machinery in the cell to do something other than it was coded to do.

Say Wha? Ok. Muscular Dystrophy is caused by absence of a certain protein called Dystrophin. If muscle cells can't make this protein, then they cannot function. Children often are wheelchair bound before 10. Why can't they make the protein? Usually, the gene which codes for the protein is defective. Its defect causes the gene to protein machinery to stop making the protein very early in its production. This results in a non-functioning protein. This new product PRO051 tells the machinery to pay no attention to the defect. Instead the machinery keeps going and creates a semi-functional protein.

So why is this Personalized? Well, not all people with Duchenne's have the defect required for this medicine to work. But unlike with Lipitor where the therapeutic success rate is anywhere between 40-50%, PRO051 will be effective in approximately 70% of people. Why? 70% of persons with Muscular Dystrophy have the needed mutation. In people with high cholesterol there are multiple different genetic changes as well as environment. But imagine when we can say "You have high cholesterol because of these genes and this environmental exposure. We will cut out this exposure and tweak these genes just a little bit." Voila, No more Lipitor!

Personalized Genetics could become Personalized Medicine...but not yet. I think this author from the NEJM has read my interview too..

"Personalized molecular medicine." As with other catchy terms for big ideas, such as "reversing global warming" and "renewable energy," the concept of personalized molecular medicine is certainly important, but the path to achieving it is far from clear. When such phrases are considered, definitions are important.

Does personalized molecular medicine mean the tailoring of drugs for the individual patient, an approach that evokes images of Bones on Star Trek making instantaneous diagnoses with his Tricorder followed by loud pneumatic injections of customized drugs? Such a concept would place the realization of this technology in the same time frame as the achievement of "warp drive" that hurtled the Enterprise into new galaxies.
On the contrary, personalized molecular medicine appears to be at our doorstep.

Unfortunately, I don't think Dr. Hoffman is aware of Helix Health of Connecticut. Personalized Medicine is at your doorstep too.....

The Sherpa Says: The conclusions are coming. I think Yoda said it best "Patience" This year will require tremendous amounts of it. Francis Collins tells a joke "There is this woman who is married to a research geneticist. He keeps telling her how great their sex life WILL be." Thank you to a certain unnamed TV news series for thinking of me when covering Personal Genomics. I look forward to our discussions. Does anyone think the New Year's Ball looks like an AAV?