Personal Genomes in Clinical Care. Quake paper Falls Short!

With all due respect to the scientists involved in analyzing Stephen Quake's genome in clinical context.

You did a major league $h!tty job.

No offense.

I can only assume this based on what you reported in the lancet paper.

Start by asking yourself.

"Is Stephen healthier because of what that genome and clinical assessment added to his care?"

I am speaking precisely on this topic at the Consumer Genomics Conference on June 3rd at 830 AM. So I will hold off on all my arguments....But,

The Paper even says

"We noted that most of the sequence information is difficult to interpret, and discussed error rates"

Ummm, ok. Nice counseling session.

"patients with whole genome sequence data need information about more diseases with a wide clinical range"

Perhaps that person could actually be a physician, maybe a generalist?

"For this we offered extended access to clinical geneticists, genetic counsellors and clinical lab directors"

Nice! Joubert's is not Gilbert's is not Plavix. Thanks for stopping by.

I did appreciate that your paper calculated pretest probabilities. Unfortunately these were based on a pedigree which had no ethnicity and incomplete clinical data.

1. No Glycohemoglobin to evaluate for diabetes risk or maybe even diagnose it
2. No Iron Studies to evaluate for Hemochromatosis, yet you state genes may set him up for it.
3. No documentation of a physical exam including DRE for prostate hypertrophy/cancer or PSA
4. No dietary history? No Smoking history? No social history?

Shall I go on?

You show increased risk for Diabetes post test as well as prostate cancer, obesity, CAD, MI, Asthma, NHL, RA (no ESR/CRP/CCP?)

You projected an increased risk for 7 and decreased for 8. Yet no Assessment of MCI etc in Alzhemiers disease? My god, you did a stress test in an asymptomatic patient who exercises daily.

"Although the methods we used are nascent, the results provide proof of principle that clinically meaningful information can be derived about disease and response to drugs in patients with whole genome sequence data"

Translated: We made up a system and used novel DNA results to hypothesize about disease risk using research fellows, computer programs an excellent cardiologist (Not a GP) and an Echo machine.......But we skimped on the physical exam, use of primary care doctors, complete blood counts and other clinically useful testing and procedures.

I admire your efforts, but

A. You have missed the boat in using not all the tools at hand
B. By being Genome-centric, we miss the clinical picture.

"Although no methods exist for statistical integration of such conditionally dependent risks, interpretation in the context of the causal circuit diagram allows assessment of the combined effect of environmental and genetic risk for EVERY individual"

Translation: Nothing exists statistically to evaluate disease interaction and how it may increase risks of interlinked disease.

Ask yourself, "What have we done to make Stephen Quake healthier from this test?". Other than hype the use of a genome clinically?

This paper was all genome and NO CLINICAL ASSESSMENT!

The Sherpa Says: The only thing of note that is important here is the CYP2C19 data.......
I have seen abnormal CGH data in a child with severe developmental delay come directly from a high functioning mother who was a power litigator. The genome scan as it stands now is noise. It also requires a full team a month to intepret. Clearly not ready for medical prevention or prognostication, sorry.

Celexa Strikes Home

I have been working most of the night. I think it is funny how when you open your eyes to something, then you begin to see it all the time.

A great example is the Fed Ex logo. I dare you to find the hidden symbol....I'll even tell you the symbol....It's an arrow.

Keep trying.......

Didn't get it? Think a White Arrow....

Ah Ha!!! You got it. Now everytime you see the logo you will be looking for the Arrow!!

Tonight I admitted a great patient who attempted suicide. Interestingly, the patient had just started citalopram (Celexa) therapy. I almost feel as if the blogpost and literature review had me attuned to what was going on.

I spoke with the family and with the physicians. I am amazed as to how often these occurences are. I know that we will soon have an FDA approved test for this risk. I just feel bad that it had to be too late for this patient.

We are giving people too many medications without evaluating them. We are giving too many medications without knowing exactly what the risks are. Frankly, I am surprised this push for drug safety and pharmacogenomics has not started sooner.

I think it is because as physicians we too easily blow something off as idiosyncratic. There is not enough intellectual curiosity going on in medicine. Primarily because we are all overworked, secondarily because most don't have the proper molecular background to evaluate and understand the issues which we see. This is not the fault of physicians primarily. I blame their teachers........

The Sherpa Says: For a public who thinks everything is genetics and a set of healthcare providers who think it is not genetic in adults we have a disconnect. Even worse, we have a failure to communicate. Which is why companies like Navigenics et.al. come to be. They want a scalable solution to our education problem. By cutting out those who are "educated" How does that play out? We will soon see. The good news is, the physicians who I educated tonight asked if we could send the test. The bad news is "I think it's too late" at least for her. She does have a sister though.

Sherpa quoted on About.com

Today I was just informed that I had been quoted on About.com, Dr Glenn Gandelman is an excellent cardiologist working in Greenwich, Connecticut and in New York City. More importantly, he is the lead author of HeartAttacks.about.com.
From the article

"Who can help me obtain a thorough family history?
A basic family history is part of a complete physical examination and should be updated on a yearly basis. It's also a good idea to let your doctor know of any new illness that occurs in your family. In some cases more specialized genetic counseling is required. Your doctor may refer you to a geneticist in such cases. According to Dr. Steven Murphy, a physician with Helix Health of Connecticut, “there are specialists in medicine such as geneticists and genetic counselors who are trained to take and interpret family histories.”

The Sherpa Says: This site is an excellent resource for cardiovascular health and information. Make sure you check it out often.

Scientists and The Sherpa Urge Caution

According to a recent post at Medical News Today a new article will be published in Science urging caution with the availability of genomic sequencing. I have commented on it several times and now feel like we are beating a dead horse.

Listen, if you want your genome to help you decide what clothes to wear, or perfume, or as a trophy. Then go out and get one. I will never stop you from getting your genome as a novelty. But if you want to use your WHOLE genome to make healthcare decisions.......... Well, you better get a second opinion. The only genetic testing that will work for healthcare has nothing to do with whole genome analysis.......for now. So why get your genome? Because, if you get it once you never have to do it again? Well, you saw how that worked out for the iPHONE right?

On a lighter note, as I sit here in the ICU taking care of really sick people I am left to think....What if we could prevent chronic diseases? These are the diseases which once end-stage put you in the ICU. Where I now sit taking care of end stage heart and kidney disease. That is where the power of the genome lies.....in prevention.

The Sherpa Says: Early adopters are wonderful. The world would not advance if it weren't for those who challenged conventional wisdom. But when it comes to human life........well, I am not ready to "crack a few eggs"