Sir Hillary? What about Norgay?

It is with great sadness that I speak of Sir Edmund Hillary's death. I have always respected this man. He Climbed to the Zenith of Mt Everest. He did what few dared to do. He saw conventional wisdom and he laughed in its face. But what was great about Sir Edmund was not that he climbed the mountain. No, No. What made him great was that he climbed down the mountain, giving back to his people, caring for the people of Nepal: setting up schools, educating the locals, raising the standard of living for those who helped him the most.

While I was covering the NEJM article on Friday, Sir Edmund passed away. He was most noted for climbing Everest and reaching the zenith 7 times. More than any other non-Sherpa. Hillary loved his Sherpas so much that he went to Nepal more than 120 times. He set up hospitals, health clinics, airfields and schools.

The reason he loved his Sherpas was simply because he knew how good hearted and caring they were as a people.

I feel that Sir Edmund and Tenzing Norgay's relationship is an analogy for Medicine and the Gene Sherpas all over the world. The feat to climb the mountain known as personalized medicine with its lofty goals of genetic and genomic health for everyone will require just as much planning and care and partnership. Once we get to the top (Yes a true feat) the work is not finished, we must plan for what the next steps will be. We must give back to those who got us there. We must give to those who will get us there again hopefully 6 more times.

The Sherpa Says:

We must be prepared to educate, to heal, to build infrastructure, and to dedicate our lives to nurturing this dream known as Genomic Healthcare/Personalized Medicine. You see, our job as Sherpas is to get Medicine to that dream. But our job doesn't stop there! Many Thanks to Jonathan Freed for reminding me of this everyday.

Navigenics? Who was that?

So after the New England Journal of Medicine has given Personal Genome Sequencing the thumbs down, I ask you...."What will happen to these personal genome companies?"

I have several ideas....

1. They all morph into non-health related information tools. Every bell and whistle that can be marketed that will not face the scrutiny of physicians will come out of the wood works.

2. They will begin to say "The medical field has no sense of what the promise of genomic medicine is" They will attack physicians' lack of genomic knowledge. This is the tactic which nutraceutical companies use. The 'Ol "We have a secret....most physicians don't know or won't share......because they want you to have disease"

3. They will disappear, like the dinosaurs. A neat phenomenon that gave us something to write about for 4 months. Somehow I don't think Google will let that happen. But hey, ya never know.

4. They all will say "Not to be Used to Diagnose or Treat Disease" EVEN NAVIGENICS!!!

5. A new tool that uses evidence based SNP testing to identify risk will come out of the woodwork and crush them all.

6. They will create dating services around their genome scans. "Find out your perfect mate" "Discover the person who you will have super children with"

7. They will contract the Sherpa, buy Helix Health of Connecticut and it's model. Enabling the spread of directed genetic testing and personalized medicine.

8. DNA Direct and direct to consumer targeted testing will begin to partner with traditional models of genetic and genomic healthcare. They will create a more useful alternative to Genome Scanning, leaving Kleiner & Perkins smoldering for not consulting us first.

9. They will keep on, keeping on. Hoping that the limited scans which they now offer will appeal to those persons who bought a space flight, those who bought the cereal box sized mobile phone, or even those who bought Betamax

The Sherpa Says:

We must remember that Genomic and Genetic Health has nothing to do with these companies and everything to do with Personalized Medicine. My concern is that physicians will now be given a free ticket to blow of genetics and genomic healthcare. It is easy for the ignorant to not know what they are missing.

As the NEJM article says "For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets." Detailed patient reports are in the skill sets of my physicians.

The Gene Genie Gone Awry?

In an article entitled "Letting the Genome out of the Bottle — Will We Get Our Wish?" in the New England Journal of Medicine, I am left questioning if Drs Khoury and Drazen read the Sherpa. Well, I read Hsien's blog, so why can't they read mine?

These are several themes that I have been raising about Genome Scans and have even spoken with several news reporters and journalists about.

From the Article:

It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was "not a clinical service to be used as the basis for making medical decisions," he is in the office for some "medical direction." What should you do?

My first answer is to call Helix Health of Connecticut or your friendly neighborhood geneticist. My second answer is what will most physicians say? My guess is, "This is just a fad. This information is useless" They may be correct and they may not be. But until this data is reviewed by someone who is in the loop about genomic discovery, I am not so sure they can say for certain.

The next part of the article really had me thinking that they have read several of my posts.

It is likely that sample-handling errors are a greater threat to the validity of results than are genotypic misclassification errors. Yet even very small error rates per SNP, magnified across the genome, can result in hundreds of misclassified variants for any individual patient. Without transparent quality-control monitoring and proficiency testing, the real-world performance of these platforms is uncertain.

This is a significant issue. In a Journal of the American Medical Association in 2006 a group mathematically estimated that there would be a significantly high rate of false positives.

This is the problem I see with whole genome analysis for medicine. Just because we can do it, doesn't make it medicine.

But more important than any of this is the educational shortcoming that most physicians have with this data. As indicated by the authors.

For the patient who appears with a genome map and printouts of risk estimates in hand, a general statement about the poor sensitivity and positive predictive value of such results is appropriate, but a detailed consumer report may be beyond most physicians' skill sets.

The Sherpa Says:

This is why I started the Sherpa. We must stay on the Path To Personalized Medicine. Right now, Genome scans are a dangerous shortcut. Steer Clear.

To My Colleagues: If you have one of these scans from a patient, please give us a call

To My Early Adopters: Genome scans cannot be used for medicine yet, but they can be useful for other things...

To My Detractors: I am sorry if you are upset, but I will only speak my opinion.

I saw the Future!

Over the last month I have been privy to the future. Let me tell you it is not pretty. At a local hospital we have seen a dramatic spike in patients. Normally we see this spike every year. But this time it is worse. We have so many sick patients that we have had to put patients on life support on the normal floors (Nursing ratios of 1nurse:6patients) instead of the ICUs (nursing ratios of 1:2)

What is going on? It is the future, and it is inevitable. The last phase of "America's Greatest Generation" is now succumbing to the wounds of chronic disease. Emphysema, Heart Failure, Kidney Failure, Metastatic Cancer. You can only live so long. More importantly, we have been able to keep you alive much longer than if we were living in the 1960s or even the 1980s.

The future is here. This economic and medical strain of this critical care will break the system. How can we fix it? We can prevent the chronic diseases. How do we do that? We act before the disease has time to damage us. We use molecular detection, we take family histories, we use genetic screening. But who would pay for that? Smart consumers, that's who.

By identifying risk, we can reduce behaviors that kill us. How do we do this? We won't be able to under the current system of episodic care. We need a paradigm shift!

The Sherpa Says:
Personalized Medicine is that paradigm shift! Prediction, Prevention, Privacy is what is needed here. I have seen the future. We can change it, but first we must suffer from the effects of our unwillingness to change.

Watching the Debates

Tonight I take a night off of genetics posting to watch the debates. What I can't get over is that the debates are being sponsored by Facebook. Have these presidential debates always been sponsored?

If so, then have they always been marketed like a bowl game?

Will they continue to be?

The Sherpa Says:
My gosh..... I hope these politicos are ready to start "Juicing"

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?