Saturday, July 19, 2008

Reason to Love George Church and Michael Crichton

Did anyone get to see George Church's love article in Wired. I am at a point here where I begin to truly appreciate what he is doing. This article gave me some insight. You fight and fight with people about this....I think he has some merit. I think that the algorithms to assess family history risk should be open source.....I think the computational side should absolutely be free. Do I think that it could be open source....yes. Do I think that VC want it open source?

No. But it would be grand if it were. As for the data-mining as open source.....well, perhaps George still is 20 years ahead of his time. People are too afraid for this part. That is why I think getting 100,000 people without offering them healthcare could be tricky. Getting 100k without HIPAA could be tricky too. But unlike the commercial efforts, I admire George for getting Harvard's IRB review. Now what he needs is an ICOB like the Coriell Personalized Medicine Project.

Here's what I envision......NEXT.....did anyone read that book?

In the Author’s Note, Crichton comments on some serious issues.
1. Stop patenting genes. This may never happen fully

2. Establish clear guidelines for the use of human tissues.
3. Pass laws to ensure that data about gene testing is made public. Meaning results of gene therapy trials.

4. Avoid bans on research.
5. Rescind the
Bayh-Dole Act (that allows universities to patent and make money off their research).

I am reminded of this as George's lab is creating stem cells from the fibroblasts in each participant's skin cells. This could be very attractive for each participant, but I am brought back to the opening scene of NEXT when in that scene a postdoc is running to commit corporate espionage by trading some stem cells that were developed in a University lab for a bundle of cash. Only to be done in by a Russian Prostitute and some Nitrogen.

Another story gets me,
The tale of a man who carries a gene that is apparently no longer his own property, having been patented by a biotech company in an extension of eminent domain that boggles the mind. But not when put in the light of the PGP and Dr Church. George would have this gene as open source.....a nice idea. But what about when the Harvard endowment rears its ugly head??? Who gets that stuff then?

“Next” draws upon a courtroom case in which U.C.L.A. was accused of covertly using tissue from a leukemia patient to develop and patent a lucrative cell line; the court ruled that the man had no property rights to his discarded tissue, and that the university, as a government institution, could claim this material under the doctrine of eminent domain.

I have fallen in appreciation with Dr Church again. After fighting with Jason at Personal Genome, I never thought I would. But after reading the Wired article I have all over again. Why? Because when he fell in love with code at 9, I fell in love with DNA at 8. That's all it took.

You go George! I love the opening pic, too bad you are on the back pages of Wired. I would have had you lead instead of that beautifully vapid(maybe not so vapid) Julia Allison. But I am certain she pulls off the high heels better than Dr Church would.

Tomorrow, I will cover
Tony Snow and colon cancer..... If his PMD didn't test him for HNPCC, it wouldn't be a surprise. But it would be a huge miss.......

The Sherpa Says:
We are entering the NEXT phase of genetics and genomics, SNP testing was only the beginning. There are many more things we will discover and many more things that will have even greater clinical applicability. George is helping ramp that up. Me Too......


Matt Mealiffe, M.D. said...

Steve- It's well documented that Tony Snow had ulcerative colitis, a strong risk factor for colorectal cancer. Thus, unless there are additional unusual features of the family history that I am not aware of, testing Mr. Snow for HNPCC would not have been appropriate.

Matt Mealiffe, M.D.

Steve Murphy MD said...

I know about the UC. But did you know about the mother under 40 who had died of colorectal cancer??


MSI and IHC are in order, for the sake of the rest of his family.

Matt Mealiffe, M.D. said...


I disagree.

I was indeed aware that Tony Snow's mother died at an early age of colon cancer.

As for Mr. Snow, he had UC for close to 3 decades by the time of his colon cancer diagnosis. At ~30 years out, the risk of colon cancer without prophylactic colectomy is pretty impressive. Thus, it's not necessary to invoke any additional diagnoses to explain his colon cancer.

As for his mother, there are several possibilities. Given that there is a role for genetics in UC, it is quite possible that she may have had UC-associated colon cancer as well.

Can I rule out the possibility that she may have had a Mendelian colon cancer predisposition syndrome? The answer is no, just as it is for anybody I just see walking down the street. However, as Mr. Snow's cancer can easily be explained by his UC-and as screening everyone walking down the street for HNPCC is not something we do, a reasonable approach would be further investigation of Mr. Snow's mother's medical history (including the pathology report, the location within the colon (i.e., was it a right-sided cancer), and whether there was any evidence of substantial colonic polyposis. An astute physician with access to this information can make a reasonable decision regarding whether it was likely to be UC-associated, related to a polyposis syndrome or plausibly related to HNPCC and therefore worth considering further testing(regardless of Bethesda criteria, etc).

This would be a much more reasonable approach than announcing to the world that the lack of testing for HNPCC in Tony Snow was a "huge miss" on the part of Mr. Snow's primary care physician and other care providers.

Matt Mealiffe, M.D.

Steve Murphy MD said...

I too am aware of the pathologic findings making it "More Likely" to be UC related. UC and all IBD does have a genetic component.

In order for both family members to not be a single gene...In my mind here is the scenario.

Mom would have to have any combination of the 30+ genes associated with UC, have UC at such a young age as to die from a colorectal cancer component at 38 YEARS of Age.

THEN prior to death she would have to pass on to her son, the same or similar cadre of genes. To which her son would then have to experience a similar environment to interact with the same genes and produce UC. Which he "according to reports" had for over 25 years without colectomy!

Then her son with his component of genetic risk would then get stage 3CRC despite multiple, multiple screenings as was indicated, and had his colon removed, underwent six months of chemotherapy.

And had recurrence where his original tumor was.....I still am uncertain of where that was. esepcially if he had a complete colectomy or if he had rectal mucosal stripping versus not.

According to literature and an excellent article from MedScape

"The cumulative probability of developing CRC is significantly higher in chronic ulcerative colitis than in the general population. Data from a comprehensive meta-analysis suggest that this probability is 2% after 10 years of disease, 8% after 20 years of disease, and 18% at 30 years after a diagnosis of chronic ulcerative colitis.[2] By comparison, the lifetime cumulative probability of developing CRC for the general population in the United States is approximately 5%.[2,3] Described in terms of relative risk, chronic ulcerative colitis increases the relative risk of CRC 5.7-fold compared with the general population.[3,4] The risk of developing CRC increases as a greater proportion of the colon is involved by inflammation.[5]"

Matt, I disagree. The more simple explanation is hereditary CRC. Autosomal dominant transmission. In that case I think patholgic testing for MSI and IHC will hurt absolutely no one. And in fact, if not performed on his original path it would have been a very, very huge miss. Genetic testing would not necessarily be indicated, but testing for MSI and IHC would be.