PubMed Halloween

In a neat turn of events I veer from Personalized Medicine and instead make note of a few Halloween Genes

The insect Halloween genes encode the terminal cytochrome
P450 (P450) hydroxylases mediating the biosynthesis of
ecdysteroids. Mutations disrupting these specific P450
steroid hydroxylases in Drosophila result in morphogenetic
abnormalities such as failure of head involution and cuticle
formation, leading to embryonic death.

How's that for Spooky...oh wait, that's a gene too. The problem here is that the scientists who named these little buggers never thought about how a person would feel if we had to say "I am sorry, your child has a mutation in the Halloween Genes" Say wha????

There are orthologues of these genes in humans. I ask all researchers to think twice. Because, frankly I am sick of saying Sonic Hedgehog to families.........

Hooray for Francis!!!!

I am so glad that the United States has decided to award Francis Collins with the Presidential Medal of Freedom. It is about time we pick up the pieces from Watson :(

On another note, has anyone noticed how expensive it is to subscribe to all these wonderful journals? I read voraciously and am thankful for my institutional subscriptions. But what if you had to pay for your information? An example is the excellent Journal Pharmacogenomics. Bundled with Personalized Medicine(Its sister journal) you end up paying 1595 USD. This is the same for many journals out there. I only pick on these journals because I deem them mandatory subscriptions for the future of quality medical care.

I would like to congratulate Dr Robison over at Omics Omics who has made it to the one year landmark with his blog. If you do not know who he is, you should. His blog is a daily read of mine and I love to listen to him discuss current topics. One of my favorite posts illustrates the power of personal genomics. Congrats Keith, Here's to another wonderful year....or ten :)

There is a neat site which I have discovered, despite not being from Chicago. The site is from the Chicago Public Radio and is called "The DNA Files" Recently they have been featuring me on their site as a "File" I would like to thank CPR (cute acronym). Everyone should take the time to look at this site. It has some very useful links, I happen to like the link to Dr Kittles work on the genetics of prostate cancer. Something near and dear to my heart...

Lastly, I would like to invite you all to review/comment/copy on Helix Health of Connecticut's new shiny website at www.helixhealthofconnecticut.org/index.htm

Thanks to Technology Review from MIT yesterday. I was featured on the blog as part of their news scan. I will say that I am not so skeptical of pharmacogenomics tests as the lead indicates. In fact I advocate and use some tests already. But we must use them in a non-panacea way. Directed testing is the future of personalized medicine...otherwise we are just continuing shotgun, one size medicine.

I still maintain that the Connectivity Map in Broad will usher in a revolution of genetic studies. This has also been shown by a physician in Michigan. He took incurable cancers and used gene-chip analysis.

For each patient, he first identified certain genes associated with a favorable response to anti-cancer drugs, and then determined an individualized treatment plan according to these findings.

What was the outcome?

4 of 6 patients in this limited study did better than the statistical average...From the post at TFOT

Lester and Webb's experiment is unusual because oncologists don't tend to be enthusiastic about basing their treatment decisions on gene profiling, especially when it might involve pairing drugs together in a novel combination or using varied doses, Dr. Lester said. He added that to truly help patients the most, all potentially effective drugs and combinations must be matched up against the unique genetic profile of a patient's tumor. According to Dr. Lester, this kind of polypharmacy will become more common in cancer treatment and at the moment, the best way to deal with issues of effectiveness and toxicity of drug doses is to build a database of gene expression data and match it with patient treatment results.

This is an important concept slowly demonstrating some proof. We do need larger studies and even greater tumor/tissue banks, but this is heartening. What I want to point out is that the Van Andel Institute is becoming a hot-bed for personalized medicine. This is a trend that several academic centers are following. Some notable ones include T-Gen/ASU, VAI, MSSM(sort of), Cleveland Clinic, Duke, I could go on and on...... So the question remains....Will you have to go to an academic center for personalized medicine? Even more pressing....should you?

What happens if everyone goes to the academic center? Long waits.....

How will we translate these trials? Corporate Genomics?? Thanks to Venutre Beat we see that it

look's like the investor is catching on to this plan.

Navigenics’ market is intended to be people who are healthy and affluent. Customers will be charged between $2,000 and $3,000 to have nearly a million genetic markers tested on a gene chip manufactured by Affymetrix. But Navigenics’ site won’t release all of the data collected by the chip, only the designated panel of gene tests. The company plans to offer information and telephone support from genetic counselors, and a subscription to its service will last a year. “Your DNA will be on file, and we’ll test it against new findings,” says Amy DuRoss, Navigenics’ head of policy and business affairs.

Not a bad idea to the trained eye. To the untrained and non-genomic saavy it appears as if the will hold your data like a pack of meanies....

Helix Health of Connecticut type practices? There are not enough of us to go around and staff everywhere!

The Internet?? Tele-Genetics?? Who'll pay that bill other than the taxpayers? Skype would be smart to enter this market.

The Sherpa Says: I am scared that the reluctance of Oncologists is not endemic it is epidemic of MOST physicians. Why? Is it lack of insurance reimbursement? Is it lack of education? Is it a healthy dose of skepticism? I wish I had all the answers....Obviously no one does. But wouldn't it be neat to ask MDs why? I am still awaiting that survey......

Pharmacogenomics Rising

Just recently released, LabCorp will study the role of polymoprhisms in cytochrome p450 2D6 and women's response to breast cancer. Which is good news for physicians like myself who would gladly use this test if their were some good data. Unfortunately, some think it is ready right now for prime-time....

Which leads me to the next topic. In the November edition of the American Journal of Human Genetics there is a systematic analysis of something called Variants of Uncertain Significance. You see, the problem that DTC testing companies don't want to tell you is that sometimes an answer only confuses things. More importantly, these things called VUSs require significant follow up. You have to double check databases and see if the genetic changes found in yourself are also found in a significant amount of those tested. And if those tested have manifested disease. In BRCA it is breast or ovarian cancer. But what happens when you pay for testing and come up with a VUS? Who translates the data? A form? A phone call?

So what is the outcome of this study? It seems that VUS are more likely to have problems if they were located in splicing sites, in the protein coding regions, or in the highly conserved areas of the gene....Makes some sense. But, you will not know the answer until you have enough patients...Which means continuing follow up....Not exactly the most scalable solution.

Lastly, Dr Bettinger comments on the ancestry article I commented on earlier.

The Sherpa Says: Would we take the tests if we knew that it may not give us an answer.......or if it gave us an answer we weren't ready to find out. What if we weren't prepared to handle what we found out? That's the role of the genetic counselor. They are there to protect us from ourselves......Or help us find what we are looking for...

Take an Antibiotic, Lose your hearing

Before I jump into the headlines I want to make mention of a few things. First, you know that there is something to these warnings I give about DTC testing when "in the Oct. 19 issue of Science, Bolnick and 13 researchers from universities across the nation call upon the scientific community to better educate the public about the limitations of the tests, and urge consumers to approach the tests with caution."

But here's the kicker. This Article.....It has nothing to do with disease testing. The buyer beware editorial is entitled "The Science and Business of Genetic Ancestry Testing"

Did you know that close to half a million people have taken ancestry testing. With 23 and Me lauching soon, I am certain that number will double in a year.

The problems with these tests are the same that come about with disease testing. Including false positives and negatives as well as limited database information to compare your alleles to.
Sounds like the VUS problem all over again.

So why lead with the pharmacogenomic title and only mention it now? Because I am not certain this test is ready for prime time. Although, there are thousands of babies getting aminoglycosides for a condition called rule out sepsis. This occurs when your baby develops a fever during the first 2 months of life. What can happen when the baby gets gentamicin? Well, in children with this change it can cause deafness. The authors in this article "Ototoxicity caused by aminoglycosides" The authors argue the merits of pharmacogenomic testing.

The most common predisposing mutation is now known as m.1555A>G, a mitochondrial DNA mutation has been well studied in China. Researchers attribute at least 33-59% of aminoglycoside ototoxicity to this change, according to studies from China.

That being said mitochondrial DNA is not always inherited to a disease causing level. In addition the authors point out the other problems"Genetic testing needs to be turned around rapidly, and consideration should be given to using an alternative antibiotic until the result of genetic testing is known."

The Sherpa Says: Well, no surprise. If there are charlatans in the medical genetic testing world where we are regulated, then imagine how ripe the field of ancestral testing is (Especially, given the lack of regulation). Let the buyer beware.....and hold the gentamicin please. Oh, and I am sick of watching the Myriad ad during Regis and Kelly!

Shame on the Sherpa

I would like to take the time to apologize for being so absent. I have been pretty busy lately, although it is no excuse for not keeping you up to date with recent news (I don't consider Watson's racist rants news. Francis would never have said such things!). Frankly, I don't think there has been any exciting personalized medicine news/articles this last week.

However, there are some interesting new blogs and sites. I find one called Mydaughter'sDNA fascinating. I couldn't imagine having a daughter with a previously undefined syndrome AND to be a geneticist. For all who are interested in how genomics can and will play a role in the undiagnosable (Is that a word?) take a good look. Thanks to Bertalan Mesko, who pointed this out to me.

The Sherpa Says: This week is the calm before the storm. I hope all of you don't mind my lack of blogging mindless dribble. I am certain next week will bring huge news!

Medicine2.0

I am sitting here listening to "Genetic Screening. What the PMD needs to Know" It is a presentation given by Monica Giovanni. Monica is a genetic counselor who works at Harvard. She is helping Dr Mike Murray build an "Adult Genetics" clinic. They have recently applied for governmental funding to set up a pharmacogenetics clinic.

I am prepping for my talk that I will be presenting at noon. The conference is called The Genetic Basis of Adult Disease. It is a CME course at Harvard and I am excited to see that we have about 140 physicians sitting in this ballroom. There are physicians from as far away as China and as near as Boston. I hope that they will take away one message......It is time to learn genetics.

What is my talk on? Adult Cystic Fibrosis. I know, you may be saying "Why not personalized medicine?" Well if you think about it. Adult CF is personalized genetics, so we are getting there. I like to bring physicians minds around by stretching them. A 74 year old woman with Cystic Fibrosis definitely stretches the mind. Oliver Wendel Holmes once said "Man's mind, once stretched by a new idea, never regains its original dimensions. " I hope to do that today.

What else is going on in the blogosphere as I "real-time blog"?

Walter has put up the Medicine 2.0 conference at Highlight Health. I must say that we ARE building the new EMR, it is not built yet....It is a work in progress.

The Sherpa Says: This weekend conference has started to prepare physicians for direct to consumer genetic testing. The president of the ACMG illustrated why the college feels that it is dangerous. Physicians here have started to view DTC genetic testing in the same light as "Coral Calcium"

Wylie Coyote? No. Wylie Burke!

In the Journal of the American Medical Association this week an article by Dr Wylie Burke has surfaced. If you don't know who Dr Burke is, then you are in the dark when it comes to true "realism" about the genome and personalized medicine.

Dr. Wylie Burke is Professor and Chair of the Department of Medical History and Ethics at the University of Washington. She is also Principal Investigator of the University of Washington Center for Genomics and Healthcare Equality, an NIH-funded Center of Excellence in Ethical, Legal, and Social Implications (ELSI) Research. Her research addresses the social, ethical and policy implications of genetic information.

From the article:

"ENTHUSIASTIC PREDICTIONS ABOUT PERSONALIZED MEDICINE have surrounded the sequencing of the human genome. As commonly used, the term predicts a leap forward in disease prevention and drug treatment, based on knowledge of individual genetic susceptibilities."

This is true. The media as well as the corporate world have "promised" some outlandish things in this space.

"Nevertheless, claims of a new medical paradigm based on genomics merit careful scrutiny. The exhortation to prepare for a “genomics revolution” often assumes that genetic risk is different in kind from other health risks."

Well, Dr Burke.....I would say that genetic risk can at times be worse than other health risks, but not at all times. This requires a nuanced knowledge base and often can not be finessed by the public or even some physicians.

"Each new genetic test will need to be evaluated and assessed to demonstrate that the overall health benefits exceed the harms before it is implemented in practice. The fundamental
principle is that genetic risk information will be useful only if it guides more effective, or more cost effective, use of medical interventions than can be achieved without the risk information."

This is precisely in line with what we tell physicians. There is no need to go off testing everyone, without good data. There are some scientists who say that data is appropriate, but unless this is peer reviewed or applicable clinically, the claim is hooey.

Here's the part I love

Personalized medicine has always been a component of good medical practice. Genetic tests may provide new tools, but they do not change the fundamental goal of clinicians
to adapt available medical tests and technologies to the individual circumstance of their patients. As genetic tests become widely available, personalized medicine will include
assisting patients to make wise use of genetic risk assessment, taking into account the cautions discussed in this article. When genetic testing is used, the personalized nature
of the care will extend well beyond the patient’s base pair sequences.

The good Dr Burke is pointing to careful clinical care and continuity of care being key to personalized medicine. I agree that not all personalized medicine is genetic. That is why no report printed on a sheet of paper will achieve the goal of personalized medicine.

The Sherpa Says: When you read this article please keep in mind that Dr Burke is a geneticist!

Interesting Readers

Over the last week I have been working on a little personal genome search project. I was contacted by one of my readers to help her find someone to "donate" her genome to. Initially I was surprised to receive such a request. Especially because I have railed against using the genome for a crystal ball.

But she was vehement that she wanted to donate her genome. Now I Have to tell you that I was then convinced of her altruism. She didn't know where to turn so we began with the usual suspects Dr Church, Dr Collins, Dr Rothberg, Hodosh. But when we were turned away a window opened.

I turns out Dr Venter's Institute is looking to turn out 10k genomes in 10 years. The perfect project.....provided these subjects have appropriate care providers to help out......

Since Helix Health of Connecticut is taking patients now, it seems only natural that we take her on as a patient.

I wouldn't have it any other way.

On another interesting note Dr Robison at OmicsOmics posts on yet another whole genome player who is entering the Archon X Prize.

Base4 (Real Cute) Innovations is pretty young and Keith covers it nicely.

Formed in 2007 with support from the University of Warwick and Warwick Ventures, base4 innovation is a group of highly talented and innovative biologists and physicists from the University of Warwick and Oxford and Cambridge Universities specialising in molecular biology, single photon detection, and nanotechnology.We are developing a new high-speed, low-cost method of DNA sequencing which combines well-known techniques such as photon detection and fluorescent labelling with nanostructures and cutting-edge methods of nanofabrication.

X Prize team leader and base4innovation founder Cameron Alexander Frayling is a researcher at the University of Warwick and the inventor of the innovative method behind this sequencing technology.

The Sherpa Says: This wonderful woman wanted to donate her genome and was turned away. I wonder who would have bit if she was willing to pay. What a shame!

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.

Gene Genie #17 and 10,000 visitors

What a crazy 5 months. It has seen the growth of the DNANetwork from 3 to nearly 30. We have seen the release of Jim Watson AND Craig Ventner's genomes. Mike Leavitt has put a manifesto for personalized medicine into the hands of practitioners, scientists, and venture capitalists everywhere. Including the funding behind 23 and Me, Navigenics, and a yet to be named third genome sequencing company. Speaking of the government, they have pledged silly amounts of money to epigenetics, creating a Genes, Environment, and Health Initiative. Sequenom has jumped in the game by licensing next-gen technology including nanopores. Oh and George Church has made his personal genome project the world's project. I am sure I a missing a ton, but I am sure you all will point that out :)

I love the gene genie, thanks to Rick Vidal we have a lovely logo too.

Before I begin, I want to thank all of you who contributed and apologize to all whom I missed. Things have gotten pretty crazy for the Sherpa and I have to thank all of my readers, including my new friends at Genome Technology Online and the 10,000 people who have viewed my blog.

The FDA put a subtle ultimatum on primary care doctors. Learn the genetics of coumadin metabolism or learn how to testify in court. Another interesting ultimatum in genetics was studied and Future Pundit captures it. Swedish Twins play the ultimatum game more similarly than non-genetic related twins.

So why do the physicians need to learn genetics PDQ? Coumadin has some pretty serious adverse effects including making you bleed into your intestines, or even worse, the closed space known as your head. It seems that the Walter over at HighlightHealth feels this an important topic too, as he covers the International Serious Adverse Events Consortium. The FDA and pharma companies will no begin to track ADEs event better and will attempt to identify even more genetic causes. Even I point out that ADEs can have devastating causes, especially when the drug intended to prevent suicide causes it.

Before I ramble on about the wonders of pharmacogenomics and personalized medicine any further, there is some significant basic science going on. Exciting science, I would dare say.

Evolgen is publishing some original research on a blog. That is what I call hot off the press.

In a revisit of what is old is new, we some some more research on telomeres and longevity at Ouroboros. Sandwalk covers the Signal Recognition Particle and some new research, and expounds on this signal hypothesis' clinical relevance.

Over at Gene Expression we learn that skin color differences are our least complex. "Based on the average pigmentation difference between European-Americans and African-Americans of about 30 melanin units, our results suggest that SLC24A5 explains between 25 and 38% of the European-African difference in skin melanin index"

To my great delight I have discovered that Scriver's has a blog and now I know we may have a cure for hypohidrotic ectodermal dysplasia in dogs. I will follow this blog more closely and it is now proudly in my RSS feedreader.

As I warn my fellow internists about the stampede of attorneys waiting to sue them for what old-school physicians may call idiosyncratic reactions, we are reminded that perhaps a little legal oversight is a good thing.

Maybe the UK could use a little more oversight as it approves pre-implantation genetic diagnosis for early onset alzheimer's disease. Hsien at Eye On DNA points out something that may have been taken care of by face to face genetic counseling. "Although I’m not questioning this couple’s very personal choice, I do wonder why they are going through PGD without knowing the potential father’s genetic status. If he tests negative, he can rest assured that his children most likely won’t develop early-onset Alzheimer’s and they would not have to go through PGD. However, if he tested positive, he’d be in the same situation of considering PGD. I understand the psychological implications of genetic testing, but what is the rationale behind this choice?" Of note CGCs don't do face to face counseling in the NHS. I recently learned this from a soon-to-be Helix Health of Connecticut CGC

These sets of issues were anticipated at the outset of the Human Genome Project but would they have anticipated the support of Barak Obama, Mike Leavitt and a little sleeper company known as Microsoft?

Well few would have been able to guess what is now transpiring. The report from HHS points out several things that need to be accomplished. All which I am proud to say have been posted on by our humble little network. The goals

Goal 1: Link Clinical and Genomic Information to Support Personalized Health Care

Goal 2: Protect individuals from discrimination based or unauthorized use of genetic information

Goal 3: Ensure the accuracy and clinical validity of genetic tests performed for medical application purposes

Goal 4: Develop common policies for access to genomic databases for federally sponsored programs

Goal 1 aims to be accomplished by Health IT. Well, they have a long way to go. Certain EMRs had no ability to distinguish maternal from paternal lineage. Hopefully Microsoft's vault will be better...BBGM doubts it and so does Constructive Health Health IT must come a long way before we can really start to appreciate its help in creating personalized medicine. How ever wil the hold our genome in their databases. This is priceless data unless you paid 100 USD while you wait. Thanks to Blaine at the genetic genealogist for this. But wait, it gets better. Illumina's CEO carries his genome on his iPhone. He either must be extremely rich and not worried about life or health insurance or he is just stupid. Thanks to Clinical Cases for this. It reminds me of when we have nutrigenomic data floating around in spiral bound report books. This stuff is privite health info PEOPLE!!!! Get a grip!

Which leads me to goal 2. How is GINA doing?

Ideally we would like to have tools such as the Connectivity Map churing in out data, but the demand on IT is probably too much. But we can at least do some neat things with genetic profiling as demonstrated at the Biotech Weblog.

Goal 3 has significant amounts of infrastructure to help with this.

And Goal 4 can be pursued through international collaboration. I look forward to the day when Berci Mesko and I can do just that. He makes comment on these things on his award winning blog.

But, alas I am brought back to reality by this post at Epidemix. Applicabilty is in the eyes of those who can behold it. Why would someone who never saw an HDL of less than 10 think of a disease that they were never taught? I guess to the non-genetically trained, personalized medicine is no big deal.

What a crazy state of affairs we have. I look forward the next 5 months and the next 10,000 new readers of the Sherpa.

Thanks for letting me host Gene Genie.

Stay tuned for the next issue of Gene Genie at Eye on DNA

Yale to study the Age Old Question

Yale will join the largest envirogenomic study to date. And when all is said and done we will have an answer to the age-old question is it nature? or is it Nurture? Or is it both? What I think is so amazing about this study is it is the equivalent of the Framingham Heart Study which has cohorted people for decades.





This study will last for 21 years. From the YSM site





The National Children's Study is poised to identify the early antecedents of a broad array of diseases that affect both children and adults," said Elias Zerhouni, M.D., director of the National Institutes of Health (NIH). "Such insights will lead to the means to successfully treat and even prevent conditions that to date have defied our best efforts."

The Sherpa Says: This precisely the right time to study this. If you think whole genome sequencing will mean anything without the data from this type of study....think again. No matter how much paper a "company" reports to you. We need data on prevention and envirogenome interaction, end of story.

Suicidal on Citalopram

The picture on the right is that of James Torlakson his daughter Elizabeth committed suicide while on Celexa.

I have been tracking this pharmacogenetic issuefor quite sometime now. Ironically, somepeople were at higher risk for suicide while on antidepressants. This had been known for some time with the drugs called SSRIs (selective serotonin reuptake inhibitors) These drugs act on a chemical in the brain which is thought when your levels are low can cause depression even suicide.

The mechanism is unclear as to how this happens. Until now we have not been able to accurately predict who may be at risk. That may soon change

Recently in the journal American Journal of Psychiatry a genetic analysis was performed on the largest study of antidepressant therapy. This study is called the STAR-D trial. There were prior genetic analyses done, but this appears the most promising.

In this analysis it appears that persons taking citalopram(Celexa) that have a change in their GRIK2 gene, called rs2518224 have 8 fold(800%) increased risk of treatment emergent suicidal risk. These are the kinds of Odds Ratios that make me perk up and say hello.

There is a pharmacogenetic test already in existence for this phenomenon. The test called Mark-C is being marketed by a company called NeuroMark and is an example of what more we shall see from labs in this space. I haven't got the specifics of this genetic test, but I have asked for more information on this. I will keep you in the loop.

The Sherpa Says: This is a very important study. However, I always caution that replication is the key to true genetic findings. But this looks pretty promising. I feel horrible for that family. Imagine how this could be prevented. However, similar data was posted on GRIK4 (not quite as good data thought)

18 Hours to Vote!!!!

Lots of things have transpired since Sunday. I would like to say first, sorry for no posts since Monday. I was preparing for my presentation at the Connecticut conference for the American College of Physicians. Second, I need more submissions for the Genie this weekend. I will be hosting my second and am looking forward to reviewing some great posts. Third, Navigenics is ready to unleash its technology on some unsuspecting consumers in '08. I know at Helix Health of Connecticut we are ready for the wave of "What does this mean?" "What should I do health wise?" etc.etc. etc.

In fact,

We just received a call from a wonderful consumer of the so-called SNP market for nutritional supplements. The big problem here is that there are SOME SNPs which actually predict risk for disease. But what do they get for a report? Eat more broccoli...Thanks.. I am scared that they don't understand about these "genes" really being a part of your medical record. Because some are as strong as a cholesterol panel in their ability to predict risk. The even bigger problem, most are not. And what happens when Navigenics gets out over the skis and says that they are? Who will be left to pick up the mess???? The fewer than 1000 geneticists? The PMDs who don't even have the training to comment on this? This is one of the major reasons why we are reaching out to educate PMDs.

I have a concern with Whole Genome Sequencing.....it really is just a snapshot in time. I emphasize the role of continuing evaluation of expression and epigenetic effects. Luckily, USC just received a bundle of dough to research and evaluate epigenetics. This is a great reason to have a continuity of care with those who have seen and attempted to interpret your genetic data. We can't keep bouncing this reductionist idea of "If we just have your genome, then we can help you live forever and cure all disease" at the market. This is what Francis Collins would call "Overselling the technology" Please answer my poll question "How much would you pay for the oversold genome?" Oops, I mean "The cutting edge achievement know as the Human genome. You should get yours done too."

I was warned by a friend of mine. He said "Shooting from the hip and having no planning of your posts is ONE WAY to blog. Another would be to plan and deliver a message." I say, why not do both. There is more than enough foolishness going on to point out. Let me know what you think.

While giving the talk today I was asked about how we can get physicians up to speed in genomics. I stated "We cannot, we have missed the boat. We were warned in 1993 and again in 2000. Medical schools never picked up the slack. Too few clinical geneticists in the basic sciences. Less than 40 Medical schools have defined courses in genetics. Up until the last few years it wasn't even a prerequisite for medical school. See the Banbury Summit. How can we teach those who never learned the language? Only one way, complete and total immersion. Much like how an adult learns a language. I have used vignettes that have clinical applicability. Unfortunately, this takes at a minimum 2 years to see any effect. If we were to do this today we might be able to make some inroads"

But physicians will not be ready for Navigenics. Boy, it sounds like this is an argument for "Direct to Consumer and Navigenics report based medicine" Well it is not why? What physician delivers care without a physical exam? One who is looking to get sued, that's who. Good luck to all the report makers. I hope you have an army of attorneys because malpractice coverage will not be enough.

The Sherpa Says: Thank you once again to Genome Technology Online I am very happy that they enjoy my musings. I hope my CGC friends did not get the wrong ideas. I am not bashing them, I am bashing the system. A system which I hope you will join me and fix.

What the F*&^

After reading Hsien's recent post, I am convinced how very much the UK needs a Sherpa. Listen to what is going on in Great Britain from Eye On DNA.

"The UK Human Fertilisation and Embryology Authority has approved the use of preimplantation genetic diagnosis (PGD) to select embryos free of the gene for early-onset Alzheimer’s disease (AD). The couple who applied has a family history of the disease on the man’s side. His mother, grandmother, and two uncles all died from early-onset Alzheimer’s."

Human Genetics Alert has been fighting the good Sherpa fight for years. The problem....the UK is still approving these techniques. I hate to tell all of you, but this is what is coming. Why scan a genome? Why do lightspeed sequencing when you have time to wait? Why? The answer is simple. To rapidly screen blastocysts to rule in or rule out suitability for implantation. I have spoken about Reproductive, Endocrine and Infertility Specialists penchant for not caring about epigenetic implications

Future Pundit talks about the role of Preimplantation Genetic Diagnosis and its ever expanding uses. The specter of looks and intelligence for PGD rears its ugly head. Do I think this is a slippery slope, you bet. Especially when at the REI conference this April there were comments such as "We are the new geneticists" and "We determine mankind's fate" were heard by my Specialist friend. Yikes here comes Aldous........

Let's face it they have yet to standardize the medium in which embryos grow. Has anyone done a solid analysis of the alteration methylation patterns that emerge while growing embryos in different media? Wouldn't it be crazy if these PGD children had some increased risk for cancer? It could happen. This is why you can't perform PGD for mildly increased risk. Why do we call a woman greater than 35 Advanced Maternal Age(AMA)? Simple, because that was the age at which the risk of miscarriage from Amnio equalled the risk of having a child with chromosomal anomaly. Now that the risk is decreased to 1 in 400 will this change AMA? So here's the question now.

Is the risk of having an epigenetic change in your genome predisposing you for cancer etc EQUAL to the risk of disease from polymoprhism in the embryo?

The Sherpa Says: Risk = Benefit is what physicians should always think about. Just because we don't know the risk DOES NOT MEAN THERE IS NO RISK!