Saturday, June 30, 2007

WBUR posts on coumadin and Personalized Medicine!

Despite the heavy Boston accent,

On WBUR Carol's worries regarding Coumadin and Personalized Medicine hit home to millions of patients everywhere. This is an excellent example of the press' coverage of my specialty. Dr Sam Goldhaber a physician at Mass General talks about the promise of pharmacogenomic testing in blood thinning and avoidance of its horrible side effects.

Lastly they interview the Pope of Personalized Medicine

Francis says "Is this the scenario we want personalized medicine to enter?"
"The public thinks that this is snake oil (i.e. Direct to consumer testing and nutrigenomics)"

In addition Dr Collins talks again about the 2 Betty's and the potential to miss diagnose and have horrific outcomes.

The Sherpa Says: "Save Betty!!!" We must take the time to educate everyone about the promise and pitfalls of personalized medicine. In My Humble Opinion, the only thing to move physcians will be the slew of lawsuits that happen after we publicize our great outcomes at Helix Health of Connecticut.

Thursday, June 28, 2007

This Week in NEJM

Table 2. Reveals risk of SSRI use in relation to birth defects.

This week in The New England Journal of Medicine 2 articles comment on a once thought problem during pregnancy. Women taking anti-depressants called Selective Serotonin Reuptake Inhibitors (SSRIs) were warned about these drugs which were considered a danger to development of the child. From one study:

Conclusions: Our findings do not show that there are significantly increased risks of craniosynostosis, omphalocele, or heart defects associated with SSRI use overall. They suggest that individual SSRIs may confer increased risks for some specific defects, but it should be recognized that the specific defects implicated are rare and the absolute risks are small......Our analysis did not confirm previously reported associations between overall use of SSRIs and craniosynostosis, omphalocele, or heart defects as a group

The problem is that drugs are not routinely tested on pregnant women. This results in an unknown effect on the fetus/child prior to giving the medicine. The only answers we have are on women who had taken a drug prior to knowing they were pregnant. This leads to very few drugs being available for use in pregnancy.

In addition to the birth defect risk there is a problem with Serotonin Withdrawal Syndrome in the child. While I was a resident in pediatrics at my prior institution I saw 2 patients in 1 month with this horrible problem. It was a tough thing to see those little babies writhing from the withdrawal. They eventually adapted to the lack of serotonin, but I wonder how well the mother would have done with the pregnancy if she was depressed.

The Sherpa Says: Is this personalized medicine? Not Really. But it does have to do with genetics and development. Besides the risk for birth defects, there is another risk for the child. Too bad it is only glossed over in these articles :(

Tuesday, June 26, 2007

The Confusing Thing About Association Studies.

Today is a moderately slow day for genetics in medicine (I can't believe I just said that). But if you want, you can sell your genome to some stranger for 5 grand USD (I can only imagine the identity theft issues) you do it at your own risk. Listen, if you are hard up for cash please do not sell your DNA sample!! Who knows what they will use it for..........Perhaps to frame you for a crime.

But what I want to really talk about is how confusing association studies can be. So lets examine some of these.

  1. Long Term Aspirin use prevents cancer incidence in colon 32%, prostate 19%, and breast cancer 17%* (statistically non-significant). There is some molecular evidence of this in colon cancer. But not the others....... The catch is that you have to use aspirin adult dose for >5 years. Why? Like most association studies.....No one knows. What good is that?

  2. Hormone replacement therapy increases Ovarian cancer incidence This study called the Million Women Study is a large cohort of British women. 948,576 postmenopausal women were assessed for ovarian cancer incidence. Users were 20% more likely to develop Ovarian Cancer. 1 in 5, that seems small, but in a million women (well......just 52k shy) that's alot of cancer!!! Especially such a nasty killer. But here's the kicker....

  3. Oral Contraceptive hormones Reduce Colorectal Cancer risk! Wait a second.....Aren't these female hormones too? This study shows an almost 40% reduced incidence of colon cancer in these women from the Women's Health Study. Perhaps this has to do with dosage? But Who Knows....It's an association study!!!

  4. Smoking Cuts Risk of Parkinson's Disease So that is what the media says about this study. Ok so now you have got me flipping out. No mechanism, No pathogenesis, No explanation.... Smoking kills, but at least it reduces your likelihood of ALSO having Parkinson's. Almost a 40% reduction in the likelihood of having Parkinson's. How? Who Cares....It's an association study! This kills me. The people could have predisposition genes for nicotine addiction/taste/etc which also have some salutatory effects. I do not think that smoking is what saves these patients brain cells!!!! But that's not what the press will tell you.

The Sherpa Says: What is sold as a good piece of science is quite often a piece of something else! Just because it was toiled over and hard work to develop it was done does not make it true, correct or even appropriate. I am here to say.....If it sounds fishy it probably smells fishy too. Throw out association studies until you have a reason for the association!!!

Monday, June 25, 2007

2 months 3000 visitors!!!!!!

Thank you to everyone who picked up my slack on Sunday. I was unable to post the Medicine 2.0 Carnival because of an illness in the family :(

I would like to tell you how excited I am that I have reached 3000 sets of eyes. I am so invigorated by this whole process of blogging. I love educating the public and physicians and this blog is a labor of love. so thank you to all the readers out there.

Lastly I would like to draw attention to an amazing film director and radio talk show host Kathleen Slattery-Moschkau . She has just produced a new documentary to the medical community called PERx…it is available for viewing via the site The film features internationally renowned experts from Harvard and other orgs. In a short time, continuing education credits will also be available to viewers and the film is also available to the general public. All for free (in order to watch the film, click on “educational modules”)

It is an amazing documentary. She has done others including Side Effects the movie with Grey's Anatomy start Katherine Heigl

Please take the time to watch this documentary as well as Side effects. You will be amazed at what you see.

Take Care
-The Sherpa

Friday, June 22, 2007

Harvard Honoring the Sherpa!

Today I was asked to be on the faculty of Harvard's famous Continuing Medical Education conference in the Genetic Basis of Adult Disease. I am extremely honored to be a part of this distinguished faculty. This year's conference will be held October 12-14th. The last conference topics and website are still up and I am certain the new one will be shortly. I highly recommend it for all physicians looking to become Sherpas or at least to stay up with the breakneck pace of genetic discovery in medicine. Several topics include:

  • Genetic Causes of Heart Failure
  • Genetics of Lipid Disorders
  • Genetics of Cardiovascular Disease
  • Genetics of Common Psychiatric Diagnoses
  • Genetics, Lung Cancer and Treatment Responses
  • Genetics of Gastro-Intestinal Diseases
  • Barriers to the collection and use of the Family Health History in Primary Care

So who should attend this great conference?

Internal Medicine Docs
Family Physicians
Genetic Counselors
Registered Nurses
Nurse Practitioners
Physician Assistants

I was at the conference last year and am excited to be behind the podium this year. Please mark your calendars!!!!

Thursday, June 21, 2007

Forbes and Genetics Season 5

Yesterday I was at the funeral for my grandmother-in law. I felt bad for her and the horrible diseases she had to suffer through. Yet I wonder, would she have smoked cigarettes if she knew that she would have to go through such misery in her last 9 years.

Notably she had 3 primary cancers, Lung, Colon and Renal. She had kidney failure and needed hemodialysis. She suffered from emphysema. She died with gangrene of her legs that was not operable and not treated by the strongest antibiotics known to man. Was that all due to smoking? Sort of....Smoking combined with her predispositions to disease put her in the hurt locker. Unfortunately she had to suffer for almost a decade. Why would anyone chose to smoke if they knew this was their future? I pose that question to you.

Without further ado. I will delve into the 7th round with the authors from Forbes.

What is wrong with these authors? Did they get any advice regarding these genes?

Round 7 FTO for Obesity

Yes, obesity is a horrible problem. We are getting fatter and sicker by the day. Except if you have a heart attack. There is an interesting piece of literature which says you are more likely to survive an MI if you are obese. Crazy, I know. But somehow it has to do with hormone signalling rather than the higher rate of correct medications being prescribed to them.

But we are here to talk about the risk of obesity with FTO polymoprhisms. True FTO is found in patients with obesity approximately 1 in 5. But how does that or could it change your life? If you had this gene would you eat less? If you had this gene could you take a medication? None are being investigated that will be ready in the next 20 years! This gene is also an at risk gene polymorphism for diabetes. Why didn't they mention that with the deCODE gene????

The gene called Fatso has so little published on its relevance in humans that it is obscene for them to include it here!!!

Sherpa 5.....Forbes 3

Round 8 Amplichip Testing for Pharmacogenomics.

Did anyone read the New York Times article on PGx this week? Hsien Lei had some nice coverage on it. The amplichip will be a key player in the role of psychiatric medications. This article explains this. More importantly it has received significant attention in the psychiatric journals. The American Psychiatric Association has issued guidelines for these tests already. Personally, we are going to speak with several psychiatrists about the implication in treatment that will take place today. Will this change your life? If you have depression....absolutely!

Forbes 4.....Sherpa 5

Round 9 IL-23 for Inflammatory Bowel Disease

From the article-A rare spelling change in immune-system gene strongly protects against developing this bowel disease, Yale University researcher Judy H. Cho says. No branded test is available, but some labs may test for this gene variant.

Will this gene change your life? If you have IBD, too little too late. The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. Another change actually predisposes to IBD. Did they explain that in the article? Did they even mention the other predisposition genes? NO. They failed you here and led you up a blind path. Likely to your detriment. Should you have the protective test? what about the predisposition test?

Forbes Failed....

Sherpa 6......Forbes 4

The Sherpa Says: Please stop smoking. If you want to avoid chronic disease, it's better than any genetic test.

Tuesday, June 19, 2007

Neglected Diagnoses: Putting you at risk!

I have decided to let the rest of the Forbes article analysis rest for today. Instead I wish to relay to you a story which deeply troubled me.

Today I saw a patient that was referred to me for the diagnosis of Osler Weber Rendu. Also Known As Hereditary Hemorrhagic Telangiectasia (HHT). What blew me away was not that it was picked up. Although alot of physicians may miss this if they fail to look in a mouth or carefully investigate nose bleeding in a patient. Trust me, these 2 things are very, very commonplace in medicine.

But what flabbergasted me was that this patient had all over his chart "May have Osler Weber Rendu"

So you may be asking yourself...Why does this matter? The answer is forthcoming. First a little bit about HHT. There are 3 types of this disease

  • Type 1 is due to a mutation in the gene endoglin, there are significant problems including masses of maldeveloped blood vessels in the body. The worrisome ones are located in the brain and lungs. If these bleed, then you can have some really bad problems including death

  • Type 2 is due to a mutation in the gene ACVRL1 and often have involvement of the liver. Unfortunately these patients need liver transplantation.

  • Type 3 is not associated with a gene mutation........Yet

The outcome in most of these diseases if left untreated is death. Either by heart failure, liver failure, or bleed in your brain.

My point and why I am so frustrated is that you can detect these AVMs and treat them BEFORE you get the horrible outcomes!!!! How? MRI of the head, CT scan of the chest, Abdominal ultrasound, and Echocardiogram.

When I spoke with the referring physician and asked why none of these studies had been done. "The answer was I didn't know to do that, neither did my colleague. I thought these things only happened in childhood. Shouldn't it have been done there?" My response was......"well you should do it now and adults have genes too." This man has a daughter and grandaughter, he has familial implications that could have been addressed prior to the birth of his grandaughter.

The Sherpa Says: No you do not have HHT if you have a nosebleed.....But you might if you have funny things on your tongue and chronic nosebleeds. Please don't assume your doctor knows how to do the right thing. Be proactive, take charge of your healthcare. And if you need to email the Sherpa.

Monday, June 18, 2007

Forbes and Genetics Part 4

Sorry I took off Sunday. I just want to take the time to make a public service announcement. Please talk with you loved ones about your wishes if you were to have a terminal illness. Sometimes these wishes can not be conveyed and this will lead to horrible outcomes. So please, please have a living will.


Now back to the slugfest!
I have received even more emails about these postings. Luckily none from Lawyers yet ;)

Round 4 BRCA1 and BRCA2:
From the article-One in 500 women have mutations in one of these genes, which normally keep tumors from growing. That gives them a 50% to 80% lifetime risk of breast cancer and a higher risk of ovarian cancer, too. The test costs $385 for women of Jewish ancestry who know they are at risk for a particular mutation. A broader test looking for any defect costs $3,120.
Succinct, accurate, and applicable. However, they did not get into BART testing as I had posted about in my Blame Portugal segment. The also did not point out that BRCA testing can detect pancreatic and prostate cancer risk as well. This could have been much more informative and useful............Sherpa 3 Forbes 2

Round 5 OncotypeDX:
From the article-This test looks at 21 different genes that can be out of whack in a breast cancer tumor and predicts how likely cancer is to come back after surgery. That helps women decide whether or not to get chemotherapy, which can cause side effects such as nausea, hair loss and numbness. The test costs $3,500 and is covered by MediCare, UnitedHealthcare and Aetna.
I am not so sure "out of whack" is the best way to describe this testing. Perhaps, "whose expression leads to poor outcomes and recurrence" is a better way to describe it. Well, I am one to mince words myself so I can't get too picky. But the answer is...Absolutely an important test. This has been proven, validated and replicated.
No doubt this round goes.....Sherpa 3 Forbes 3!

Round 6 TCF7L2 testing.
From the article-This variant, in a region called TCF7L2, doubles the risk of adult diabetes if you have two bad copies of it--10% of people do. It is the strongest diabetes-promoting gene yet discovered. DeCode Genetics sells a test for $500 via online test provider DNA Direct.
Ok, before I go slicing into this test several caveats. 1 I absolutely abhor testing for the sake of testing. Especially when the result is not definitive. It leads to confusion, poor compliance and a false sense of security. I am disgusted by this type of testing. Especially when just one sibling with diabetes gives you greater information.

Now to the dissection of this claim. First, this polymorphism is a good and replicated polymorphism. But not everyone with diabetes has this change. The gene is about risk and there is no study available which show there are significant steps you can do to mitigate this specific gene risk. True you can diet and exercise just like you would to prevent diabetes anyways. In addition, the increased risk given by just this one polymorphism is not that significant. What is more likely to change your life is a panel such including genes identified by Dr Collins et. al. This study was published before the Forbes article and they easily could have mentioned all of these genes in one part. But they did not. Why? I think it has to do with the ties to deCODE. But that's just the conspiracy theorist in me.

I have an issue with this quote-"It is the strongest diabetes-promoting gene yet discovered."
Wow!! In what population? There are other genes in populations not northern European that have higher risk. This statement is almost false!!! Frankly I think we should take a point away from Forbes for this. But I won't.

Sherpa 4 .... Forbes 3

The Sherpa Says: I love how the media mixes true things into their agenda. It is a sneaky way to appear factual and credible. If they would have to submit these things to peer review before publishing, then we would have a different story. How come no one holds journalists to scientist standards? Especially when writing about Science!!

Saturday, June 16, 2007

Forbes and Genetic Part 3...The Genes

So after that long and drawn out search I am most interested with the genes that these guys chose and why they chose them. I am surprised this article wouldn't have been written by a scientist or maybe a clinician. They would probably be in a better position to say how these gene polymorphisms/tests will perform.

  1. Complement Factor H LOC387715; In people with bad copies of these genes, chances of macular degeneration progressing from an early, mild form to a severe one increase 10-fold to almost 50%, according to a study in the Journal of the American Medical Association. Ok so this is true. There is another gene HTRA1 that should have been included. Together these two gene polymorphisms increase your risk of AMD by 40 fold! Also there should have been some mention of the fact that there is some preventative measures you can take now with this disease including eye drops, antioxidants and diet (Fish). Also carotenoids (so eat your carrots!) Or you once you get AMD you could get injections into your eyeballs to prevent progression...Carrots are sounding a whole lot better! 1st round.......Forbes 1 Sherpa 0
  2. The next up Apolipoprotein Epsilon 4 variant. The problem...Alzheimers Disease, we have gone over this problem before here. Jim Watson PhD knew that this predisposition was iffy at best. But as I state in my previous post perhaps with analyzing GAB2 we can come up with a clearer picture. But if Dr Watson doesn't want the results....Why should you. I gotta say this pick is pretty poor...for now. Especially because they don't even mention the possibility of modifier genes or Prevention (any ideas?) Round 2......Sherpa 1 Forbes 1
  3. Number 3 isn't even a gene. It is a linkage locus. Chromosome 9p21 and the name deCODE shows up! OMG, this one has got me hopping mad. There are so many other linkages, why does this one show up? This increases your risk by 30% only if you are a Caucasian Perhaps a genetic panel should be mentioned. Well, I could name 4 polymoprhisms that show greater risk. And a family member with a heart attack at any age increases your risk 250% take that deCODE! Round 3 goes to the Sherpa, ....Sherpa 3 Forbes 1

The Sherpa Says: I think breaking these up into groups of 3 will be better for all of us. Tomorrow I will write about 4-6. Are you already getting the sense that these guys had no clue what they were talking about?

Forbes and Genetics Part Two

Given the recent emails I have received I will now present the other author to the 12 Gene Tests That Could Change Your Life Matthew Herper. It turns out I am not the only person trying to find out who Matt Herper is. But I am slightly daunted given the fact that WikiAnswers hasn't been able to answer this question.

Why investigate the authors? Because they are telling you that these tests could CHANGE YOUR LIFE! Frankly, I wonder who advised either of these guys. True, they are medical writers for several years. But there is always someone who advises a writer......

So once again I dial up spy-engine Google.....

Mr. Herper focuses on science and medicine both for the print and online editions of Forbes and is tasked with devoting about half of his time to each.

What kind of Bio is that? So he is under 30 years old. So that tells me something. He is not likely a PhD or MD although he could be either without post doc training..... Wait a second.....Under 30? I bet he has a LinkedIn profile. I know that I do.

Bingo Whoah. I got the feeling that he is hiding his credentials. Why? Even his profile is extremely spartan. Sketchy.....He moderated a biotech Industry panel and I thought his credits might be found luck

Finally 11 pages deep into the google search I find this From the Counterpoint Archives at MIT

Matt Herper '99 (
drinks occasionally but finds that reefer makes him ill.

Graduated in '99 could be 29 now....Sounds like we have our power player. Guess what MIT and Matt Herper find.....Friendster Impressive bio. Nothing here nor there indicating his opinion on Myriad or deCODE.

So now that I have identified the authors. We can take a look at the tests one by one.
First up Complement Factor H polymorphisms.......

Friday, June 15, 2007

Thank You!!!!

I just wanted to thank all of you who read this blog daily. I am so excited about personalized medicine and the promise it brings. Without your comments and opinions I would only be one voice in this sea. In addition I would like to take the time to thank you for landing me in the Health Care 100! Sponsored by the ranking is a set of the top 100 health care blogs in the blogosphere. I am proud to be part of that 100 after just 3 Months of posting. I can't wait to say 3 years of posting. I can't wait to say 30 years of posting. I lastly want to thank those who accepted me into this community so warmly. Namely, Hsien Lei, Bertalan Mesko and Ricardo Vidal. We may not agree on everything, but we definitely agree on how great the future of medicine and genetics will be. To anyone else I failed to mention I thank you as well, just leave a comment and tell me how mad you are that I forgot to include you ;)

The Sherpa Says: Here's my promise; To guide you through the progressive realization of Personalized Medicine, To keep you from adverse drug reactions, To help you Prevent disease, To help you identify risk, and to protect you from charlatans looking to make a quick buck at the price of your health. I dedicate myself to this for the sake of all of us.

Thursday, June 14, 2007

Forbes and Genetics

Way back in 2004 Forbes published an excellent article on inflammation and heart disease. That article introduced me to deCODE. In fact, I was so impressed with their model I began to read about their founder voraciously. More importantly I began to see the wonderful role the media has to play in this new revolution. They can influence the demand just as much as Myriad spending 1 million in Denver to market to consumers. Granted these publications don't have the Oprah Effect (Did I mention that Dr Oz is going to meet the Sherpa?), but they do have some teeth!

But I was also distressed when Forbes published an article that I had a tough time swallowing. In fact it brought me to tears. How can this publication blindly validate and promote these tests without any medical guidance, or suspect guidance at best. I am certain you have all read this article, but you can read it here. The wonderfully hyped name 12 Gene Tests That Could Change Your Life says it all. But before I get into the article, which is misleading and not factual enough to guide decision making, I will investigate the authors via my favorite little spy...uh I mean Search Engine Google ;)

Robert Langreth. He has written many articles some good, some bad. He has been writing about deCODE since 2003 prior to the Big Forbes cover story in 2004. He has been writing about personalized medicine since 1999 as Staff Reporter of THE WALL STREET JOURNAL. He also has written many scathing reports about drug companies, which is why I find it ironic that he endorses deCODE's diabetes test. Which does not tell you as much about your risk as if you had a first degree relative with diabetes. Mr. Langreth was a Staff Reporter at the Wall Street Journal from 1995 to 2000 and an Associate Editor at Popular Science from 1992 to 1994. It was at this time in my search when I figured it out

From a chat in 2002
mherper: What's Kari Stefannson like in person?
LANGRETH: Kari is a charming and very emotional person. He literally had to sell his radical database to an entire country. He did it by a grass-roots campaign, going and speaking to anyone who would listen. He eventually by weight of personal charm won the day over his opponents.
mherper: How can you write about DeCode Genetics when their stock is at $2?
LANGRETH: I wasn't recommending them necessarily as an investment, although I'd argue that it is not a terrible deal right now. I chose them because Kari is doing something that will very likely change the course of science and lead to fundamental discoveries. Whether it leads to a successful business is another question entirely. But since you ask, I figure that unlike many tiny biotechs, DeCode has something unique--the genetic access to an entire country. It doesn't mean they won't go out of business someday. But in the meantime, they are almost certain to have a big impact on science.

Does he have stock in DeCODE??????? It did track up on the day of publication.

We have to be careful to fully investigate our sources. Whom do you trust when giving you information about genetic testing? The company spokesman? The company that sells the tests? What about the middle man? We are entering nebulous waters where the lines of relation can still be hidden. Even from google. When you publish for a peer reviewed journal you have conflict of interest disclosures required. How come we don't have the same for a well read and respected magazine/website?

The Sherpa Says:
Mr Langreth has done some crack reporting on several topics, but to include the DeCODE TCF7L2 test as one that will change your life is a HUGE LIE!!! This test is a party trick at best, a distraction that could lead you to not getting your fasting blood sugar tested (The standard of care for early diagnosis). At best he just boosted deCODE stock. At worst he led you down the wrong trail. Be careful, some who play sherpas actually have stock in the pack the tell you to carry.

Wednesday, June 13, 2007

Personalized Medicine since 1986???

First I would like to apologize for the lack of postings on interesting topics lately. I am glad that others have picked up my slack. Notably Hsien and Bertalan's interesting posts this week. Or for an in depth post on the politics of health care and the reform movement check out VentureBeat

What I want to pay attention to today is the question I inevitably get asked when I speak to other physicians. "Is what you say feasible in a 7 minute consult world?" The answer is inevitably NO. I do not feel in my heart of hearts that we will ever be able to practice personalized medicine in a 7 minute consult world.

What's needed is a Revolution. We need a place where the patient has access to their records and their physicians 24/7. We need a place where the patient is given the skills to understand and manage their disease. My friend's 12 year old son can quite effectively manage his diabetes, how come a 45 year old venture capitalist cannot? Support is the key and learning is the motion required to open the lock. How do we make these things easier? How can we get doctors to teach their patients? What ever happened to true continuity of care? These are big questions that need answers. I don't have them all. But I am working with some great people who will find those answers.....

So the next question is "How can we have the knowledge to practice these things?" I often tell physicians to go back to college or read a book on genetics. If you don't have the time to do that, then you will fail your patients. This often meets an uproar of disbelief......I am pretty good at pissing people off. Just ask Lisa Lee at DNADirect ;)

In all honesty, we need some clinics who offer personalized medicine consultations. These specialists need to guide care in collaboration with PMDs. I am building this model in NYC! We will be seeing patients in July. Give me a call and we can arrange to start the relationship.

But there has been someone doing this since 1986!!!! Wha??? The HGP was only 3 years in and they were providing these services. Yes that is correct. Greats such as David Rimoin and Maren Scheuner helped form and develop this practice. It goes by the "trademarked" name GenRISK Adult Genetics Program. It has been in practice since 1986 offering several tests that you can see on their site. I have been critical of predisposition tests unless clinically indicated. This is an example of how a personalized medicine practice can be run.

The Sherpa Says: Genomic and Personalized Medicine need to be given in a continuity of care. Family history changes, medical history changes. A one time consultation cannot deliver that kind of service. Oh and what about pharmacogenomics?

Monday, June 11, 2007

Why Watson Didn't Want His ApoE4 Results.

Alzheimer's disease (AD) afflicts about 10% of persons over 65 and almost half of those over 85.

When Jim Watson had his genome sequenced he asked not to have his ApoE4 status revealed. Why??
Dr Watson did not want to know his genotype status because although twin studies suggest that there are several susceptibility genes which, along with the APOE 4 allele, contribute to up to 80% of LOAD (Late Onset Alzheimer's Disease) cases, the story is nowhere near being finished. Not everyone with APOE4 gets Alzheimer's. In fact, the majority do not......

But the picture for those predisposed is getting clearer.

This last week a study was released by the team at TGen (Translational Genomics) in the journal Neuron. According to the study:

"...suggests that the gene - called GAB2 - modifies an individual's risk when associated with other genes, including APOE4. The study results appear in the June 7 issue of the prestigious peer-reviewed journal, Neuron."

"The team screened the DNA from 1,400 individuals who had been clinically assessed with Alzheimer's prior death, and simultaneously examined more than 500,000 SNPs or genetic variations to characterize and confirm additional LOAD susceptibility genes. The search revealed GAB2."

The polymoprhism is known as SNP rs2373115 . It interacts with APO epsilon 4 to prevent neurofibrillary tangles. This protein is over expressed normally in APOE4 afflicted brain cells.

So what does this mean? GAB2 normally acts like your mother. Remember when you made a mess of your room? If you were lucky, your mother cleaned up the mess. You kept making more of a mess and she kept cleaning up. If your mother didn't clean up, then your room was a constant mess. Even worse, you couldn't find anything in your room that you needed. Much like the way an Alzheimers patient can't find their memories.

In the end a Non-cleaning mother and a really messy kid led to a very dirty room. Just like the combination of GAB2's SNP and APOE4 lead to an odds risk of 4.06 a 400% increased risk.

The Sherpa Says: I agree with Jim. ApoE4 testing can often be uninformative with only 25% of those with the gene polymorphisms going on to get Alzheimers. I think family history will have to lead the way. At least until we have a GAB2/ApoE-4/new gene panel that puts together the picture much more clearly.

Saturday, June 9, 2007

Not all drugs benefit all man!

While Bertalan Mesko at ScienceRoll is introducing us to the best medicine 2.0 tools, i am reviewing some results from the American Society of Clinical Oncology meeting last week.

In another example of how we need to examine patients pharmacogenomics prior to instituting therapy the SWOG (South Western Oncology Group) in the U.S. releases results of a collaborative effort with two clinical groups in Japan (Japan Multinational Trial Organization).

The researchers were interested in how these different groups metabolized certain chemotherapeutic agents Paclitaxel and Carboplatin. Now what is interesting about this study presented at the ASCO conference is the fact that they were able to isolate two gene polymorphisms responsible for these effects.

In patients with certain variations in the CYP3A4 gene, it took 2.75 times longer for their lung cancer to progress than in patients without the variations. A variation in another gene, ERCC2, appeared to interfere with how well patients responded to treatment.

The problems with this type of analysis are threefold.

  1. The study was too small a size to not need replication

  2. The study did not involve the genome of the tumors (Perhaps the DNA repair mechanisms in the Caucasian tumors were better. This would like to decreased cell death i.e. response to chemo. As with the tumors and ERCC1)

  3. The dose of chemo was not controlled (although the lower dose worked better in the Japanese)

The Sherpa Says: In order to make useful sense of Personalized Oncology we must look at genomes of both the cancer and the person. I feel that we are introducing erroneous data to confuse us. I hope The Cancer Genome Atlas will show us some better data!

Wednesday, June 6, 2007

Part 3 of the Personalized Medicine Revolution

The third post of the conference at Brown will cover a round table. This forum was moderated by Professor Charles Ogletree of Harvard Law School. The following persons were involved in the forum:

  • Healthcare Translation – Daniel J. Wattendorf, MD, MAJ, MC, USAF, Keesler Air Force Base
  • Ethics – Thomas H. Murray, PhD, President & CEO, The Hastings Center
  • Patient Advocacy – Sharon F. Terry, MA, President & CEO, Genetic Alliance
  • Privacy – Joy L. Pritts, JD, Research Associate Professor, Health Policy Institute, Georgetown University
  • Research – FrancisS. Collins, MD, PhD Director, National Human Genome Research Institute
  • Institutional Review Board – P. Pearl O’Rourke, MD, Director, Human Research Affairs, ESCRO Chair, Partners Healthcare; Associate Professor, Harvard Medical School
  • Legal – Richard A. Johnson, JD, MS, Senior Partner, Arnold & Porter LLP
  • Economics – Edward Abrahams, PhD, Executive Director, Personalized Medicine Coalition
  • Media – Jonathan D. Rockoff, Reporter (Washington Bureau), Baltimore Sun
  • Insurance – James E.Purcell, JD, President, Blue Cross Blue Shield, RI
  • Hospital – Joseph F. Amaral, MD, FACS President and CEO, Rhode Island Hospital
  • Pharmaceutical Industry – Patrice M. Milos, PhD, Executive Director, Pfizer
  • Politics – Paul T. Kim, AB, MPP, JD, Partner, Foley Haog LLP

Professor Ogletree posed the following situation. "Terry is a 25 year old woman who has just used Google's Health Kit and searched her family's history. She finds 2 maternal aunts with heart attacks in their forties. Who does that matter to?"

First he asked her PMD. "Does this matter?" The PMD representative was a physician from the Air Force. He said-"I don't have any guidelines on second degree relatives. I don't know what to do" Obviously he didn't read Maren Scheuner's articles.

Next Dr. Ogletree asks what other tools might she have used. Dr Collins answers that there is a study going on at Harvard where all employees were encouraged to input and utilize a family history tool. There will be an evaluation of pedigrees and risks.

Dr Ogltree then asks "What are the discrimination risks?" That is when the panel caught fire. Joy Pritts starts by stating that each state have different regulations, and that these regulations are filled with loopholes. She also states that Rhode Island has some of the best protections available. "Don't ever move! Because your protections don't follow you!" "I hope she doesn't work for Wal-Mart she says" Mr Kim then chimes in...."What's in the google box? What are they doing with your data? How protected is it?"

Professor Ogletree then shifts gears "This 25 year old woman receives an email from a Pfizer clinical trial coordinator offering enrollment. Should she join? What about protections?"

It is becoming evident that the existing legislation throws you to the wolves. Patrick Kennedy seated quietly in the crowd can barely contain himself and starts shouting at the crowd. He says HIPAA doesn't protect you. In fact if your provider or company utilizing your data (i.e. for research) goes bankrupt that your data is no longer protected.

Dr Milos of Pfizer then chimes in....."I don't think Pfizer is going bankrupt any time soon. She should enroll." Then Dr Collins quips "Who wants to place bets on that?" The crowd erupts into laughter.

The Sherpa Says: The moral of this roundtable was that there are online companies offering services. Who is to say that they won't go bankrupt and put your info out there. Only medical practices actually have the kind of protections a patient needs. No DTC company can be held liable for "losing/selling" your data, especially if they go bankrupt. In addition we learn that most PMDs are unaware of the significant role family history plays. The take home point is that the medical infrastructure is ill suited for this next transformation in medicine and Google is likely to give you more information about genetics in medicne.

Coumadin and Buccal Swabs!!!

Prior to posting part 3 of the Brown conference I had to put Kimball Genetics on the Radar! The have devised a test to help with the scourge of Adverse Drug Reactions and Coumadin! Coumadin/Warfarin is designed to thin the blood and prevent clots causing stroke and pulmonary embolism. The test detects specific variations in the CYP2C9 and VKORC1 genes, the presence of which result in lower dose requirements for warfarin/coumadin. To help with implementation the nice people at Washington University, St Louis. The interactive website at has been developed by Brian F. Gage, MD,MSc, colleagues and is ideal for this purpose.

With every test their is the Good, The Bad, and the Ugly.

  • The Bad? Turnaround time is a day. At the American College of Cardiology conference there was a claim of 1 hour turnaround time with an unspecified test!

  • The Ugly? Will physicians know to advise patients of the familial implications of these tests? And will the 2 million plus people on coumadin be able to understand the counseling?

  • The Good? This test is 99.9% sensitive and accounts for over 35% of coumadin metabolism variation

The Sherpa Says: I have to go tell it on the mountain....but I will be back to go over coumadin metabolism and this test in a finer detail. For now, hold tight and get some help with test interpretation if you plan to use it.

Tuesday, June 5, 2007

Dr Collins reports from the Front Lines

In the second of my 3 maybe 4 part post I will detail Dr Collins' report from the Front Lines of the Revolution!

First some notable quotes

  • "2007 is going to be a landmark year in Genomics and Medicine"

  • "We all have ticking timebombs in our genome, you could guess most of them from family history.........But not all of them"

  • "We shall have the major genetic risk factors for common diseases in 2-3 years or less"

Without further ado I will break his talk down into sections. Dr Collins', feel free to correct anything in this.

"Notes From the Front Lines"

  1. DNA sequencing is undergoing a revolution. I almost felt that he had been reading The Sherpa prior to giving this lecture. I had commented on 454 recently. On powerpoint he showed the technology behind 454 and Illumina. he did not comment on nanopore, but I think that's because it is not ready for prime time. In addition he did not comment on RainDance..............I feel he knows something big is going to happen in sequencing real soon.

  2. Common Disease gene discovery is skyrocketing. In this subset Dr Collins draws our attention to several great discoveries. He talked about GWAS (genome wide association studies). He even mentioned the numbers and power required to get a decent study. I am always amazed by how the public and physicians think this type of stuff is easy! He made mention of the macular degeneration studies which implicate 2 gene polymorphisms in over 50% of the disease!!! He spoke about Diabetes, something that he has been studying for 14 years. He did not metion DNADirect and DeCode's TCF7L2 testing via DTC........ I think this is a hot topic. Especially because Sharon Terry was at the conference. A great woman who is now advising DNADirect. She is a patient advocate in the truest sense. Without her GINA would not be around.

  3. Diagnostic capability is advancing. In this subgroup Dr Collins mentions Abacvir toxicity and pharmacogenomics testing. He also give us some insight into the pharmacogenomics process and how we can use these tests. By this time my teams' heads are spinning. I am reminded of my prior post. Coumadin was mentioned by Dr Collins too, the 1 hour test was not. Trust me, this flank is moving full speed ahead!

  4. ELSI needs to be addressed “Will we increasingly think of ourselves as hapless victims of our genotype?.......Attention to ethical, legal and social issues is more important than ever,” Dr Collins aptly points out the fact that we have some serious loopholes in our legal protection. In addition, we have to think about ALL of the uses and misuses of this information. Later on I'll tell how Representative Kennedy is super focused on this topic.

The Sherpa Says: Ok, this is too much info. Let's digest this and move on later today..... Oh and Francis is the Man!!!

Watson, Francis.....and The SHERPA!!!!!

Remember how I said that June is going to be one heck of a ride? Well, what a way to kick it off. Yesterday I attended the "Personalized Medicine Revolution" at Brown University. My team drove 3 hours from NYC to Rhode Island to attend and trust me....It was worth it. I want to recap in some coherent and readable fashion so I will break it into 3 posts throughout the day.

Post 1 The Welcoming Remarks by Dean of Brown Medical School Eli Adashi and Rep. Patrick Kennedy.

I find it interesting that the introductory remarks are given by an REI specialist. Especially after what was disclosed to me.

"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........"

In addition, the lack of REI oversight in this country was addressed by Dr Thomas Murray PhD CEO of the Hastings Center . But I will save that for a later post. Dr Adashi did make a funny though. He showed a slide of Jim Watson receiving a copy of his genome on CD from Jonathan Rothberg. Dr Adashi said "I am happy to say I just received my copy from Netflix!" to the laughter of the crowd. Lastly he closed with a comparison many of us make. "Just like the microbiology revolution...........Genome based medicine is inevitable and It's here today."

Still, the welcome was warm and the stage was set for an exciting day of "Personalized Medicine!"

The next comments came from the sponsor of the conference, US Representative Patrick Kennedy. First I would like to say I have no political attachment to either party so what follows is merely my observations as a citizen of the United States.

At first it was difficult to understand his accent. Second it was tough to listen to his ummmms and uhhhhs. Thirdly he had a tendency to say "you know". But once I got past the "nerves/Billy Madison-isms" what he had to say was pretty amazing. Representative Kennedy is a huge ally in the fight for the right drug, for the right person, at the right dose. He went on to detail how proud of Rhode Island he was, he talked about his mental health initiatives and how personalized medicine will help those with mental illness. Frankly, I was very impressed with what support and knowledge came from his mouth.

Next post............Francis Collins and "Reports from the Front Lines of the Revolution!!!"

The Sherpa Says: Viva La Revolucion!

Sunday, June 3, 2007

June comes Crashing In!

I am sorry it has been 2 days since my last post. Things have gotten crazy recently. I started with the launch of my personalized medicine practice. We are busy dotting the i's and crossing the t's. We have a truly "flat" organization and are able to grow at a moment's notice. This is great news for the patients! Several things are happening in this week and I want to share all of them with you.

  1. My wife, daughter and myself were involved in a car crash. I want to remind everyone to please wear your seat belts. If you have children please make sure they are in the appropriate car seat for their age. These simple things allowed us to walk away unharmed. Sometimes it is all about the prevention.

  2. At Brown University there is a conference being held, Frontiers of Medicine. My team from Helix Health of Connecticut will be up there listening to notable speakers, including Dr. Francis Collins. I look forward to him accepting a position on our scientific advisory board.

  3. Hsien has posted on a subject I feel very passionate about, predictive, preventative medicine. If PTC-124 works out the way everyone feels it will, then we are looking at adjusting environment to avoid disease. I think this is precisely why the co-funding at NHGRI and NIEHS is so important. Because once we find predisposition we need to find out all the environmental effects. Otherwise we just know you are at risk.
  4. Lastly, the Gene Genie is coming. I would like to thank Hsien for hosting this month's edition and Berci for motivating me to post. Have a look at Eye on DNA!

The Sherpa Says: Buckle up. June is gonna be one heck of a ride!