Saturday, December 29, 2007

Welcome to Helix Health of Connecticut

Well, I have been getting alot of questions regarding our personalized medical practice on Park Avenue in New York City. I have been reluctant to tell everyone, but I figure that I might as well let everyone in on our "secret"

My philosophy is the power of genomics should empower patients and providers.

Together as a team we can prevent some horrible diseases and avoid some horrible adverse drug reactions. How do we do this? We take the skills from a multidisciplinary team and identify risk. We feel that the most powerful genomic tool out there is family history (Sorry Hsien). This has been validated over and over again in epidemiological studies. In fact when Mike Leavitt indicate in his foreward of his Personalized Health Care report

"One part of the foundation for such a change is our rapidly growing understanding of the human genome and the processes it directs. We envision health care that could:

  1. predict our individual susceptibility to disease based on genetic and other factors;
    provide more useful and person-specific tools for preventing disease, based on that knowledge of individual susceptibility;

  2. detect the onset of disease at the earliest moments, based on newly discovered chemical markers that arise from changes at the molecular level;

  3. preempt the progression of disease, as a result of early detection;

  4. and target medicines and dosages more precisely and safely to each patient, on the basis of genetic and other personal factors in individual response to drugs. "

I thought he had read our business plan. But then I realized, anyone with an insider view would have to conclude the same thing. This IS personalized medicine. I think that the fields we will see explode are services which Helix Health of Connecticut is offering.

The problem I have always had with academic genetics is 3-fold.

  • Most geneticists are pediatricians (8 in 10) and have not been trained in adult chronic diseases or even used most medications that are intended for adults.

  • Traditional genetic care offered in the "Ivory Towers" is diagnose and adios. They have no desire to offer close follow up. In fact, in the time that I worked at an academic center we did very little to recontact those difficult clinical genetics cases. Only metabolic patients get the close follow up needed.

  • There is NO privacy at a big center. In most places you are pushed through like a means to an end.

  • The last problem I have with traditional genetics lies in how we acquire medical information.

In a clinical genetics appointment of 45 min to 1 hour you get a fam hx from the genetic counseling student which takes 20 minutes, they attempt to take a medical history (despite having no medical training), they then present to an attending or fellow (10-20min), who then comes in a confirms the information. Now with 15-20 minutes the attending has to explain complex genetics and inheritance to you, send off subtelomeric, CGH, karyotype, genetic tests, etc. And you get ONE follow up appointment and may wait 6 months for another appointment.

In a cancer genetic situation you do have more time. Perhaps if your counselor is good, you get adequate follow up and acquisition of information. You may be seeing a geneticist (Who has not trained in adult oncology) or you may be seeing an oncologist (Who never trained in genetics) If you even see a physician at all. This is not to knock my CGC friends. They have truly great talent and training, but learning what to do with your Plavix is not one of them. In fact our head counselor said "When I took a family history and it looked like there was early heart disease I said to myself 'I know something is there, but what do WE do about it?' Therefore the problem lies in the training or perhaps in the team.....

And please do not get me started with the Chop Shop known as "prenatal genetics/high risk OB clinic" Where the standard is to get as many people as possible into and out of the counselors office and the into and out of the amnio as quickly as possible. Where is the CARE in that? Is there any PRE-Conception care out there? There is at Helix Health of Connecticut of CT!

What kind of medical informatics system is employed at most academic centers? Archaic at best in most. At least where I and my partners have been. When even the highest powered EMRs cannot distinguish between maternal or paternal lineage, then you have a problem.

Lastly, where is pharmacogenomics? Where is chronic disease risk stratification? Oh I forgot, geneticists don't do this, nor is there training for this in classical genetics fellowships. All of this and more is available in my vision of what personalized medicine should be. Helix Health of Connecticut is Personalized Medicine for the 21st Century(TM)

The Sherpa Says: Helix Health of Connecticut of CT is my dream, my vision and the tip of the personalized medicine spear. I know this may seem like an advertisement, it is not. It is the road map which all personalized medicine practices should follow. When you take Prediction, Prevention and Privacy to the highest standards of care, you are bound to succeed. Interested? Email

Wednesday, December 26, 2007

Highest Breast Cancer Risk! Hispanic women.......and Men!

In the December 26th issue of the Journal of the American Medical Association an article caught my eye. It turns out that Hispanic women(and men) have the highest carrier rate for BRCA1 mutations aside from the Ashkenazi Jewish population.

The study sought to identify carrier rates among several different ethnicities. This is important because traditionally we have had little data on women of color as well a worse outcomes in African American and Hispanic women with breast cancer. There have been several hypotheses for this.

This study performed by the Northern California Cancer Center had methods of design where they sought "patients younger than 65 years with newly diagnosed breast cancer and meeting defined eligibility criteria, and their family members, were enrolled

This analysis is based on women diagnosed with invasive breast cancer between January 1, 1995, and December 31, 2003. Patients were identified through the population-based Greater San Francisco Bay Area Cancer Registry, which ascertains all incident cancers as part of the SEER (Surveillance, Epidemiology, and End Results) program and the California Cancer Registry.

We recruited patients with oversampling of patients having characteristics suggesting an inherited basis for their cancers.

In stage 1 of sampling, we administered a brief telephone interview to all patients and assessed self-identified race/ethnicity and family history of breast and ovarian cancer.

In stage 2, we invited all patients in category A and a random sample of patients in category B (2.5% of non-Hispanic whites and 33% of all other races/ethnicities) to enroll in the family registry.

Participants completed questionnaires on family history of cancer and breast cancer risk factors and provided a biospecimen sample.

This 2-stage sampling design provides unbiased estimates of mutation carrier prevalence having greater precision than those obtained from a simple random sample of the same size.

What did they find?

Among African American, Asian American, and Hispanic patients in the Northern California Breast Cancer Family Registry, the prevalence of BRCA1 mutation carriers was highest in Hispanics and lowest in Asian Americans. The higher carrier prevalence in Hispanics may reflect the presence of unrecognized Jewish ancestry in this population.

In the editorial after it states a similar quandary

What are the reasons women are not offered genetic counseling and testing as part of a comprehensive risk assessment program? Are minority patients less likely to accept genetic counseling, or are there barriers to physicians offering the test to minority women? A recent case-control study found that African American women were 78% less likely to use genetic counseling and BRCA genetic testing than white women. Data on BRCA testing from Myriad Genetics Laboratories showed that less than 10% of individuals tested were from minority populations, such as Hispanics, African Americans, Asian Americans, and Native Americans.

Given that most literature on genetic testing has focused on Ashkenazi Jewish and non-Hispanic white women, it is conceivable that clinicians are not aware of the clinical usefulness of BRCA testing among US minority populations. To compound the problem, most of the available risk assessment tools were developed using empirical data collected mainly in non-Hispanic white populations. Their applicability in other populations is uncertain. Other models were developed based on mendelian principles and the Bayes theorem. Of these, the BRCAPRO model has been widely used in the genetic counseling setting, and its performance has been evaluated mostly in white populations. However, as an essential parameter of the BRCAPRO model, the prevalence of mutation carriers is available only for the Ashkenazi Jewish and non-Hispanic white populations.

The Sherpa Says:

If you are using the Gail are putting yourself at risk for missing cases. In addition, not all BRCA carriers are Ashkenazi. Maybe insurers need to wise up and start covering testing for other ethnicities as easily as they do for the Ashkenazim. However, these data must be interpreted with caution as they assume the penetrance of the BRCA1 to be the same in minority patients as they are in Caucasians. In addition, there is no analysis of BRCA2 carriers. But this is a great starting point.

Saturday, December 22, 2007

deCODEme results, Thanks Med-Source!

The Sherpa Says: Thanks to Megan for publishing this to the web. I am certainly interested in the medical aspects of these companies. Being pragmatic is different than being skeptical. I am both. Thanks to my other pragmatic skeptic Dr. Colby for pointing this video out for me.

Friday, December 21, 2007

Warfarin rears its ugly head

I swear I have seen more intracerebral hemorrhages from Coumadin in the last year than in the any of the literature stating it's incidence. Last night I admitted an elderly gentleman who was in his usual state of health until he slipped on the ice and bumped his head. He then carried about his business for a day and a half. Then as he went to work his secretary noted him acting unusual.

When he showed up in my Emergency department, he had an INR of 9.4

For all of those who don't know what an INR is, 1.0-1.4 is normal. This is abnormal, big time.

He had traditionally been on a very low dose of coumadin (I.E. poor metabolizer) The problem was not that he just had very thin blood, the problem was the huge bleed he had in his brain!
What can we do about this problem? I have mentioned the future of coumadin therapy several times. I was just speaking to Dr Isadore Rosenfeld yesterday who pointed out to me that a recent study once again shows how beneficial Warfarin is in preventing strokes caused by a condition known as Atrial Fibrillation. The incidence of Atrial fibrillation increases as the population ages. Therefore, I am certain that we will begin to see more poor metabolizers and even more poor outcomes.
The Sherpa Says: On Coumadin? Mind your INR? Starting Coumadin? Get your metabolizer status checked! If you are in NYC or Greenwich come see us. Thank you to GTO for the early Christmas present....

Wednesday, December 19, 2007

Genomics Into the New Year

What will the New Years bring genomics. Well, I have had my ear to the ground and have some ideas.

First the obvious
1. GINA will be passed by hitching a ride on another bill. How sad is that?
2. Navigenics will enter the fray and telemedicine will have a whole new face. What that face will look like is yet to be completely determined.
3. One of these companies will get sued

Next the less obvious
1. Academia will start to market personalized medicine
2. Helix Health of Connecticut will not be the only face to face private (non-Academic center) personalized medicine service...and they will be welcome friends. There are so many out there who need this.
3. Oprah will have her Genome sequenced ( I swear it will happen)...Obama too

Finally the inconceivable
1. Jim Watson will pass from this earth
2. A little unnamed startup will win the X-Prize
3. Mark Cuban will buy the rights to all of 23 and Me's genome database

The Sherpa Says:
To know the future we must look at the past. And if we fail to learn the mistakes from our past, we can always blame our genes. Or at least have the journalists tell us we can.

Saturday, December 15, 2007

Not Again OMG UK!

In another amazing step towards eugenics. Britain has awarded a couple the right to prenatal test for familial hypercholesterolemia. This way they can then terminate a pregnancy that may results in a child plagued with the disease of high cholesterol and heart attacks. In the Times

FH occurs in two forms. The more common version, heterozygous FH, affects 1 in 500 people. It is caused by a single mutated gene, which raises cholesterol and thus the risk of hardened arteries, heart disease and stroke. It can usually be managed with statin drugs and diet.

Britain’s first licence to test embryos for FH will be awarded next week to Paul Serhal, of University College Hospital in London, by the Human Fertilisation and Embryology Authority (HFEA).
Its decision breaks new ground because it permits Mr Serhal to screen out not only the severe form of the condition but also the milder type, which is usually treatable.

In addition this brings the thought of pre-implantation genetic diagnosis (PGD) for the disease. I know many people who are heterozygous for this disease. I treat them with cholesterol medications. Do I tell them they could have PGD? No. Do I tell them that their children will be at risk for heart disease? Absolutely. Is this a treatable condition? You bet. Can it be devastating? Yes. Does that mean we should PGD every gene you may not want? Hmmm this sounds familiar.

So where do we go from here? Gattaca.

Well, this certainly is a slippery slope. Let me know your opinion. This Times readers opinion says is very nicely

Lucky for us that the parents of (Agatha Christie - Alfred Lord Tennyson - Algernon Charles Swinbunre - Blaise Pascal- Charles Dickens Dante - Edgar Allen Poe - Edward Lear - Fyodor Dostoyevsky - Gustave Flaubert - Guy de Maupassant Lewis Carrol - Lord Byron - Professor Manning Clarke - Pythagoras (Philosopher & Mathematician) Sir Walter Scott - Socrates - Truman Capote) weren't tested for Epilepsy. Our world would be a much less interesting place.
Martha Ware, Hammonton,NJ, NJ/USA


Friday, December 14, 2007

Education Initiatives

I have been sick with a nasty virus this week. Vomiting has been the order of the day....yuck :(

Because of this, I will keep this post extremely short but useful. The SACGHS meeting was held last month and I think it was huge. There are a lot of good webcasts that are a must watch.

The rate limiting step of personalized medicine is physician uptake, and the rate limiting step in uptake is education. The SACGHS meeting on the 20th of November was huge reviewing efforts and ideas for education

Overview of Session
Barbara Burns McGrath, R.N., Ph.D. Research Associate Professor at the University of Washington School of Nursing. She reviews nicely the outline for the day and gives us a guideline.

Please check out the lecture given by the National Coalition for Health Professional Education in Genetics Executive Director. He describes a database similar to the one we are working on.

In addition, we need to utilize physician extenders. The advantage of having nurses in genetics is the fact that they have had some education in medication dosages and medical conditions. The same applies for physician assistants in genetics. But they will never replace the counseling abilities of professionals who have trained for 2 years in the field of genetic counseling.

Elizabeth Pestka, M.S. Assistant Professor of Nursing at the Mayo Clinic College of Medicine describes the 80 or so nursing organizations. It turns out 40 of those, 50% agreed to help include genetics into the nursing competencies. In 2006 there was a meeting to implement these competencies into practice.....This is where I sat back in awe. It is 2006 and they are just getting around to integrating these competencies? We are screwed for the next 4-5 years! But it turns out according to Nurse Pestka that these proceedings often take up to 17 years to become integrated!!!

I have worked with a nurse geneticist at Yale and I have to tell you how wonderful it is to share call with a nurse practitioner who is trained in genetics as well. I think we can really leverage our efforts with these talented individuals....I hope it doesn't take 17 years!

The Sherpa Says:
Now if we can only train genetics counselors in medicine!!!

Thursday, December 13, 2007

Wall Street Journal Agrees....We Need More Sherpas

In the WSJ today and also on GTO it seems we have a common theme. Something perhaps that I have been saying all along. It is nice to see Gautam agree with me....

From the Article:

Ever since the human genome was deciphered seven years ago, companies have been rushing to sell genetic tests directly to consumers. But buyers, beware: Many of the claims that accompany these tests are not fully supported by science.

Read my post about it

deCODE genetics' test for a gene variant linked to Type 2 diabetes: Some research says the predictive value is weak....

"The predictive value of the genetic test is pretty poor," says David Melzer, a professor of epidemiology at the University of Exeter, England. Last year, Prof. Melzer and colleagues published a study based on data collected from more than 900 elderly people in villages near Florence, Italy. They found that 80% of the people who tested positive for TCF7L2 didn't get Type 2 diabetes in old age. And nearly 40% of the people who had diabetes didn't carry the gene variant at all.

This One Too...

"The significance of the risks uncovered by these tests is very, very small," says Stuart Hogarth, a fellow at the Institute for Science and Society at the University of Nottingham, England, who has studied the genetic-testing industry. "Commercialization of genetics tests at this stage is premature."

Oh I think I said this too.....Twice

Let's chalk this all up to media hype...Or the lack of appropriate medical knowledge to combat the hype

"The Sherpa speaks the language of the trail, he/she knows short cuts and dangerous paths to avoid."

I hope I have served my readers well.......I know my Helix Health of Connecticut has.


Wednesday, December 12, 2007

Toxic Epidermal Necrolysis and Pharmacogenomics

For those who don't know what TEN is. I have a picture for you.
Toxic epidermal necrolysis (TEN) is a clinical syndrome characterized by severe exfoliative skin changes, erosive mucosal involvement, and potentially life-threatening multisystem involvement. Although this syndrome is considered uncommon, its true incidence may be underestimated because of a spectrum of manifestations that may lead to misdiagnosis of milder forms of the disease. TEN most commonly occurs in adults and is seen slightly more often in females. All races are affected
Yesterday, the FDA issued guidance for pharmacogenomic testing of patients taking the medication carbamazepine. What is this drug? It is used in prevention of seizures treatment of mood disorders and schizophrenia.
More than 100 drugs have been implicated. Medications most often involved are systemic sulfonamides and other antibiotics, allopurinol (Zyloprim), antiepileptics, and nonsteroidal antiinflammatory agents . The time from the first dose of a drug to the first cutaneous manifestation is usually 1 to 3 weeks
This medication has now been flagged as a cause of TEN that has preventable testing. In addition to the novel testing of an HLA haplotype, the drug is metabolized by CYP 3A4. CYP testing is available for ultrarapid metabolizer status. However, that is not what causes TEN. No one knows exactly what causes TEN for sure.
But the biggest problem is the 30-40% of people with this disease die from it or it's complications. Now wouldn't it be great if we could at least test a sub population at risk for this before giving this medication?
We can. From the FDA
Significantly more common in patients with a particular human leukocyte antigen (HLA) allele, HLA-B*1502, this allele occurs almost exclusively in patients with ancestry across broad areas of Asia, including South Asian Indians. Genetic tests for HLA-B*1502 are already available.
The Sherpa Says:
Ladies and gentlemen, I submit, we are now moving in to the era of personalized medicine. This test is yet another example. If 2007 was the year of the personal genome, I say 2008 will be the year of the personalized medical care. I hope that we can accurately represent the utility of these services. Wingedpig once again comments on the shortcomings. Also, where are the BRCA SNPs? Has Myriad's attorneys knocked on 23andMe's door yet?

Tuesday, December 11, 2007

23 and Me and You, On a date!

Another Day, Another Genome Scam!

For 2000 USD, you too can have a date with DNA!

The Boston News covers a little known start up called
Cute name I know. Total ripoff...I know

The Guy at the end of the news broadcast says it all. BTW the scientific data which this guy uses is so bogus that I will not talk about it. But you can take a look at it here.

The Sherpa Says:
This is so sad that I don't know what to say......

Monday, December 10, 2007

Jason Bobe is a tremendous writer.

When reading blogs all the time. Well, not all the time but the 5 minutes in the AM and the 20 minutes I have each night. I continue to be amazed by the breadth of knowledge that the DNANetwork has. In addition, I am blown away by the writing ability of some.

The person who I bring to your attention is Jason Bobe over at The Personal Genome
Here is a snippet of what he pens (types)

The era of personal genomics will transform our notions of risk in many ways. In the realm of health and medicine, we will soon have much more specific information about our baseline risk for a health outcome, such as a disease or a pharmaceutical drug response, and how it is influenced by our DNA and modulated by other factors like physiology, lifestyle, and environment. At some point, we will have health risk profiles that prioritize and sort risks according to severity, immediacy, and whether effective strategies are available for managing them with pharmaceuticals, lifestyle modifications, or other medical interventions. There might even be a richter scale for genomics one day. This vision of the future is often referred to as “personalized medicine”.

Succinct, Explanatory, Brilliant if you ask me. He wonderfully explains a topic and breaks it down nicely. He brings issues to the forefront and posits answers.

I wish I had more time. I was invited to participate in Second Life. I would have loved to. Unfortunately I am too busy to have a first life....If you get the chance check out his recent post on virtual conferencing.

Lastly I want to point you in the direction of the SACGHS. If anyone has a big say in how the government will set up personalized medicine, it is this group. I have told you before about how they advise the Secretary of HHS. There latest meeting was last month and I am digesting all the data. Stay tuned.....

Sunday, December 9, 2007

Algorithms and Validation

A friend of mine asked me "If the framingham risk assessment fails to take family history into account, then why do we use it to guide anti-cholesterol therapy?" My answer was "It is scientifically validated."

In medicine we like to do things based on evidence. It is true that we do many things that do not have solid evidence behind them. But we always try to acquire data and then make a rational conclusion, leading to a treatment. When it comes to risk prognostication, validation studies are extremely helpful. And often keep us from getting sued.

So what did the Framingham do to be validated?

The Framingham Heart Study and the Framingham Offspring Study were the first epidemiological studies that prospectively collected population based data on the association between risk factors and the occurrence of fatal and non-fatal coronary and other cardiovascular events in a systematic and sustained fashion. It has been dissected for it's validity over the years.

So can we use the Framingham for everyone? Well, in Europe they tried. Several articles like this one show that the risk tool must be validated in the population you plan to use it for. The Framingham doesn't work so well on the Dutch. However when modified by the REGICOR, Spain's NHLBI, it seemed to perform well for the Spanish. The same with the Chinese modification.

You may now be asking what the heck does this have to do with Personalized Medicine. My answer....Everything. You see part of personalized medicine is prediction. That's why Helix Health of Connecticut trademarked "Prediction, Prevention, Privacy" These are the pillars of genomic medicine.

How can you predict the likelihood of Alzheimers in 5 years? Well, there are some corporate genomic companies doing it without having ever submitted articles for peer reviewed publication. They have "Trade Secret" algorithms that calculate risk. What the hell? How can you trust the accuracy of an algorithm without validation?

This is why we advise against using the Gail model for breast cancer risk. It can only work for certain populations, absolutely not for African Americans. There are new attempts at this type of risk stratification, and several attempts to defend the Gail model. But what has evolved is even more important. New algorithms...that were put to the test and peer reviewed.

Which brings me to my last point. What good is a tool if you don't know how to use it, or who it works for? A recent post on Wingedpig points this out. Confusion as to the tools. But what I wonder is what tools they used to create the tools. Would they publish their algorithm? Should they have to? Should other companies who will foray into medicine have to? As for SNPedia...a great resource, but the results are just like a wikipedia....not exactly peer reviewed.

The Sherpa Says:
The votes are in. I am surprised of the results. 23 and Me is the big winner. Why? Well, they specifically state that they do not intend their tools to be used for medicine. Yet all the posts I read have authors who mistakenly are using it as a medical tool. (See the genealogists post "when will they learn") I would have thought the readers would have chosen Navigenics. Navigenics WILL use their tool as a medical device! So I have to ask them. Where are your data on algorithms? Where did you publish and validate them? Which algorithms are you using? I guess we will find out soon enough. 2008 is right around the corner.

Friday, December 7, 2007

Genetics Depression and PGx

In case you have missed it. There will be an excellent talk given at the National Press Club in D.C. I will be sending members of my team to these lectures on the broad policy issues emerging from growing understanding of the genetic basis of depression and other mental conditions, the ability to detect genes responsible for these conditions and offer therapy based on genetic tests, and the policy questions raised more generally by genetic testing for personalized medical treatment.

To register for the talks check out the Genetics and Public Policy website. Which brings me to my next topic.

Genelex now has a blog. For those who do not know who Genelex is.....

From their website:

  1. Nutrigenomics

  2. Ancestry Testing

  3. Paternity Testing

  4. Pharmacogenomic Testing

Why is this company offering all this testing? Because they can. They have dipped into every market....well almost.....No Genomes here! They have a solid reputation for results. Whether you can utilize them or not is a different story. But nonetheless they are a very reputable testing company. I am surprised that they aren't doing genome sequencing as well...

Has anyone read what the Economist has just published re:corporate genomics?

"Moreover, physicians' calls for scrutiny should themselves be scrutinised, because genetic testing inevitably transfers power from doctors to laymen.
That transfer of power brings responsibility, of course—the responsibility of consumers, aided by the gene-testing companies themselves, to interpret their new knowledge sensibly. If they do not, doctors' surgeries may be flooded with what have come to be known as the worried well, and regulation is sure to follow. If people do take responsibility, however, a healthier life awaits them."

The Sherpa Says:

How can we expect to have laypeople take responsibilty when the medical education community has turned their backs on this field for the last 50 years? How long does it take to make a medical geneticist? 4 years of undergraduate work + 4 years of medical school + minimum 4 years of postgraduate residency = 12 years. Does the layperson need 12 years of study? No. But one year is a minimum.....I hope you agree. BTW there are 2 days left to vote for who will get sued first. It's pretty clear 23 and Me is in the lead.

Wednesday, December 5, 2007

Delaware Reducing the Gap!

As I had talked about in prior posts Coriell has now officially launched the Delaware Personalized Medicine Project. For all of those genome seekers out there, I suggest that you check out this project.

Who is Coriell? Well in case you have never heard of the HapMap before today....

The Coriell Institute for Medical Research is an internationally known not-for-profit, basic biomedical research institution. The Institute's founder, Lewis L. Coriell, M.D., Ph.D., played a major role in bringing the Salk polio vaccine to the public by using cell cultures to study human viral diseases. The Coriell Institute was founded in 1953.

I initially had contact with the people from Coriell in 2005 at ASHG. This is an amazing group of dedicated individuals who are always carrying genetics forward. The Repositories at Coriell provided support to the Human Genome Project, a world-wide program to map the entire human genome, and to the International HapMap Project, a project to provide an efficient tool to identify disease causing genes.

The Delaware Valley Personalized Medicine Project© is a forward thinking, joint effort involving patient volunteers, physicians, scientists, ethicists and information technology experts whose goal is to better understand the coming impact of genome-informed medical practice and to guide its ethical, legal and responsible implementation.

The study will seek to discover presently unknown genes that elevate a patient's risk of cancer, heart disease and other complex diseases, to understand why patients often respond quite differently to treatments, and to explore how the resulting information can best be viewed and utilized by patients themselves and their physicians in a secure, user-friendly environment.


All patient volunteers will control their genetic profiles and will be able to determine for themselves whether they wish the information to become part of their personal medical records in the future.

The First Volunteer? A South Jersey Congressman....Maybe they can find the "Crooked Politician Gene"......Just Kidding....sort of :)

The Sherpa Says:

This is exactly what the field of Personalized Medicine needs. Not some project hidden behind fancy marketing and a cool website....or 3 million dollars of seed capital. This project will allow you total control over your genetic information and that is precisely what the public needs. I feel sorry for those who paid to have their SNPs resold at a higher price.

Family History Tidbits

In my search for useful news today, I have come across something near and dear to my heart. Karen Lu at M.D. Anderson has posted on the importance of taking a family history. Her spin is obviously tilted towards cancer, but the benefits of family history or just as important in diseases like heart disease.

From the site:

“Family gatherings are the perfect time to ask family members detailed questions about their health history,” says Karen Lu, M.D., co-medical director of the Clinical Cancer Genetics program at M. D. Anderson.
“It is important to gather information about the health history of your parents, siblings, grandparents, aunts and uncles, and even your cousins.”

She points out that there are some red flags to watch out for in your family.

1. Early onset of Cancer. (I say not only cancer, any disease is important here)
2. Family member with 2 or more "related cancers" (These include things like breast and ovaries. For more info see here)
3. Two or more family members who have related types of cancers. (Too bad some insurers require 3 members to be afflicted in order to pay for BRCA testing)

If you find some of these red flags you should at a minimum ask your physician about genetic evaluation. If you live in the CT, NY, NJ area give Helix Health of Connecticut a call. Genetic Testing may be appropriate for you and evaluation is needed.

Genetic testing involves looking for abnormal genetic changes in a person’s blood sample. People who inherit abnormal genes from a parent may be at increased risk of developing cancer.

“The benefit for the cancer patient who tests positive for an abnormal gene is that doctors can use this information to determine if they are at increased risk for a second cancer and to help family members,” says Molly Daniels, a genetic counselor at M. D. Anderson.

For family members, the benefit to learning that a close relative carries an abnormal gene is that they too can be tested to determine if they are at increased risk for developing cancer.

Those who test positive may begin routine cancer screening exams at a younger age than what is usually advised for the public. High-risk screening enables health professionals to detect cancers as early as possible when there is the best chance of successful treatment and cure. Those who test negative can be reassured that they are not at increased risk because of family history.

The Sherpa Says: The major risk factor in both heart disease and cancer is family history. Perhaps more so in heart disease. Evaluation for these risks need to be done on an ongoing basis. Remember, your family history changes with time. So if you have taken your family's history, up date it yearly or when something you know has changed. A great tool for this is found at the HHS website!

Monday, December 3, 2007

We need more Samples/Sherpas!!!

Genetic Research is a hard business. You have to fight and IRB to get your I's Dotted and Your T's crossed. You have to write and write and write grants to get funding for your ideas. You have to manage the project and work to keep everything on track. But what will the rate limiting step be in genomic research?

Perhaps it is the lack of samples?

From Medical News Today, an exciting announcement regarding Lupus. Lupus is a terrible disease where the immune system attacks the body's DNA. It can cause horrible things including, stroke, skin disease, kidney disease, brain inflammation. In fact a whole host of persons who have this disease are unable to function in society.

A new finding includes the discovery (Not Validation) of a gene implicated in Lupus' pathogenesis (disease cause) OX40L. These researchers have identified other risks as well. His findings are only mildly interesting as replication will be needed. But what is more telling is his plea to the British people

"Without DNA samples from people with Lupus, we would be unable to study the disease," he says. "Despite the disease being relatively common, DNA samples are in short supply. I would encourage patients to discuss with their GP or consultant about providing a blood sample to help further our understanding."

With all of these companies looking at your SNPs or your Exomes or your Genomes and the vigor with which they launch PR campaigns. One would hope they could donate their datasets to these Scientists in need.

I perosnally have been trying for months to help a friend donate her genome to a sequencing project. Hope fully the Delaware Valley project will take her code. I think that genome sequencing will ultimately win the day over some of this SNP Chip technology. Why? SNPs are not enough. Copy Number Variation will slowly be found to play as large a role...if not more. You can read about some of this here.

The Sherpa Says: Did anyone watch the 60 Minutes special on Sherpas in The City. Turns out that for their health Sherpas are moving to New York. Any Gene Sherpas in the batch? I sure hope so. The Gene Sherpas of the world are coming together for one big collaboration and I can't wait till we all can guide the genomic tourists of the world!!! Stay Tuned for the Sister services soon to show up on the scene. Heads Up L.A., S.F., CHI!!! Are you a Sherpa? Want to join the team? We would love to have you. Can't wait to see you all in NY!

Friday, November 30, 2007

Maybe I am wrong...

So after talking with a pretty amazing reader today. I was brought to some interesting conclusions. The first of these.

1. Maybe Corporate Genomics is not so bad after all.
I know...after all this must begin to say. "Is this Sherpa crazy?"
No, this is a critical assessment. What is the risk of using these services? Discrimination? Well, health insurance discrimination is a fallacy. Very few employers have discriminated genetically.
Changing a behavior to a more deleterious behavior? Well, the McD's fries might get eaten more often if you don't think you are going to get heart disease is a reality. Will this set of tea leaves be perceived as strongly as a physician's interpretation? Or will this get treated like it is......a suspect set of data. That is the real question. If the answer is that the public treats the computer the same as the trained professionals, then we will have true risk. This has not been proven yet. Nor has the benevolence of these companies. But I can't say guilty until proven innocent. Especially because I have 10 readers from Mountain View daily (on average)

2. Maybe Primary Care Physicians can learn to perform genetics
Huh? I know. I have data which states that it takes more than a year to learn these topics. But, I don't have data for year 2 yet. Maybe in year 2 we see a tremendous uptick in knowledge and skills. Maybe not. But, I cannot make sweeping claims without this data.

3. Maybe Google, Kleiner Perkins, Genentech, NEA are in this for the benefit of mankind.
Ok, now I am strecthing. But maybe they are? Google has been investing in earth-friendly companies, education companies....KP is investing in Personalized Medicine, We know how Genentech has revolutionized some parts of medicine.......

You see. Socrates is correct. We need to challenge that which is taken as fact.

The Sherpa Says: Doctor Oliver Wendell Holmes said "Man's mind stretched to a new idea, rarely takes it's original form" Maybe I am wrong.....Maybe I am not.....But you have to take both as possibilities.

Thursday, November 29, 2007

A little Knome fact!

Well, after fighting to keep the name Helix Health of Connecticut. I have realized that just because you have a catchy name does not mean someone else doesn't have it too.

Thus is the case with Knome. I could ramble on about how whole genome sequencing is superior to the limited SNP analyses currently available. This superiority is very important for personalized medicine, but not quite important for a cocktail party. I could have posted some of the press release, but Hsien, Berci and the rest of the DNANetwork do a great job of covering this sort-of new entry to corporate genomics.

Instead, I wanted to focus on the fact that another Knome exists. In fact several Knomes exist. Some even have vice-presidents. Well it turns out Knome has been around a little while before this. In fact a company called Cambridge genomics has filed an application for trademark of the name Knome in August of this year. Smart, unfortunately I did the same thing and have met challenges. Well, they should be ok, so long as their aren't any other software apps out their with knome in their knome...oooops

The Sherpa Says: With the decreasing gene count, clearly the secrets in the genome lie in other places. These include copy number variation, methylation, and other epigenetic changes. You see, the genome is constantly in flux and change. This is why a genome without a solid knowledge set behind it is as useless as a map without a key. But it's just about as much as 2 Ferrari F430s. Living in Greenwich CT, believe me, I have seen my share of his and her Ferraris. Why not his and her genomes.....What a great Christmas present for the person who has everything else, including 17th Century Samurai Swords...p.s. Why hasn't anyone mentioned SmartGenetics yet?

Wednesday, November 28, 2007

Aetna and Informed Decisions

Amazing today I have had to make the time for a second post. I received an email from Heather L. Shappell, M.S., CGC. She is the founder and COO of Informed Medical Decisions, Inc. The newsworthy event is that they have partnered with Aetna to delivery informed consent for genetic testing for cancer.

What is this company? Well......

From the site:
Informed was created to increase access to experts in cancer genetics for people at risk for hereditary cancer. Genetic counselors help people and their doctors make the most informed genetic testing, cancer screening, and cancer prevention decisions

This is precisely what they are now doing.
From the press release:

Aetna (NYSE: AET) today announced that effective immediately it will offer members confidential telephone and web-based cancer genetic counseling services as a component of health benefit plans which include coverage for genetic testing. The services will be offered through Informed Medical Decisions, a national genetic counseling company staffed with board-certified genetic counselors with expertise in cancer genetic counseling.

The GTO has also just put this on their post. I feel bad replicating data, but there are some people who may not get the GTO newsletter. If you don't, your missing out.

The Sherpa Says: Telegenetics has been around for a while. The Military has been using it and there are places such as Harvard which are trying out video genetics. It is a shame that their are too few people in the field. I think that Myriad is actually helping out physicians with this task. However, a word of caution. According to my research.....the more confident a non-genetics physician is at counseling, the less likely they are to do well on a genetics knowledge test. This is where Informed comes least for cancer counseling....To do more than that you need more
Although this sounds great it is too bad Aetna has one of the most retrictive testing policies for BRCA out there....

4 days too long!

I have had to sit out of the blogging game for 4 days. This was a self imposed punishment to help me get re-oriented. I have been working hard on the practices and have been talking to many different people about our next steps. So I apologize.

There are some neat things going on in the field of Personalized Medicine lately. My old friend The Mount Sinai Hospital will be offering CYP 2C9 and VKORC1 testing for Warfarin dosing. This is in addition to the other corporate labs which are already offering it, such as LabCorp, Kimball, Genzyme....

Why? I think this is part of a greater play by academic centers. Notably, Mt Sinai has a Institute of Personalized Medicine. This department was endowed by Samuel Bronfman's Philanthropic Arm. They have a mission which is to bring personalized medcine research to a point where it is ready to launch.....

They are also setting up a bio bank, offering money for people's genomes. Sound familiar? I had just talked about 23andMe possibly using their data in a similar way.....Except the investigators would be making money off of the research subjects...

Here's the difference....The Mount Sinai School of Medicine will be doing research on their own. Notably they have been doing it already. Despite some scuttlebutt about turf wars at a big institution they have started to play nice in the sandbox and put out some good research. This article I find especially timely. we have always known that genotypic variation plays a role in the metabolism of certain drugs. In this case, 2D6 metabolism has an even more important in the Ashkenazi Jewish. Here they find twice as many persons af Ashkenazi heritage have ultrarapid 2D6 metabolism. This enzyme is the key player in many psychiatric medications....

The Sherpa Says: I am absolutely certain that ethnicity will play a huge variable in the frequency of these ultra-rapid metabolizers of any medication. Pharmacogenomics may be meeting genealogy sooner than we think....Thanks to Sherpa Hsien for helping me with a SNP issue the other day......

Saturday, November 24, 2007

Minding Shop

With all of this hullabaloo about genome sequencing companies and what they might do with your genome, including possibly selling the "de-identified" data to pharma companies. A great business plan, but NOT personalized medicine. I actually received 3 emails pointing out the same idea. I do know a friend of mine who sold his plasmapheresis company to the British Government, not because of the need for products in the UK, but because Bayer was this company's biggest customer.

So the whole selling data/product to pharma is a plan which can make tons of money. Which could be the reason why the"genome" service is so cheap. Last time I checked, the best bet at the craps table is the pass line, provided you are on a come out roll. It's the proverbial hook.

With that being said, I want to come back to personalized medicine and a recent study published in the American Journal of Human Genetics in the December issue. We frequently counsel patients that BRCA positivity does not mean you will absolutely get breast cancer. In fact the likelihood is less than 90%

So what modifies this risk? Well, we know for certain of 1 gene called RAD51. This gene interacts with the BRCA genes and is required for a certain type of DNA repair, known as recombinational repair of double stranded DNA breaks. It is known to predispose patients to a blood cancer called AML.

To investigate the role of RAD51 common changes/SNPs in the modification of BRCA risk, these researchers investigated the results of 19 studies from very diverse populations. The results were decent. Not a home run per se, but they gave us some insight into the roll of SNPs in modifier genes. The study indicates that your risk for BRCA related breast cancer is increased with a SNP called 135 G to C.

The carriers of two copies of this change have a 3 fold increased risk if they are BRCA2 carriers. The increase 2 fold for BRCA1 carriers. Which brings me back to my interview with Bertalan Mesko at Scienceroll. The world of personalized genomics is here, we now have the tools to say why 100% similarity in expression. So what's next for this finding? Maybe it will find its way to an Illumina of Affy Chip? This certainly would be useful information prior to prophylactic mastectomy......

The Sherpa Says: Ahh, it feels good to tell you about data leading us up to the personalized medicine revolution. We must not take our eyes off the prize here. Party tricks with an algorithm not validated is NOT personalized medicine. But the results of this study once further replicated could be. Imagine reflex testing for RAD51 SNPs after you have the BRCA results. This could put the decision process into a less ambiguous path.

Thursday, November 22, 2007

Giving Thanks

In the US, today is Thanksgiving. A day where family and friends come together and appreciate what we have. We consume massive amounts of food, drink, some smoke, and not surprisingly get admitted to the hospital the next day.

This year I would like to offer up the one healthy thing you can do. Take your Family History. Started in 2005, the Surgeon General has named today, National Family History Day. So visit the HHS website and find out who has what, who died, how may end up saving your life. When your done and if you are concerned about it, Come See Us! We even do home visits!

The Sherpa Says: Happy Thanksgiving to all. Today I am thankful for YOU, my readers. Have a great Holiday!

Monday, November 19, 2007

Staying Positive

I was showered with a host of emails from my readers today. The GTO highlight, The Issue feature, Scienceroll's commentary all the readers had to say one thing. Sherpa, take it easy. You beat up on DNADirect and their questionable questionnaires, You picked on Forbes giving hype to deCODE, You pointed out that Navigenics had some sketchy ethics, Slammed Salugen, Attacked Myriad, and Now little 'ol 23 and Me. Did you have to sink this low?

Sink this low?

Wow! Ok, so I have been known to blow my top a time or 2. Can you blame me? Have I stated any incorrect facts? Maybe some, which I have quickly amended. Including the fact that DNADirect does not "mark up" test costs. Even though I am still unsure of how a company who sells tests at cost and charges 75 USD for phone consultation (even less than an academic center that is losing money on counseling pays a genetic counselor) makes any money.

So why did my readership feel this way? The answer. "Why won't you endorse us using suspect science data to give us suspect risk assessments?"


Yes, it is true. Even the educated are intrigued by this little black box known as the Gene Journal and Risk calculator. Fine, I like the magic 8 ball too. So here it is. I am putting it on the record. I will not hate you if you use 23 and ME. In fact, I suggest you use it after taking a family history and having the familial risks evaluated. If these SNPs give you more insight than a family history....I applaud you. Here's my last appeal, please realize that this data will not be considered medical records if you use a non-healthcare company to screen your genome.

If you want the BEST coverage, you should use deCODE, 23andME, AND Navigenics services. This is the only way you will get ALL the SNPs your little lemming heart can desire.
Then, when you want to make your genome a medical record and protect it, ask your physician to review the data. If they rebuff, go see a geneticist. Helix Health of Connecticut can interpret the SNPs in concert with your family history. Your Genome In Context........ ;)

The Sherpa Says: Please don't hate me for the aggressive commentary. I am not a hateful guy. I just call it like I see it. Maybe you see it differently and that's the great thing about the Blogosphere. Different viewpoints, Different ideas, The Same Passion.

Sunday, November 18, 2007

Who Needs Institutional Review Boards?

From Wired Magazine, a quote from Anne Wojcicki regarding her Gene Journal and risk calculator

"A lot of this is unknown. It's totally experimental," Wojcicki told me a few weeks before the science board meeting. "No one has looked at all eight diabetes markers together. They've all been identified individually, but they don't know exactly how they work together. So we've tried to make that clear."

To crunch these numbers and determine one person's risk factor, 23andMe has opted to multiply the risks together. But a competing school of thought argues for adding the risk from SNP to SNP. The two approaches can result in wildly different tallies.

Welcome to the first Google driven experiment in genetics, paid for by the customers......

Unfortunately that poor author from the NYT demonstrated her clear lack of that understanding. And she is a learned journalist, what's to happen to the layperson who has never had any education in genetics/science? Well, I guess you have to break a few eggs to make an omelet....... Primum Non Nocere....oh wait, I forgot, Anne isn't a physician...

The picture here is that of the Tuskegee syphilis study. A horrible experiment carried out on unwitting subjects that sparked the founding of Institutional Review Boards. IRBs were formed to protect research subjects. Why could Dr George Church only get a select few for his first personal genome project? The IRB deemed laypeople unable to give informed consent. How did they end around the IRB?

23andME "Genetics By Businesswomen"
The Mission? Mission Statement
23andMe's mission is to be the world's trusted source of personal genetic information
The Sherpa Says: Keep evading laws, it's the best way to gain my trust.

Saturday, November 17, 2007

Not with a Bang...The Death of Personalized Medicine

Today I plan to discuss where this magical field of personalized medicine is headed. A few things have changed over the week, and I think that this may change what I was originally going to discuss. But all in all the likely paths of personalized medicine could be up to 8-fold. Some are less likely and are therefore not discussed here.

In order to really understand personalized medicine's future we must know 4 truths.

1. Genotyping is getting cheaper and cheaper. Less than a penny a base pair. So in turn genetic testing should get cheaper and cheaper. This is the idea of a 1000 USD whole-genome. Unfortunately some tests still remain in the thousands of dollars. Therefore, I assume (unless these companies are paying their workers millions), that there is some significant money being made here.

2. There is a lack of healthcare specialists trained in the field of genetics. In fact the healthcare system fails all of us when it comes to genetics education and understanding.

3. The alternative healthcare market is skyrocketing. Do-it-yourself (DIY) treatment with herbs, vitamins, and nutraceuticals is predicted to be a trillion dollar market in the next decade. As a corollary, because genetics is not well understood by the "standard" medical practitioner, many view this as an alternative healthcare style

4. Insurance reimbursement for even standard genetic tests and counseling is woeful. If you are with an insurer such as Empire BCBS coverage of a BRCA panel is limited only to those who have breast cancer, or those who have 3 family members with such cancers at frighteningly young ages. This is better than others, who flat out refuse to cover BRCA testing unless a letter of medical need is written(taking valuable time from genetics providers).

This leads me to the paths. I think the paths are reliant on 3 things

1. Legal issues such as GINA approval and legal requirements changing for genetic testing

2. Public opinion for genetic technology in medicine remaining favorable

3. Personalized Medicine not being oversold

Probable Path 1

GINA is passed and states continue to have strong laws regarding genetic testing .
In this environment of protection from discrimination, polls have already demonstrated that the public will continue to view genetics as good for medicine. Therefore there will be a market for personalized medicine services. Private and public investment will continue to fuel the machine. However,there will be significant legal challenges to non-medical providers offering genetic services. But, personalized medicine will thrive. Discovery will continue and the public will continue to be excited. Personalized medicine will start to be oversold and the public may go wary. We are already seeing these trends with companies such as Navigenics. If lawsuits should happen, and they will, private investors will back away from this potential landmine

Probable Path 2

GINA dies in the Senate and strong laws regarding genetic testing continue to be enforced.
In this environment the public will still continue to be wary about discrimination. Most will not see value in giving a company, not governed by HIPAA, their genomic information. This is the environment we currently are in. All of this investment in these genome sequencing companies can go awry if customers’ personal health information can be sold to marketers looking to personalize ads. In addition if the government wishes to investigate DTC companies, as it is currently doing in CT, private genome sequencing could be a fad like Z-Cavaricci’s. Cool to have for a little while,until you realize that they put you at risk of being ridiculed or discriminated against. Now smart ad people will tell you that it is worth the risk, they may even tell you “Why not have the data now? You can use it later, but why not buy it now? Everyone is doing it.” Until that first case of genome data showing up when your prospective employer googles you. I imagine that would be worse than those “party” photos you still have up on your MySpace site.

Probable Path 3

GINA is passed and laws relax on genetic testing
In this sweet spot for corporate testing we see the rise of consumer genomics. The public opinion views this technology as benign as pregnancy testing. This is a scenario where the movie GATTACA takes place. “Genetics as a tool for better living”. Fueled by investment the future of personalized medicine is strong. We will see sex selection, PGD for athletic abilities. Since employers cannot discriminate based on “genetics” we may see some lawsuits because of genetics being used as a surrogate for “abilities” Because of the lack of legal consumer protection, the overselling may end up killing the best parts of this field. The databases of genomic data for research will be overflowing as patients will have no fears. IRBs will not have to treat genetic data and differently and perhaps restrictions on genetic research will be reduced. Discovery could be enhanced in this environment. I can see why many PhDs would favor this scenario.

The Sherpa Says: There are many more paths mapped out in my mind. I, the Sherpa have envisioned this mountain for decades. This is my passion. My existence. Maybe you should ask your friendly neighborhood consumer genomics company if it's theirs too. One things for sure, overselling via the NYT, Forbes and 23andMe will kill any chance of personalized medicine being viewed as a credible, respectable, medical specialty. This could be the beginning of the end of personalized medicine!