Thursday, May 31, 2007

Tuberculosis, XDR-TB and Personalized Medicine!!

After all the talking and pundits, after all the media hype and fear. XDR-TB still remains a serious issue. True there seems to be significant irony in this case and that may make it stick around a while. What is XDR-TB? Well according to the CDC

"Extensively drug-resistant (XDR) TB – or TB that is resistant to at least two main first-line drugs (Isoniazid and Rifampin) and additionally to three or more of the six classes of second-line drugs"

So why post about tuberculosis in a personalized medicine/genetics blog? The answer is simple. There must be something in the genetics of host or bacteria that create this resistance. In addition there must be a way to test for these and prevent inappropriate treatment.

This treatment is dangerous at times even causing hepatitis and liver damage. A certain subset of people cannot handle isoniazid at all. These people have a problem with Nat2 and the inactivation of this medication. These people have been well reported on in the literature and it is clear that they get significant toxic effects from the first line therapy.

Recently this year there have been many publications on the molecular identification of resistance genes.

Several genes, including

katG, inhA, kasA and ahpC, have been associated with resistance to isoniazid. Recently rpoB and katG again.

More than 90% of rifampicin-resistant strains have been shown to possess point mutations in an 81-bp rifampicin resistance determining region of the rpoB gene. This is important because
recently, non-commercial molecular methods for rifampicin and isoniazid susceptibility analysis
have been

The problem is that this method is not widespread. Even worse, there exists geographically variability in resistance not related to genotype. However this has not stopped the patenting of resistance assays. I am certain their is a buck or two to be made off of the identification and proper treatment of this life threatening disease.

The Sherpa Says: XDR-TB is bad news, but soon we will have personalized microbial resistance tests to avoid dangerous and ineffective treatment. In addition we will have pharmacogenetic tests to prevent INH toxicity. Thus giving the right bug the right drug for the right host.

Wednesday, May 30, 2007

Hemochromatosis stories.

Lisa Lee posted about "House" last night. It made me laugh. I couldn't help but think how the media really portrays health care. It is down right scary. Most, like the media over-hype the non-dramatic and fail to catch the essence of medical culture. It is also scary how they miss the REAL issues. Did you know that in real life if you are "coded" you have less than a 15% chance of leaving the hospital? On TV it is over 75% And the way they portray disease......don't get me started :(

But what's even scarier is having to suffer through disease. I always like to check out the support blogs and this is one I feel strongly about. They express their difficulty with phlebotomy, the traditional treatment for Hemochromatosis.

Which brings me to my last comment. The American Gastroenterological Association recommends Iron Studies to evaluate for Hemochromatosis, not genetic studies. There are some shortcomings to this approach.....What if you are a pre-menopausal woman? Sure your iron will be lower than most with Hemochromatosis. But it will be elevated. The moral of the story, know your ethnicity, know the symptoms, and stay aware.

Lastly thank you to all that have visited The Sherpa's Shoppe. I am not looking to make any money, I just wanted a shirt that said "The Gene Sherpa" and didn't feel like buying 20.

Coumadin and Cancer!

There are two things I would like to post today. There have been a lot of posts regarding the new findings in FGFR2 and risk for breast cancer. I said yesterday that the population attributable risk was less than family history. This is correct if you are talking about pre-menopausal breast cancer.

I have taken some time to review the article with a fine tooth comb and here are my summary hot points.

  1. The study only analyzed post-menopausal, non first degree relative, "sporadic" breast cancer. Thus these findings may not apply to you if you have a first degree relative with breast cancer.
  2. The risk for having cancer is increased even if you are wildtype ("normal") for this FGFR2 gene. Therefore the O.R. of 1.64 should be compared with 1.20 for the wildtype Odds Ratio.
  3. The authors note that in a pre-menopausal population these findings were NOT associated with increased risk

Second Item. At the American College of Cardiology meeting in New Orleans an announcement was made that there is a 1-hour rapid genotype analysis for coumadin metabolism genes VKORC1 and CYP 2C9. Interestingly enough a physician Dr Jeffrey Anderson found that 72% of his patients on coumadin had a variation affecting metabolism of this blood thinner.

The Gene Sherpa Says: You must always use a guide to identify whether a test is useful or a study is useful. Unless you are already a Sherpa. This breast cancer finding in a subsegment does not represent all breast cancers! And We are well on the way to personalized medicine if we can genotype in less than an hour! Coumadin is a dangerous medication that can cause severe bleeding. I am certain that this point of care testing will find its way into the primary care physicians office. Now who's going to do the counseling??????

Tuesday, May 29, 2007

So Whaddya Think? Rick from My Biotech Life put together this little guy. He seems motivated, excited and ready to hit the trail. But I need to know....Should he stay or should he go? Oh and about this weekend's posts regarding "major breast cancer genes" The media seems to think they are the best thing since BRCAs.

The Sherpa Says: Hogwash. Those genes have so little penetrance that a family history will tell you more. And to Hsien and EyeOnDNA, if you don't have a family history, then an environmental history will indicate even more risk than these genes. One things for sure, I am glad I don't live in Canada. But as for the Diet Coke....I threw mine out yesterday :)

Sunday, May 27, 2007

The Genetic Counselor

Thanks to Bertalan over at Science Roll for pointing out a new blog/website called Genetics Counselor. This website has some interesting YouTube videos on it today. I tried to access the "blog" but was forbidden. I have to caution you all......Do not trust health care info unless the website is at least HONcode certified. I have no clue who writes for this site, their credentials, or their aims. That being said, the issues brought up in the video are REAL. I am most opposed to DTC because of these precise problems, including the lack of human contact while "phone" counseling. Another issue is the difference between counselors and geneticists.

The genetic counselor is different than the Geneticist is several ways.

  1. Geneticists have Medical Doctorate, Genetic counselors have an MS usually in a genetic field.
  2. Geneticists have taken pharmacology, microbiology, human anatomy, histology, pathology and several other medical school courses that counselors have not.
  3. Genetic counselors counsel patients but can order tests and give health care guidance ONLY under the care of a physician. (sometimes reasonably so, sometimes not)
  4. Counselors have a log book of 50 cases seen. To sit as a Geneticist you have 150 cases, 2 years of residency (at minimum) and 2 years of Genetics Fellowship (At minimum)
  5. Neither field is BETTER. We are just DIFFERENT from each other.

The Gene Sherpa Says: There are great counselors out there and there are also some bad ones please ask to also speak with the geneticist or physician if you feel uncomfortable with the counselor. Personally, I have the best Genomic Counselor in the world working with me. She is brilliant, talented and looking to move Personalized Medicine to the public.

Friday, May 25, 2007

The Funny Thing About Blogs

I just found my interview from Science Roll on the Reuters website today. Imagine my surprise when I am just googling myself and I come up with this! It goes to show as portrayed in this month's Harvard Business Review case study, Googling can get you into a heap of trouble, or raise your decide. I know this is a very Non-Personalized medicine post, but what it does illustrate is the power of collaboration in getting the word out about the future of health care. I will be offline for the weekend only because I am on call in the hospital Saturday and Monday :(

I hope everyone has a great weekend, and for those in the US....Happy Memorial Day!!!

Thursday, May 24, 2007

Blame Portugal

With all apologies to my good friend Rick Vidal at My Biotech Life I am here to report a tremendous disservice done to all of us western hemispherians(is that even a word?) by the Portuguese.

On the 20th of May in the Journal of Clinical Oncology an article was presented examining the BRCA2 rearrangements in 210 high risk cancer families. The rearrangement they described, occurs in 1/3 of all male breast cancers that they identified.

Why the big deal? Well, only 7 rearrangements to date have been described in the BRCA2 gene. In addition these rearrangements are not picked up in point mutation sequencing. Which brings me to a very important point regarding genetic testing. No Test Gives a Yes or No Answer. These tests require skilled interpretation as well as counseling to evaluate for further need of testing. This is the case with BRCA rearrangement analysis. This topic was covered by here. According to a study in JAMA back in 2006, several families testing NEGATIVE for BRCAs actually had rearrangements in these genes, leading to faulty function and cancers.

So here's where I say Blame Portugal. This founder mutation they identify is the most reported rearrangement for BRCA2. This is screwing up physicians who are only testing for BRCA point mutations. Such misleading results can give families a false sense of safety that they are not BRCA carriers.
"Portuguese people have been intensely migrating throughout the world since the XVth century first as trading sailors, and later as emigrant families, but most of the time crossing their genetic background with other people's. For this reason the researchers suggest that screening of this BRCA2 mutation "should be extended to all high-risk breast cancer families with Portuguese ancestry", in order to identify grater numbers of healthy women with a higher-than-average breast cancer risk, and offer them adequate preventive measures. "
The Gene Sherpa Says: I agree. Cancer in your family plus Portuguese ancestry equals BRCA rearrangement testing as well as indicated genetic screening. This is why it is so important to know your family history and ethnicity.

Wednesday, May 23, 2007

Personalized Medicine. Coming To A Hospital Near You!

The Houston Business Journal today reports on a ground breaking ceremony for Baylor College of Medicine.
"The soon-to-be Baylor Clinic and Hospital will be constructed at Old Spanish Trail and Cambridge Street in the Texas Medical Center area.

The campus will include an adult hospital, outpatient clinics, faculty offices and research space. The fully integrated health care facility, which will focus on personalized, gene-based medicine, will be open for business in 2010.
The Houston-based school also said its "Best Minds, Best Medicine" fundraising campaign is nearly half way to its $1 billion goal for clinical, research and education projects."
Baylor is best known in genetics circle as the place you send your CMA/CGHs. Personally, this is a great accomplishment. They now join the ranks of TGen, Mount Sinai, Duke, Mayo, Michigan State and Harvard in planning and implementing "Personalized Medicine Departments/Hospitals"
The problem I see is: Whom will talk with the primary care physicians in a language they can understand? Surely these patients will get genetic guided therapies and hopefully get some excellent counseling, but will the PMD have the knowledge to understand what was done? What about the patient. Will there be an educational program directed at clinic physicians? Where do non-clinic patients get their care? Will the summary reports be at a level the PMD can digest?
The Gene Sherpa Says: All this planning is great, but can we have something Right NOW?

Tuesday, May 22, 2007

The Problem with Avandia

Warning....This is a non-genetics post (for now)

Yesterday in the media and the New England Journal of Medicine an article was released. This meta-analysis implicated a PPAR gamma activator named Rosiglitazone in the increased risk of heart attack, and death from heart attack. The risk fo heart attack was increased by 43% and the risk for death from cardiovascular causes was increased by 64%. Now before you get too crazy let's do some data analysis.

  1. The study is a meta analysis of 42 articles. This methodology is fraught with problems.
  2. The second result....64% increased risk of death is not even statistically significant P value of 0.06 with a confidence interval which includes REDUCED RISK OF DEATH.
  3. This study is a policy play, based on the fears of Vioxx.

The Gene Sherpa Says: Don't get me wrong, if you have risk of heart disease in the family, then you should not take this drug now. At least until a full proper study can be done. But please, don't freak out. Just talk to your doctor about this risk!

Personalized Medicine and Prostate Cancer

I had said before how important replication studies are. It does bear some reminding though. replication lets us know that we are on the right track. There can be many false findings in the genome, especially when we are unsure what a certain marker does or does not do(confusing, I know). With that being said I report on a marker that has been linked to aggressive prostate cancer.

Prostate cancer is extremely common and tends to be more aggressive in certain populations. In fact, there are some doctors who opt not to treat the elderly because of the risks outweigh the benefits.

The marker which is being replicated was initially found by the deCode company back in 2006
Northwester reported on the findings at the American Urologic Association meeting this month.
What are they?

  1. This marker is twice as common in African Americans (more aggressive prostate cancer is often in AAs)
  2. If you carry the marker you are 40% more likely to have a family member with prostate cancer
  3. You are more likely to have metastases if you carry this marker

The Gene Sherpa Says: This study shows the heritability of prostate cancer, and more importantly aggressive prostate cancer. Perhaps by identifying those with the marker, then we can go after the tumor more aggressively as there are several ways to treat this Cancer based on "non-molecular" staging.

Monday, May 21, 2007

Disturbing Drugs

In the most disgusting display of capitalism this side of the I don't know where Wired Blog posts about PharmaTV. Four companies, Johnson & Johnson, Pfizer, Novartis and Procter & Gamble are behind this disgusting "educational" television channel. The article can be found in the Guardian. I am deeply disturbed by this precedent. At least you can tell the difference between an ad and a show. True, even these days product placement, fake blogs, etc. continue to blur the lines.
The Gene Sherpa Says: What's next? DTC Gene TV? Shame on all of you.

BRCA2 not just for adults!

St Jude has released some pretty amazing findings. Today is no different. The researchers there have implicated the BRCA2 (the gene, not the mutations) in the development of the brain. The study found that BRCA2 triggers the repair of damaged DNA from cellular replication in nerve cells. This effect was also found to suppress the development of Medulloblastomas. These tumors account for 1/5th of childhood brain tumors. When BRCA2 function is impaired (as is the case in breast and ovarian cancers) the mice studied developed medulloblastomas.

The Gene Sherpa Says: The jury's still out. It makes sense to me that this gene is involved in medulloblastoma. Especially because this gene is involved in Fanconi Anemia, which can present with brain abnormalities. However I caution the excitement...What prophylaxis is there for medulloblastoma? Brain-Ectomy(removal)?

Sunday, May 20, 2007

Weekend of Firsts

Today at ScienceRoll Bertalan Mesko gives me my first Blogterview. This follows hosting my first Gene Genie Carnival

I am very excited to have joined the ranks of those who he has

Personalized medicine is a passion for me. The true dream is to not have to call it personalized medicine or personalized genomics. The real name should be Medicine.

I put this cartoon here because it represents the "part-time" work I do for my blog, my training, and lastly my new medical practice. Let me tell you about what is so revolutionary at Helix Health of Connecticut (sorry, I am waiting to release the website).

  1. We follow you for life (Something clinical geneticists rarely do). This is necessary given the rapid changes in genomic discovery. Your risks change as we learn more.

  2. We are available for consultation anywhere you are (I can't share how). Just Call 1-914-954-6406. Soon we will have online booking :)

  3. We put Geneticists together with Internists, OB/Gyns, Genomic Counselors and Pediatricians (when needed) to make care plans one patient at a time. We go over them with the patient to make sure they understand the plan. More importantly, we frequently "check-in"

All of these things require web 2.0, and I am a huge supporter of technology in medicine.

The Gene Sherpa Says: This blog post says it all. Personalized Medicine is US.

Saturday, May 19, 2007

Gene Genie for 19 May 2007

In honor of my first Gene Genie

"It's a hundred times faster than the best serial supercomputer. It's a billion times more energy efficient. It's a trillion times denser than the best storage media. It's a teaspoonful of DNA that's a computer! And Leonard Adleman invented it."

Where is this supercomputer? Well, a group of Israeli scientists in 2004 published in Nature they had perfected the same thing where a DNA computer could detect cancer changes in cells and release a chemotherapy when positive.

Such is the same for our new "genomic revolution" Where will we be in 12 years?

This revolution is mentioned by The good folks at DNA Direct where they post twice on the subject The issue is clear, not enough trained specialist in genetics. But the question remains, is the 24th medical specialty really only restricted to metabolic diseases, developmental delay, and prenatal testing? I don't think so.......

Still we must never forget the roots of genetics. I am all too aware of the struggle people with metabolic diseases go through every day. We hear about this at Fight Pompe I am not surprised by the struggle to keep up with costs of this horrible disease.

Want to learn more about storage disease? Take a look at Sandwalk where we get 9 for the price of 1

Hsien Lei at Eye on DNA commented on the topic as well . She thinks we all can just get along. I say yes, patients and providers should get along. But patients and lab reps, just like pharmaceutical reps need to play nice too. Most of the time ;)

She also mentions the ugly side of testing at the Trinidadian Police Service where " lie detector tests would generate greater opposition than DNA testing" True, no lie :)

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........

Highlight Health reminds us that the beat moves on. The post quotes George Weinstock as saying 2007 is the year of Personalized Genomics. The full article can be found on the post. The Sherpa agrees. This year IS the year of the personal genome, from ARCHON to ILLUMINA we are moving there very quickly. I agree, that is why 2007 is the year I have launched the first personalized medicine clinic in the Greater New York City area.....soon to come out West.

Controlling our gene expression is important, and the sooner we figure out how to do it effectively we will start to see some "cures" for disease. Biosingularity points out a study working on the master PPAR, PPAR delta. We already have drugs for PPAR alpha and gamma. I used one just the other day to "cure" a woman's anti psychotic induced metabolic syndrome. Now that's effective use of your OWN DNA!

We too must remember we ARE what we eat. Our DNA is modified my our foods every day. The Agouti/Choline mouse study told us our food might also be affecting our offspring's' genes too. Scientific Blogging posts a study which is in concordance with that.

With all the debate surrounding the "utility" of web 2.0 pedias. Evolgen asks "Is scientific outreach good if facts are wrong" Something I question every day when I read the lay press regarding discovery.

These facts are often misunderstood and that's the problem. Even more likely, is what Rummy says. There are things "we know we know", things "we don't know we know", things we know we don't know" and lastly "things we don't know we don't know"

I can think of two big ones blown up over the last 2 years. The dual role of fibrillin in Marfan's disease, and Copy number variation. These two posts at Genomicron bring up that interesting content. The ideas are transmitted through road-kill.....uh I mean the opossum.

What's the solution to all this confusion? Well, at sites like Genetic Genealogists Ask the Geneticist we have some answers. More likely this type of site will bring up collaboration and communication.

That's why Rick Vidal has done a great thing by linking us together at the DNA Network

We will be able to debate, educate, and connect. That's what's amazing....

Let's flash back to 1995 and see what they say............

"By forcing the connection between computers and life, Adleman is making us rethink the meaning of both. Clearly, we have a lot of figuring left to do - but we also have new means for doing it."

Wired got it right. We do have a lot of figuring left to do and we do have a new means for doing it. Web 3.0, Medicine 2.0, and the people of the world.

Thanks for letting me host. The next Genie will be at Eye on Dna

Friday, May 18, 2007

Ex Myriad Backlash


Today I was called a genetic elitist. See Beware Doctors

Let me state equivocally. I am not a genetics elitist, I am simple man from the US who has seen his share of genetics tragedies. I would like to give you an example here.

A 45 year old man in my ICU dies after a Whipple. Why? He had let his weight loss go for several months. He hadn't seen a doctor for 3 years. He knew it could be his cancer, because the doctor told him FAP was cured by colectomy. Even better, he just had a one year old daughter. When I told the primary care physician there was PGD available, he said PG what?

I am not an elitist. I am trying to teach ALL comers genetics and personalized medicine. This guy who posted is clearly a disgruntled "ex-myriad" employee. I am sorry to have hurt his feelings so bad that he needed to call me an elitist. But I put it out here to serve as a warning.

These companies are coming and they are looking for your dollar under the guise of "genetic populism" Don't be fooled. If they were reasonable, then they would want to educate and empower physicians. They would help me design tools other than hand out cards which often get thrown in the trash. The education they choose to portray is not the NORM. "Your patient could have a 100% chance of developing hereditary cancer". That is alarmist!
The Gene Sherpa Says: Mr Wisconsin I am sorry, but you portray/assume too many people as genomic savvy. That is DANGEROUS! We have to keep our defenses up. I am here to guide you, to show you the risks of following the pack, testing without context, and acting on fear. The public needs to be wary of inappropriate testing. Especially until proper genomic non-discrimination law is passed
Lastly, I am hosting Gene Genie tomorrow. Stop by in the afternoon and see what I have in store for you :)

Thursday, May 17, 2007

Great Blog, Great Man

On occasion I like to make note of some person, event or thing that contributes to the future of health care and ultimately personalized medicine. One of these people is Bertalan Meskó.

He is a medical student at the University of Debrecen, Hungary (4th year of the 6). He has set up an amazing blog at Scienceroll whose aim is to make medicine, genetics more readable even for those who are not too interested in these.

If he were just to do that it would be a great thing. However, the soon to be Dr M is planning to help deliver the tools of Web 2.0 directly to physicians as he has to myself. He describes this synergy as Medicine 2.0. I currently am pointing all of my medical students and residents directly to his blog. I highly recommend it.

He has been interviewed several times and presents some great material.

I for one am extremely thankful to have a person willing to translate the technology of today allowing all of us to create the medicine of tomorrow.

Thanks Berci, I look forward to your exciting news.

Wednesday, May 16, 2007

This week in NEJM

This week Kathy Hudson Ph.D. opines on the difficulty of prohibiting genetic discrimination, detailing the hurdles that this legislation has had. If you have been asleep at the wheel, HR 493 passed the house 420-3.

This article also points out the huge loopholes in the Health Insurance Portability and Accountability Act, including its lack of addressing genetic information for underwriting purposes. Currently 35 states have some limited form of discrimination in employment, 47 with health insurance, leading to an inconsistent approach to prevention of discrimination. The states' legislation are swiss cheese like and difficult to apply. For example, some laws exclude genetic tests from "routine lab tests". Given that many genetic tests are "routine" these laws are now outdated and do not apply.

I would like to take a closer look at this proposed legislation now.

First what the legislation does:

  1. Prohibits group and individual insurers for using genetic info in setting premium or contribution amounts

  2. Prohibits insurers from requesting/requiring a patient undergo a genetic test

  3. Prohibits employers from using genetic information to make employment decisions

  4. Prohibits employers from requesting genetic information about an employee or their family

What it does not do:

  1. Does Not prohibit medical underwriting based on CURRENT health status

  2. Does Not mandate coverage for any genetic tests or treatments

  3. Does Not interfere with a physicians ability to request a patient or their family members undergo genetic testing

  4. Does Not create special remedies for employers other than those outlined in the Americans with Disabilities Act

  5. Does Not prohibit workplace collection of genetic information for genetic monitoring programs such as wellness programs, state and federal medical leave programs, and in cases of inadvertant acquisition of this information, But Does prevent the employer from disclosing or using this information.

The Gene Sherpa says: The bill has passed one Senate subcommittee and now sits poised to become law by the fall. I for one am very excited about the possibilities this legislation brings.

Direct To Physician Testing... Myriad re-enters the fray.

According to my insider sources it appears that Myriad is going to launch a Direct To Consumer testing campaign for Hereditary Breast and Ovarian Cancers. Their quote is:

  • "Because 1 out of 10 patients in your practice may be at risk for hereditary breast or ovarian cancer....Help Turn the Tide"

What happened the last time they campaigned? Demand for counseling went up 244% In addition there is a significant amount of literature that indicates the number one reason a "non-geneticist" orders a genetic test is patient request.

There are several ethical issues that need to be addressed with direct to consumer testing.

  • A number of these tests lack data on their accuracy and reliability, making interpretation of results difficult.
  • DTC genetic testing is undertaken outside the context of the physician-patient relationship and may lack appropriate individual and family genetic counseling,
  • This often is leaving the consumer vulnerable to potential harms, such as misinterpretation of results, including false positive or false reassurance, with limited or no benefits

There are several solutions to these problems. None of which should exclude a trained health professional. Remember what I said before "beware the doctor peddling genetic tests"

The Gene Sherpa says: New York in October, the Avon Breast walk, Myriad and its DTC brokers will make some serious cash. Please make sure it is not at YOUR expense. Get the right follow up, get the continuity of care, and BEWARE NON-GENETICISTS SELLING GENETIC TESTS!

Tuesday, May 15, 2007

Save a Life!

In a recent publication in Lancet it was found that those who received chest compression only CPR actually had better outcomes if performed in the first 12 hour. It appears there is a "golden window" of 12 minutes which perfusion is much more important than oxygenation. This has turned the CPR world on its head. I am posting this here, not because there is some genetic twist. I post it to hopefully save a life or two. There have been several publications linking fear of catching a transmissible disease and decreased desire to perform CPR. Here's the good news: Compressions work just as well if not better initially.

The Gene Sherpa says: Scared of mouth to mouth? Just give compressions and call 911.

Archon X-Prize Here We Come

This week in the Proceedings of the National Academy of Science an article entitled:
"Single-molecule mass spectrometry in solution using a solitary nanopore" was published.

Why is this mouthful of words important? Well, the future of genetic testing and sequencing is going to change and this is the likely direction. This pore, created by a bacteria (Staph Aureus) is only 1.5 nanometers. For appreciation, the human hair is 10,000 nanometers. What I think is ironic is that the enzyme used to create the pore actually gives staph its ability to really make us humans sick. The technique used is remarkable...I don't know if anyone has seen a tandem mass spec before. But it usually takes up the size of a lab table. This procedure could actually be accomplished on a microchip!!! This study is a proof of concept study done in Ohio and Brazil which demonstrates the fidelity of molecule size prediction. I am sure there will be more to follow.

In addition Harvard has gotten into the game of nanopore sequencing and will likely be the world leader. But this is no surpirse. They have been in this nanopore game since the early 2000s (did I just say that?) The rough estimate for launch in this project has just gone from 7 years to 3.
The biggest problem clinicians have with genetic testing is it often takes too long with some of the quickest results taking longer than 6 hours. Nanopore sequencing could give answers in less than 2 hours. This would allow a physician to dose medicines, change treatments, identify disease in a much more reasonable window of time.
Do I see nanopore sequencing being used in the ED? Not quite yet, but the pharmacogenomic implications for personalized medicine are huge!!!!
Thanks Jason for putting this on the Radar Screen back in March.

Sunday, May 13, 2007

Google Innovation? Google Conspiracy? You Decide

In reading through my RSS feeder I stumbled across an interesting video at Testing Hiatus. It comes from the website Master Plan the Movie. Before you watch this YouTube video I first would like you to take a gander at an excerpt from

"The Google Story"

Sergey Brin and Larry Page have ambitious long-term plans for Google's expansion into the fields of biology and genetics through the fusion of science, medicine, and technology. . . .One of the most exciting Google projects involves biological and genetic research that could foster important medical and scientific breakthroughs. Through this effort, Google may help accelerate the era of personalized medicine, in which understanding an individual's precise genetic makeup can contribute to the ability of physicians and counselors to tailor health care treatment, rather than dispensing medications or recommending treatments based on statistics or averages.

"We need to use the largest computers in the world," Venter said. "Larry and Sergey have been excited about our work and about giving us access to their computers and their algorithm guys and scientists to improve the process of analyzing data. It shows the broadness of their thinking. Genetic information is going to be the leading edge of information that is going to change the world. Working with Google, we are trying to generate a gene catalogue to characterize all the genes on the planet and understand their evolutionary development. Geneticists have wanted to do this for generations."Over time, Venter said, Google will build up a genetic database, analyze it, and find meaningful correlations for individuals and populations. . . . Google's data-mining techniques appear well-suited to the formidable challenges posed by analyzing the genetic sequence.

It has begun work on this project, but has not been required to disclose any information about it publicly since the work has no impact on its current revenue and profits."People will be able to log on to a Google site using search capacities and have the ability to understand things about themselves as they change in real time," Venter said. "What does it mean to have this variation in genes? What else is known? And instead of having a few elitist scientists doing this and dictating to the world what it means, with Google it would be creating several million scientists.

"Google has empowered individuals to do searches and get information and have things in seconds at their fingertips," he went on. "Where is that more important than understanding our own biology and its connection to disease and behavior? With Google, you will be able to get an understanding of your own genes. Google has the capacity to do all of this, and it is one of the discussions I have had with Larry and Sergey."
Ok, So now you can watch the movie at Testing Hiatus

Let me know what you think. Does Don't be Evil mean Be Good? Or Does it mean something else?

Saturday, May 12, 2007

Vote for Me

What a network we have! Our group at The DNA Network has several bloggers nominated for awards. The groups are

  • Best Educational Blog where Hsien Lei at Eye on DNA, myself are up.
  • Best Health Blog where Hsien Lei, Myself, Berci at ScienceRoll are in the hunt. BTW Science Roll is doing great with over 200 votes so far!
  • Best Blog Design Eye On DNA. Very sharp Hsien.
  • Best Blog About Stuff.....what stuff? Personalized Medicine right here.

So get out there and vote. I know we may not look as good as Sanjaya, but we need your vote just as bad :)

Also get out there and nominate. I am going to nominate some more blogs in this awesome DNA Network, because they rock!


Chemotherapy Toxicity Genes

Imagine if you could predict who would get the nasty side effects of chemotherapy before giving it. We could then taper the chemotherapy giving less of a dose and achieve the same response. Well, the first part of that dream is here today. At St Jude Children's Research Hospital they have been actively investigating pharmacogenomics and chemotherapy. In a study to be released in the May 15th edition of Blood we have just that.

The major findings include

  • During the induction phase Vitamin D Receptor polymorphisms were linked with gastrointesinal symptoms (diarrhea, nausea, vomiting) 6.85 times more likely.
  • Polymorphisms in Cytochrome p450-Family 3-subfamily A-number 5, were almost 5 times more likely to have infections and Neurotoxicity
  • During consolidation phase the Reduce Folate Carrier polymorphism led to the GI side effects with a 10.4 odds ratio.
  • UGT1a1 polymorphisms led to jaundice as well as reduced clearance of an agent called methotrexate (a chemo drug) perhaps leading to increased toxicity as well

This is a major study, that has had some replication in one gene or another. But the compiling of these polymorphisms has not been done. Likely we will need one more round of evaluation. But after that...we could have a pharmacogenomic test for side effects.

The Gene Sherpa says: This is great, but how do we adjust the chemo to avoid these reactions. We will likely need an adjustment scale based on polymorphisms. AKA Personalized Medicine! I am certain St Jude's has this in the works. Let's keep our eyes peeled :)

Friday, May 11, 2007

The Genomic Revolution AKA the birth of Personalized Medicine

An intriguing second post at the "official blog" for direct to consumer testing company DNA Direct brings some excellent points up.

These are points that I often use when trying to tell physicians what will happen if they don't learn genetics.

It often scares the hell outta 'em, or they say "nah no way, medicine is too complicated for the public to practice." Then they go back to practicing medicine the same way we have for the last century, microscopes, gram stains, and paper charts.

The problem has been festering away and the geneticists, internists and specialists have been asleep at the switch. A Summit was held on the subject Bruce Korf, president-elect of the American College of Medical Genetics realizes this. In fact he has been preaching about it for the last 6 years. You can read about it here, here and here.

Some questions

  • Who prescribes your blood pressure meds? Your Internists/Family Practitioner

  • Who refers you to specialists? Your Internists/Family Practitioner

  • Who encourages you to quit smoking? Your Internists/Family Practitioner

  • Who argues with insurance to get paid? Your Internists/Family Practitioner

  • Who doesn't have the time to see you let alone continue their medical education? Your Internists/Family Practitioner

I am collaborating with Dr Korf as well as leaders in Genetics and Internal Medicine at Yale, Mount Sinai and Harvard to develop a curriculum for residents. The problems

  1. Getting the residents to attend conferences on topics the perceive are of no use to them. (why is this? The reason: their instructors can't speak genetics let alone teach it)

  2. Finding physicians who speak genetics and can teach genetics. (There are 83 Geneticists who have certification in Internal Medicine)

  3. Getting Residents to understand Genetics (Most don't know introns aren't junk)

The solutions? Are tough. I think we need to teach the teachers, we also need to teach the medical students. Physicians have not changed our level of genetics understanding in the last 30 years. That's why they all think Huntington's is the prototypical genetic disease. When I tell them that MI is the new prototypical genetic disease they laugh. How can we fix these attitudes?

Even psychiatrists agree that genetics is important but they realize the lack of knowledge they have.

Whether it is your OB/Gyn missing indications for referrals 9 out of 10 times or 1 in 3 Internists who misinterprets a genetic test for APC. My oncology friends still don't understand mitochondrial inheritance.

Could the lay person do better? Maybe...But could they write a prescription for the Cox-2 Inhibitor they now should be taking? Who will send them to the surgeon? Who will admit you to the hospital? Who will read and review all the articles needed for your care? Who will?

The solution lies in your hands. The solution is to encourage your doctor to learn genetics. Ask him about DNA and your health, ask her about your drugs and your genes. Force the issue, read as much as you can. When your doctor refuses, leave her care. Find a doctor who will learn. But please, please, please don't leave it up to yourself.

The Gene Sherpa says: The solution is up to you. It is up to your doctor. It is up to all of us, together learning and teaching each other. To get the best health care possible. Delivered by a licensed health professional, not by Domino's..........Wake up people or Wal-Mart is where you will get your genomic revolution!!!

African Americans, Family History and Lung Cancer

A pre-publication release of the Journal Chest includes a study assessing family history of lung cancer and likelihood of acquiring a tobacco related malignancy.
From the study:

"In 2006.....estimated that 174,470 new lung cancer diagnoses and 162,460 deaths from lung cancer will occur. Lung cancer remains the leading cause of cancer related death, regardless of gender."

I just saw 2 new cases yesterday myself :(

"Among case relatives, African Americans were 2.44 fold more likely to have head and neck cancers and 1.86 fold more likely to have any tobacco-related cancer compared to white case relatives"

This is where we have to wonder what role detoxifying genes such as GST polymorphisms. It has been show that they do play a role in risk of disease. If only DNA was collected from the participants in this study..........

Most scary for African Americans with a first degree relative diagnosed with Lung Cancer in this study

  1. They are 13 times more likely to have head and neck cancer

  2. Almost 4 fold more likely to have any tobacco related cancer

  3. 4 times more likely to have any tobacco related cancer other than lung

For the Caucasian analysis it appears that African Americans are at 2 fold increased risk compared to their White counterparts when it comes to Lung Cancer.

The Gene Sherpa Says:

We all know smoking causes cancer. But those who continue to play Russian roulette with Marlboros would like to know how hard they should try to quit. This study was limited by only studying early onset lung cancers (less than 60) Kick the Habit Now!

Thursday, May 10, 2007

Too Far

So I have been reading another blog linked in my brand new DNA Network a Feedburner network set up by Rick at My Biotech Life. I was invited by the group and I am very excited about participating in the discussion. To have such a network encourages debate and solutions. I love the ability to communicate with other persons about the future of health care. That being said, I think this blog may have gone too far. They are talking about Direct to Consumer Testing

  • "Not surprisingly, the genomic revolution has a lot of medical professionals who aren't geneticists* concerned about who's doing what, and how."

Not only Non-geneticists, but GIANTS in the field of genetics (Francis Collins, Margretta Seashore, Kurt Hirschhorn, Ed McCabe, Victor McKusick to name a few) have some serious concerns about how things are going. Including Gene Patents, Enzyme Replacement costs, and yes Direct-To-Consumer Testing. This blog goes on to say.....

  • "It shouldn't be a territorial issue, but when money is involved, it inevitably raises this issue."

I would venture to say that these physicians and scientists are less concerned about money than they are the stewardship of their respective fields. Shame on this author for insinuating that they think like her. I know these people and money is the least of their worries. Lastly she finishes with

  • What's the difference between a direct-to-consumer company that provides medical services and a for-profit physician group that provides medical services?

The answers are many let me start with the obvious ones first.

  1. Medical practices do not get paid for the tests they order for patients. It is ILLEGAL by Stark II laws. Nor do they get paid for the interpretation of these tests.
  2. The DTC company does not examine you, they may not even do a family history.
  3. The physician group has a referral network to send you to when something is diagnosed.
  4. The ideal group will continue to follow you even after the testing.

I could go on but I think you get the picture. Shame on this blog (which is part of my network) for foolishly trying to think they are even in the same category as a group of physicians who have ethical and legal obligations that DTC companies are not even close to being subjected to. Perhaps the physicians who are under their employ are subjected to these regulations, but do they even carry out medical care?

Must we have this argument? Collaboration is what is needed not the "framing of MDs as money hungry" I would say that perhaps there is some self-projection going on with this DTC company.

What do you think?

Of Media and Men...Down Syndrome Evangelists

Yesterday in the New York Times there was a front page story about first trimester screening for chromosomal diseases and the families of children with Down Syndrome. These families are inviting pregnant women who test positive to come meet their children with Down Syndrome. They do this in hopes of showing the pregnant woman what it is like to have a child with Down Syndrome.

I normally don't get too heated about the media. There are things I generally accept regarding the old media and genetics

  1. They have people reviewing the science who have little if any genetic qualifications

  2. They hype everything

  3. They always look for a protagonist antagonist situation

  4. They never look to support personal choice (Trust me they already have chosen for you)

So with that in mind I invite you to read this article if you haven't already. I would like to give you a little snippet here:

"The parent evangelists are driven by a deep-seated fear for their children’s well-being in a world where there are fewer people like them. But as prenatal tests become available for a range of other perceived genetic imperfections, they may also be heralding a broader cultural skirmish over where to draw the line between preventing disability and accepting human diversity."

Come on now NYT, word choice is everything here and it is clear that this paper feels strongly NOT in favor of these parents.

"They are pressing obstetricians to send them couples who have been given a prenatal diagnosis and inviting prospective parents into their homes to meet their children."

I have a hard time pressing obstetricians to refer for genetic counseling. I have a hard time believing that these parents are even given the time of day by the Ob/Gyn, let alone being influenced or bullied.

The Gene Sherpa says: In the spirit of non-directive genetic counseling (something I rarely see CGCs do completely and something I wonder if the public even wants) we should offer all options to the patient. This public forum/support group could be mentioned just as easy as a D&E. In fact I think all options should be on the table PRIOR to testing.

Read the article and let me know how you feel.