Friday, September 26, 2008
Posted by Steve Murphy MD at 12:04 PM
I have received great response to our HelixGene Foundation. We are quickly building our community. It is so heartening to see everyone support this effort. It is frankly, breath taking!
Today I will be headed to a wonderful company. They are called Cine-Med. They are joining forces with the Sherpa to create Genomic CMEs. We have some great ones that are fast approaching launch.
My mentor told me that I am doing to much. But I have to tell you, I am not doing enough. I need your help. Help empower physicians to learn and practice Genomic Medicine!
Remember what I said about NCHPEG.....only 6 of 100 primary care physicians had ever heard of them. Instead they would rely on the Sunday NY Times. There has to be a better way! Either we launch a multi-million dollar awareness campaign for NCHPEG or we partner with someone who already has that recognition. I am working on that one too!
The Sherpa Says:
The NYT article on Sergey was the call to action! We need to act by uniting and guiding this field up the mountain!
Wednesday, September 24, 2008
Yes finally, at last I am going to release my Sherpa Plan!
Thank you to all who have helped form this unique set of operating instructions to help rescue the promise of personalized medicine.
Now to Problem Number One....
Lack of Public and Physician Education by qualified sources.
How many people have heard of NCHPEG? I have, they are the National Coalition for Healthcare Professional Education in Genetics and they are a fantastic resource. But.
Well, my team took a poll (non-scientific) of 100 primary care physicians........how many do you think have heard of this organization............6 and they all had spoken with a geneticist in the last 2 months. In other surveys, physicians state that they rely on the same media that patients do to receive information about genetics. That's just not right!
Friends......we have a big problem when the people who are supposed to be implementing genetics get their information from an unreliable news media. Why are they unreliable? They like everyone else are expected to do more with less.....thus fact checking has become a thing of the past........
So therefore, if physicians are going to use the Sunday Times as their information, then we are going to fact check it ourselves......
Together with Drew Y, we are creating a community to fact check genetics reporting. It is called HelixGene Foundation......Thursday we will have sent an email to over 1000 genetics professionals inviting them to join our community.....
Attention Media and Public Relations! You are now forewarned.....We will keep grades on all of you and post them so that the public and physicians who are reading your articles are given the courtesy of Peer Review!
Want to join our community? You need to verify your PhD, MD, or CGC credentials and then we will sign you up.
The Sherpa Says: If we can control the accuracy of information, we will avoid overselling genomics. Why is this important? To prevent articles, like the one of Dr Khoury in the NEJM essentially bashing SNP scans. The problem? PMDs viewed that article as marginalizing the whole field of personalized medicine. Not just the SNP scan! Trust me Dr Khoury, we need more than a treadmill to carry out personalized medicine.
Friday, September 19, 2008
What I find interesting is how a SNP finding and a blogger can set the press a fire.....especially when the blogger is a junior member of the billionaire's club.
In this case I am speaking of course about Sergey Brin who recently published a blog post on his risk for Parkinson Disease. It helps understand why his wife launched 23andWe......
This research would have great potential if the Company 23andMe would obey the "rules and ethics" of common human research by allowing patients to remove their samples from 23andMe's database if tehy so chose.....and more importantly, consenting a patient when the sample (which 23andMe would now own) would be tested for other things...
23andMe's mission is to be the world's trusted source of personal genetic information
They have a long way to go........
That being said....I think we should talk about LRRK2 and what it means for Sergey and others who carry it. From Sergey
It is clear that I have a markedly higher chance of developing Parkinson's in my lifetime than the average person. In fact, it is somewhere between 20 percent to 80 percent, depending on the study and how you measure," Brin said.
That is 20 percent to 80 percent higher than the average risk......Not 80 percent likelihood to develop Parkinson Disease. That 80% risk is the case for BRCA carriers in breast cancer, but not this LRRK2! This was a statement on his post which some people may get confused by...so don't.
Mr. Brin, who made the announcement on a blog, says he does not have the disease and that the exact implications of the discovery are not clear. Studies show that his likelihood of contracting Parkinson’s disease in his lifetime may be 20 percent to 80 percent, Mr. Brin said.
Parkinson Disease affects approximately 1% of the population by age 65% and 4 to 5% by age 85 years. Therefore the lifetime risk is 2-5%. So a 1.2 to 2.1 Odds ratio would be 4% to 10% roughly. Not 80%!
There are several genes that have been linked to PD, including alpha synuclein, PARKN, PINK1, DJ1 which have all been linked to familial PD. LRRK2 is a realtive newcomer to the field with good publications starting in 2005. For reference the first BRCA publications were in 1994. It took us 10 years to really be able to fully understand and explain what the risks are. We still have problems with this though.
There are several misconceptions about BRCA as there are for LRRK2....worse yet, counseling for LRRK2 can be confusing. Which is why perhaps
Because there are only a small number of genes which are known to have a very substantial effect on health (e.g. 10 times the average risk)
I felt the possibility of discovering something very important to my health was just a hypothetical exercise. So, when my wife asked me to look up G2019S in my raw data (23andMe scientists had had the forethought to include it on their chip), I viewed it mostly as entertainment.....
LRRK2 is not one those genes that increases your risk by tenfold...
LRRK2 mutation accounts for 5 to 6% of familial PD and 1-2% of sporadic PD. Not exactly what I would call useful for a screening test. Mind you this is given for North Americans and Europeans.
These numbers however do change for a few ethnicities including North African Arabs, Ashkenzi Jews where it goes up to 29-37% of familial cases and 7-14% in sporadic....some studies say as high as 41% in sporadics, but the high sporadic data is not replicated.
What is familial PD? Well, at least one first degree relative must carry a diagnosis of PD.
I am not certain of Sergey's Ancestry.....perhaps he is African Arab or Ashkenazi Jewish? That might put his likelihood of having a mutation in LRRK2 higher.....
Interestingly in the largest study of Ashkenaim with PD to date the odds ratio to develop PD was 5.77 which is very high and fairly significant. Unfortunately, these data ONLY apply to Ashkenazi Jews from Israel as this was the population studied.
So don't go thinking it is that high for everyone. In this study, the Odds Ratio for developing PD in Ashkenazi patients with the LRRK2 G2019S mutation was 5.7 (CI 2.8 to 11.7). It is increases when you match age and sex to 8.6. Which has us thinking perhaps this is a sex effect? Not that sex, you perv!
What is the percent of unaffected carriers in the general population of Ashkenazi? 2.2%
That is a scary stat for my Jewish friends. That means this mutation is not nearly as common in the unaffected Ashkenazi Jewish population. This should be only interpreted for this Ethnicity! Not for Europeans or for Americans who do not have Ashkenazi ancestry!!
It was crazy that none of the other mutations in LRRK2 were detected in this Ashkenazi cohort. That certainly speaks for a founder effect!! Similar to the founder mutations in BRCA1/2
In dissecting out thet data a little more we see that the G2019S was found more commonly in Women and in Familial Cases for the Ashkenazi population.
So, I hope that helps. These data and perhaps the numbers Sergey quoted were likely those for Ashkenazi Jews. So if you are Tom Smith from Nebraska, chances are that the LRRK2 data you now could afford to get are not so dire. And even if you are Jewish, the penetrance of this mutation is 24 to 85%
Sergey's post was great and highlights a special issue. Ethnicity and its role in disease. We cannot apply one ethnic groups data to another. A study done on the Chinese does not apply to Northern Europeans. This is why SNP data can mislead and scare.
Here's the big question, when you found out you might get Parkinson Disease Sergey, were you alone? Would have liked to have someone there? Would you have liked to talk with a geneticist? Or was it like Joanna Mountain said to a friend of mine "Aww, Come on, this testing is just for fun"
The Sherpa Says:
At Helix Health of Connecticut, patients are seen that have family history of Parkinson Disease. I believe that all asymptomatic testing of this nature can be confusing and requires appropriately trained consultation....plain and simple. What if Sergey didn't have billions to through at this disease in hopes of a cure and to give him hope? He might be hopeless. In that case he might have even contemplated suicide......in the privacy of his own CPU......
Wednesday, September 17, 2008
The offshore location also differentiates Google’s plans from those announced by IDS, which plans to build up to 50 data centers on de-commissioned cargo ships moored at piers in major cities.
Posted by Steve Murphy MD at 5:53 AM
Tuesday, September 16, 2008
I don't think so.....If that is true, I know a few comapnies out West that could have a problem.....
Turns out the publicist for my friend's friend must have gotten him a sweet article in the New York Times.
It turns out David Goldstein has been a contrarian forever. It turns out he is getting ready to publish a wonderful book. From the article
"This idea, called the common disease/common variant hypothesis, drove major developments in biology over the last five years. Washington financed the HapMap, a catalog of common genetic variation in the human population. Companies like Affymetrix and Illumina developed powerful gene chips for scanning the human genome. Medical statisticians designed the genomewide association study, a robust methodology for discovering true disease genes and sidestepping the many false positives that have plagued the field."
Well, David argues.....this idea is dead.....
“There is absolutely no question,” he said, “that for the whole hope of personalized medicine, the news has been just about as bleak as it could be.”
Wha????? David....is the common disease common variant theory equal to personalized medicine????
I would say no. What about Pharmacogenomics? I mean, come on...that's what you are studying. What about family history ascertainment? That's what you are publishing. Obviously in your mind, Personalized Medicine is not dead.
But the Common Disease Common Variant issue that is a much more interesting question.
Let's just say it is dead....as my Chairman Rick Lifton might also be in agreement with.........What happens? SNP scan testing companies go away.......Affy, Illumina, etc see a drastic cut in their machine usage and purchases (Yikes) and all the hard work we put in for the HapMap gets thrown away.....
No one is going to let that happen. So let's just say it is not dead but on the Injured reserve. If that is the case how do we rehab it.....I have some ideas
1. We need to have better methods of phenotyping and analysis. Common disease is rarely the same in everyone and is likely to have multiple etiologies
2. We need to remember that rare variants interact with common variants and look at this from a systems basis.......I.E. "Both kinds of music Country AND Western" Studies need to be designed this way
3. Lastly, we need to look at the environmental interaction with these common variants. Diet logs, career information, exposures, etc...need to be incorporated into these studies.....
Iff, we do these things and still come up with nothing, then and only then will Common Variant Hypothesis be dead!!! But with the types of ideas on the other side I don't think they get that...From Dr. Goldstein,
Just as selection turns out to have pruned away most disease-causing variants, it has also maximized human cognitive capacities because these are so critical to survival. “My best guess is that human intelligence was always a helpful thing in most places and times and we have all been under strong selection to be as bright as we can be,” he said.
This is more than just a guess, however. As part of a project on schizophrenia, Dr. Goldstein has done a genomewide association study on 2,000 volunteers of all races who were put through cognitive tests. “We have looked at the effect of common variation on cognition, and there is nothing,” Dr. Goldstein said, meaning that he can find no common genetic variants that affect intelligence. His view is that intelligence was developed early in human evolutionary history and was then standardized.
Seriously? Do you really think Hawkins type of intelligence was the same as Picasso's? What about Mozart's? Einstein's.....The statement that intelligence is standardized is crazy....There is no way a bunch of man made cognitive tests can fully stratify the phenotypes of intelligence......It sounds impressive to the lay reader. But to me....it reeks......
The Sherpa Says: While Dr Goldstein is a smart and learned individual, he will not kill of the Common Variant Hypothesis.
Posted by Steve Murphy MD at 9:54 AM
Monday, September 15, 2008
An old post.......interesting that I seemed to be right on track....In reading through my RSS feeder over a year ago now I stumbled across an interesting video at Testing Hiatus. It comes from the website Master Plan the Movie. This is especially timely given the new shiny 399 USD SNP scan.....which BTW is still more expensive than Coriell's Free Scan!
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?
The Sherpa Says: 23andME has been in the works long before it hit the radar. See Russ Altman earn his advisorship to 23 and Me here. Lastly, there will be only one purchaser of 23andMe's data.....Google....end of story.
Sunday, September 14, 2008
The New York Times article was lovely.....
So was the New York State Department of Health....
the State Department of Health sent letters informing the companies that it is illegal to offer medical tests in New York without proper licensing. Claudia Hutton, a spokeswoman for the Health Department, said that 23andMe also received such a letter, along with three dozen other DNA-testing companies.
A spokeswoman for 23andMe, Rachel Cohen, said the matter was being negotiated with the state. “We are still talking to them and hammering out the best method to do it to take into account their interest in regulating the industry,” Ms. Cohen said.
Ms. Hutton said that if 23andMe has continued offering tests since receiving their warning letter in December, the company could be fined $2,000 for each test done on a New York resident. There was no sign of a Department of Health inspector at the party.
My father always said......if you have nothing nice to say.......well. I never really listened that closely to my father's advice....
The Sherpa Says:
Anne, you looked beautiful......
Posted by Steve Murphy MD at 10:55 AM
Saturday, September 13, 2008
So I was on the phone with my good friend Deb Heine. She told me that a great tragedy is occurring.....What is that? Well while everyone was out playing patty cake and hyping 23andMe's democratization of SNP scans, Athena was doing something more dastardly.....Who is Athena? In the late Classical Greek myths, Athena is most commonly described as the daughter of Zeus, born from his head after he swallowed her pregnant mother.
You may be asking who in the heck is Deb Heine? Well she is the founder of the Claire Altman Heine Foundation. Her daughter Claire was born with a horrible disease called Spinal Muscular Atrophy. What's crazy is that the carrier rate of this genetic condition is similar to Cystic Fibrosis. You may be asking yourself...."Doesn't every pregnant woman get offered carrier testing for CF?" The answer is yes.....even women who are not of northern European ancestry have been offered CF screening. Why? CF happens in other populations to, just not as frequently.....
Well, in the case of Spinal Muscular Atrophy(SMA), it IS a pan-ethnic disease! Not just for white people. It is a rate of 1:40 people. That's pretty high...
So what is the big deal? Well, in October the American College of Medical Genetics will be making it policy that every pregnant women be offered carrier screening for SMA.
Whoa! How many women is that in the US? 4,315,000 births in 2007 according to the CDC....that potentially means 4 million plus laboratory tests for SMA....which works in the case of Cystic Fibrosis where there are 65 laboratories that do those 4 million samples each year.......
Flash back to Athena, the goddess of war and also the Greek goddess of wisdom, war, the arts, industry, justice and skill. And it's laboratory counterpart who is none of these....
You see, Athena has the patents for SMA testing....and it is now shutting down laboratories all over the country doing this testing. Leaving only 1 laboratory to handle those 4 million samples.....That lab? Genzyme!
This is why patents suck......no matter how good Genzyme is...and trust me they are very god at this biz.........There will be a bottleneck, delays and there will be price gouging, that will costs insurers millions of dollars.
So while 23andMe was hailing the democratization of a minimally clinically useful test, Athena was "Dictatorizing" carrier screening and a much more clinically useful test.
The Sherpa Says: This is the problem with healthcare, all the buzz is on a company backed by google rather than on where the real story is. Why hasn't genetics gotten the time it deserves? It's time has come. I just wish the press would pick up on this too. Stop the gene patents, save healthcare....it is just that simple....patent processes if you want...but make it illegal to patent genes. If we fail on this aspect, we will fail the future of our citizenry.
Posted by Steve Murphy MD at 1:27 AM
Thursday, September 11, 2008
Tuesday, September 9, 2008
Posted by Steve Murphy MD at 6:07 AM
Monday, September 8, 2008
First I would like to apologize for the lack of postings on interesting topics lately. I am glad that others have picked up my slack. Notably Hsien and Bertalan's interesting posts this week. Or for an in depth post on the politics of health care and the reform movement check out VentureBeat
What I want to pay attention to today is the question I inevitably get asked when I speak to other physicians. "Is what you say feasible in a 7 minute consult world?" The answer is inevitably NO. I do not feel in my heart of hearts that we will ever be able to practice personalized medicine in a 7 minute consult world.
What's needed is a Revolution. We need a place where the patient has access to their records and their physicians 24/7. We need a place where the patient is given the skills to understand and manage their disease. My friend's 12 year old son can quite effectively manage his diabetes, how come a 45 year old venture capitalist cannot? Support is the key and learning is the motion required to open the lock. How do we make these things easier? How can we get doctors to teach their patients? What ever happened to true continuity of care? These are big questions that need answers. I don't have them all. But I am working with some great people who will find those answers.....
So the next question is "How can we have the knowledge to practice these things?" I often tell physicians to go back to college or read a book on genetics. If you don't have the time to do that, then you will fail your patients. This often meets an uproar of disbelief......I am pretty good at pissing people off. Just ask Lisa Lee at DNADirect ;)
In all honesty, we need some clinics who offer personalized medicine consultations. These specialists need to guide care in collaboration with PMDs. I am proving this model in NYC! Give us a call and we can arrange to start the relationship.
But there has been someone doing this since 1986!!!! Wha??? The HGP was only 3 years in and they were providing these services. Yes that is correct. Greats such as David Rimoin and Maren Scheuner helped form and develop this practice. It goes by the "trademarked" name GenRISK Adult Genetics Program. It has been in practice since 1986 offering several tests that you can see on their site. I have been critical of predisposition tests unless clinically indicated. This is an example of how a personalized medicine practice can be run.
The Sherpa Says: Genomic and Personalized Medicine need to be given in a continuity of care. Family history changes, medical history changes. A one time consultation cannot deliver that kind of service. Oh and what about pharmacogenomics?
Posted by Steve Murphy MD at 7:16 AM
Friday, September 5, 2008
Let's Join together and beat cancer down! As I posted earlier about Christina Applegate and now about Mia Perovetz. Cancer can destroy families. Why not stand up to it. That's what celebrities are doing tonight. My friend Walter recently posted on this.....you can see it Here!
We have to beat cancer! Tune in tonight September 5th, at 8:00 pm EST and PST, ABC, CBS and NBC will donate one hour of simultaneous commercial-free prime time for a national fundraising event. Tune in donate and let's stop cancer in its tracks!
Wednesday, September 3, 2008
Whether you agree with the plan or not this is an impressive argument made by T.Boone Pickens
http://www.pickensplan.com/. It's also a very impressive community he's building...
When you think about it the personalized medicine industry has some of the same challenges and some distinct differences...
Problem #1: US Healthcare costs (source: National Coalition on Healthcare)
In 2007, health care spending in the United States reached $2.3 trillion, and was projected to reach $3 trillion in 2011.1 Health care spending is projected to reach $4.2 trillion by 2016.1
Health care spending is 4.3 times the amount spent on national defense.
In 2005, the United States spent 16 percent of its gross domestic product (GDP) on health care. It is projected that the percentage will reach 20 percent by 2016.
Although nearly 47 million Americans are uninsured, the United States spends more on health care than other industrialized nations, and those countries provide health insurance to all their citizens.
Health care spending accounted for 10.9 percent of the GDP in Switzerland, 10.7 percent in Germany, 9.7 percent in Canada and 9.5 percent in France, according to the Organization for Economic Cooperation and Development.
Problem #2: Higher and higher bar set for FDA approval of new therapeutics in the same therapeutic class to treat the same disease with a "one size fits all" small pharmaceutical development strategy. Pharma has to spend more and more to face higher and higher hurdles to approval and their looking under every rock, inventing and naming new conditions and diseases and their pipelines are drying up. Trial and error medicine is dead.
Problem #3: As new companies address pharma's problems (Myriad, Genzyme, Vanda, Clinical Data, Algynomics, perlegen, genomic health, etc) by developing companion diagnostic tests to target therapy to individual patients ("likely responders") there are too few doctors (<500)>300M people.
Problem #4: Education. The lay-physician or GP has no formal training in genetics and has not likely seen genetic consults to discuss genetic testing. the physician has 7 mins to explain very complex subject matter with the patient putting undo pressure on the currently stressed system.
Problem #5: Distribution of tests. There are currently hundreds of small companies developing sophisticated molecular diagnostics which would adequately segment the "trial and error" population into a targeted and appropriate population for a specific therapeutic. But they do not have a central distribution channel for their personalized medicine tests.
My friends and I have a plan.....in two weeks we will begin to share it.....and we can all climb the mountain together.
HT: Matt Tindall
Posted by Steve Murphy MD at 6:26 PM