Family History, State of the Science

The NIH/CDC is hosting a conference next week. I conference I wish I could go to, but alas, I will be DOING family histories on my patients that week.

The conference will be held at the NIH in Bethesda. This is an NIH state of the science conference about Family History and its usefulness.

I for one, am very glad that the government is trying to address this super important issue. It is beyond due for an evaluation.

Why?

With the cost of a genome going to drop to 5000 USD by the late fall (trust me), we will soon see another level of DTC and Clinical lab set offering the genome as a predictive tool.

There are several reasons that Family History beats a Genome (For Now)
1. Phenotypic data of family history represents complex interplay of genes and environment

There is no way that a simple genome will be able to give us the story of how a human will develop. That is predicted by environment and genes, which are successfully covered by..... A family history.

2. 5000 USD is still more than what it costs to obtain a family history.

By the time the software tools are released, we will see that social networking and the internet will transform the costs of family history next to nothing. Which is still a long way to go for the genome scans.

3. We have no clue what most of the genome data means.

Indels or CNVs or SNPs, we have no freaking clue what most mean, we do know what a heart attack at 40 means.......

4. Even if we had everyone's genome scans, we would still need phenotypic data and pedigrees.

What's the one thing we do when we have an intellectually delayed child with an abnormal CMA/CGH? We test the parents. Looking for THEIR phenotypes to make sense of the genome mess.

Look, people always give me reasons why the genome is important and a family history is useless.
I've heard them.

-"We don't speak with that side of the family"
-"My father lived with his uncle, because his father died (secretly running the empire as Darth Vader)"
-"I was adopted by Bail Organa, only to find out I have a lost twin brother"

There is one thing that will always be certain over time, there will be some screwed up family dynamics making it difficult (BUT NOT IMPOSSIBLE) to obtain an accurate family history.

That being said, it is still often useful to capture those who you can. And still less expensive.

I look forward to the briefings from this conference, and Muin, if you are listening, I would love to have the link to the webcasts.... Oh wait, they have that too! Sweet.

If you can't be there, you can get the information you seek!

Once again, we need a state of the science on genome prediction, not a consensus statement a real eval of the state of the science. When placed side by side with the state of the science for a family history, we will soon see why family history is the preferred screening tool and will likely to continue that way, perhaps in conjunction with a genome scan, but genomes will NEVER replace family history.

The Sherpa Says: The press better be at this conference and report on Family History. And to the founders of Geni.com, you missed on this one when Tindall presented to you. Or maybe you just are going to steal the idea.........

Gene Genie is Back at The Sherpa!

There are many posts that were submitted. I have to say, we are doing a good job of covering these genes, but probably won't get through them all. I am excited about a ton of this content. But when we move through genetic discovery, talk always falls back to personalized medicine. I have been trying to move away from this term lately. And so has the American College of Medical Genetics. I like the term Genomic Healthcare. It's simple and expresses what is going on today and what will continue for the next decade or two.

So without much ado let's get started!

First the basic science. It is on the shoulders of these giants which Sherpas like me stand when we implement the clinical action. We are all different, every single one of us unique. What makes us this way? Well Yann Klimentidis shares with us some of his thoughts on the SNPs and genes that may make each population special. How can we trak what population you are from? Well, one good way is through mitochondria and now we have a more visual way to look at the mitochondrial genes. Made by a "mitochondrialist" (I would love to see what that conference looked like) the MitoWheel is poised to help those who need just a little more visual model.....May the Force Be With You.

At least if you have blue eyes, then things are looking up. Blaine over at Genetic Genealogist covers that family tree. Now I bet Tom Cruise doesn't feel as special anymore.

Other things make us special. The stuff with which we arrogantly called junk, including introns is proving to make us pretty special. Larry at Sandwalk elegantly covers some of the hot topics in Intronic Junk. This makes him the Tony Soprano of genetic waste management! Nice post.

It's not all about the Homo Sapiens. Even birds get their say at GrrlScientist where the argument for earlier flight is posed. Not really a gene post per se, but it is a Rock vs DNA clock battle. Speaking of evolution, what makes a fish go blind and how do they get that sight back? Greg Laden's blog will show you how. Better blind than dead, but if I have to go, I would like to skip the Black Death. Especially after reading Archeozoology's coverage of the Yersina Pestis Genome. Well maybe I will eat myself to death...or a higher level of evolution. Nature Blogs cover the Big Mac controversy. Nature versus Nurture debate will never end!

So how do we take this to the road? How can we translate these unique findings?
First we have to educate the physicians and get them up to speed. But can we do it? I will be presenting at the Association of Program Directors in Internal Medicine precisely on this topic. The blog PredictER gives some insight as well. Some may say we should just bypass physicians, let's here about our Genetic Future. After that good laugh we can head to Berci Mesko at Scienceroll and find a "23 and Me Hacker" who has created a pretty useful tool to help.

We all know that these technologies will only continue to improve. Unfortunately most MDs don't have the time to keep up. Here's a hint for them....Visit the Gene Genie, which will be at Sciencebase next.

For those who need a quick set of new tests!
deCode first with the PrCA gene, cute fellas, real cute. Hsien and Ramunas both cover this one.
Soon we won't need all of these tests. Especially if the 1000 genomes projects get things scanned quickly. I am certain all sorts of novel technology will be created. This will shake things up.

Until that day we have Family History. I was with a patient and one of our geneticists today. When a patient asked him how many patients he had seen he said "I have been doing this counseling before they even had the test." In heart attack land, family history is still the king predictor of MI risk. But I doubt that the company selling the Kif6 test want you to know that. Well maybe someday I will show up on the WSJ health blog too.....

Thanks to all those who submitted. I hope you enjoyed this. Thanks to Ricardo at MyBiotechLife for the excellent logo!

Pharmacogenomics Rising

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

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

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

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

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

I want my Genome!! What about your cholesterol?

Today I read something that blew me away! While Myriad is hammering away on NYC TV to get your BRCA test. 10-15% of all breast cancer patients have BRCA mutations in either 1 or 2. These tests cost over 3000 USD a piece, even worse, there are very few clinical changes that result from positivity of either mutation.

The stat that hit me like a punch in the nose was "80 per cent of women in the US between 18 and 44 don't know their cholesterol level" I couldn't believe it! This according to a recent survey by the Society for Women's Health Research (SWHR). This non-profit agency "encourages the study of sex differences between women and men that affect the prevention, diagnosis and treatment of disease".

This is what I find funny. A patented gene test can have a multi-million dollar ad campaign, but women's heart health gets barely a whisper. Despite heart disease being a much bigger killer in women. If you thought carrier status for breast cancer was a big deal. Having an elevated cholesterol is the closest thing to having a heart attack. Even worse, there are some simple preventative things you can do for cholesterol and it doesn't include surgery or medications.

So while we all bask in the glory of The Personal Genome Project and 23andMe, we need to get a grip. Just because you can get your genome sequenced, doesn't mean it will tell you your cholesterol level. Clinical acumen is what is required for personalized medicine, not technology alone.

The Sherpa says: According to this study "More than half of the women 18-44 surveyed were concerned about cholesterol, but the vast majority weren’t aware of their personal cholesterol level and one-quarter did not even know how cholesterol is tested" Why? Because we don't have Quest lab reps stopping by your PMDs office telling you that you MUST test women's cholesterol. That means asking your physician to check your cholesterol is up to you!

Gene Genie and George's Blog

First....Gene Genie is up at Cancer Genetics. Thanks to Ramunas who put up an excellent edition!!

Second and even more importantly......My excellent Chief of Genetic Counseling brought George Church's blog to my attention. My gosh....

His evaluation is right on point. His question is a wonderful one...... Great now we have genomes....so what. How do we get to systems biology? Once we have systems biology on point, we will then have truly personalized medicine. We will be able to manipulate the systems....and physicians will become engineers, systems analysts....

So when will we get there? How will we get there? My gut says there are 25 different signalling systems and perhaps four different common pathways....these will corroborate with the 4 humours........ Welcome back Galen and great to see you again Hippocrates.

The Sherpa Says: Stick around for 2010 it's gonna be huge! I am a firm believer in systems biology. I feel that be understanding cellular signalling pathways, we will see the link between previously unrelated disease. For an example if this take a look at this NYT article.

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)?

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 interviewed.


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.

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

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.

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?

Gene Genie: a Famous Blog Carnival’s Sixth Issue

Gene Genie is at ScienceRoll today. If you don't know what the Carnival is find out more here

Bertalan Meskó includes some interesting videos that I hope to include in my curriculum for residents (They are perfect for our residents' capability) LOL :)

This is a great Carnival filled with interesting tidbits so I suggest you take a look.

Great Job Dr Mesko! Check out his post on Web 2.0 and Medicine 2.0 It is prescient and is the path towards genomic education and personalized medicine.

Have a great week

-Steve