Genomics 

It is my weekend off. It is now Saturday night. My son had a pool party and invited his baseball team over. They all had a great time. For pool safety, I made a shepherds hook, so that was good. My wife did a ton of work and created a great party not only for the kids, but for their parents as well. I mowed the lawn in the morning, and that is something that I really like doing. 

So, its now evening, and  I picked up my May issue of Scientific American magazine and started reading it. This is my favorite magazine. I have read every issue since high school. SA magazine publishes stories about new science and technology. SA publishes things like "Orville Wright built a machine that flies", or maybe "Watson and Crick discover DNA", or maybe "penicillin kills germs in living people". SA publishes many things that change the basic fabric of life and society itself. That is probably why is is the longest continuously published magazine in the world. 

So I got to an article in this issue that stopped  me in my tracks. I think it has changed all of our futures in an unbelievably positive manner. This may not be as important as, say, inventing language, but it is up there with inventing the wheel, or maybe fire. This changes everything in medicine, if true. Lets give you some important background. 

As I noted in some of my prior posts, I will offer BRCA testing to my patients if I believe that they are at high risk of carrying the BRCA mutation. I will note this patients family and personal history, and if it suggests the gene might be there, then I ask the patient to go through the process of getting the test. The test costs thousands of dollars. If it is negative, the patient cannot rest easy, because she still has a giant set of risk factors for cancer. But if the BRCA test is positive, then the risk is off the scale. She needs to have her breasts and ovaries removed as soon as she is done with them. For her, the risk of breast cancer may be as high as 95 percent. So, the BRCA test can easily save her life. And, more importantly, save the life of her children's mother (that was a play on words, I hope you all get it). For the monetary cost of a few thousand dollars, I get to assess this patients risks for cancer. The company that does this genetics testing is called Myriad Genetics and they provide great services to me and my patients. 

Myriad's price is thousands of dollars for the few genes of BRCA. Imagine the cost of sequencing an entire human Genome. The US government sponsored the first human genetic sequencing, at a cost of 3 billion dollars. The first rough draft was finished in 2000. The final result was published in 2003, covering about 92 percent of the human genome. But there was giant competition at the same time. Private companies were racing do the same thing.  The private companies were planning to "patent" the genetic information. Any company that "patented" a gene, could dictate what use was made of that information. And make billions of dollars. But President Clinton got involved. 

President Clinton made an announcement in March of 2000 that the "human genome sequence" could not be patented. I don't think anyone knew if he was correct or not. But in two days, the market valuation of biotech companies dropped by 50 billion dollars.  I, for one, agree with President Clinton on this. How can a company claim ownership of everybody's  DNA? That doesn't make sense to me. 

So the situation up until 2009 or so was that genetic sequencing was astronomically expensive. As of 2009, a total of about 7 humans have had their DNA sequenced. Then it all changed. 

One day, a genius named Jonathan Rotherberg had a stroke of inspiration. His child was sick in the ER (casualty department) and the doctors told him it may be his child's genetics. What the doctors presumably didn't know was that he ran a genetics company. This company was in the business of mining the public knowledge of gene sequences, and making useful medical technology. But Rotherberg had an inspiration while sitting in the ER. He saw a photograph of a new and modern computer chip made by Intel corporation. He already knew that gene sequencing was an expanding science, but the expansions were conducted by making more machines, not by making machines more efficient. 

So he, somehow, made a gene sequencer on CPU chips. It really works. And it is really really small. The first chips had a few hundred sequencers. The new ones have 10's of thousands. These chips cost as little as 99 dollars. With these chips he can sequence any given human in 8 hours. This persons genome can then be stored on a 1 dollar DVD disk, or on a 5 dollar thumb drive. 

Where we stand now is that with these efficient chips, a human can get their own genome. 

He sequenced himself and found out that he was a carrier of the BRCA gene. So now, his daughters are aware, and they can get the BRCA test for themselves. It's 50/50 whether they get it or not, as that probability is simple genetics theory. And, if his daughter has it, they can get their breasts removed when they are done with them (and, hopefully, get replacement breasts that don't cause cancer). 

Scientific American magazine actually felt the need to put it a disclaimer that these tests have not been approved by the FDA for clinical use. I think the disclaimer is a damn shame. I don't think that anyone cares if the information is approved or not. I think that if the test shows that a person has a known mutation, that shows a risk for cancer, then that person is going to act. That person may get the traditional, approved test. But that person will, and should, protect themselves somehow. 

What is really important is that for one third the price of a single mutation test, that person can be tested for all known genetic diseases. 

In the last three years the number of people who have had a gene sequence of themselves done has gone from 7 total to about 30 thousand. 

I think the days of testing for a single mutation are coming to an end. 

What we will have instead is the genome, and then a computer search of that persons DNA for known disease causing mutations. It will be much simpler testing. Although the interpretation of risk factors will continue to require judgement and analytical thinking. It is likely that the job of a geneticist will continue to expand. Their jobs will not go away, but become even more important through the years.  

Then, what will really be interesting will be the correlation of diseases with DNA. Ultimately, we will be able to find the DNA basis of diseases that don't yet have known genetics. 

For instance, if we get a database of people with Multiple Sclerosis, and then compare that database with people who don't have MS, we will easily find the genetics differences. That is a trivial computer search. Once we have the gene, then we can have the protein the gene encodes, and we will be that much closer to a cure. 

Cancer is an even bigger target. Cancer is a genetic disease in that the cells of the tumor appear to have tremendous damage to their DNA. If we can sequence the DNA of the tumor, we can target the therapy to that particular tumor. Since cancer drugs can cost hundreds of thousands of dollars, and many times they don't even work, we have a giant opportunity to use far more effective therapies These therapies may avoid dangerous or ineffective therapies, thereby saving maybe hundreds of thousands of dollars, and much risk for the patients. 

The company that created the DNA sequencer on a chip is called Life Technologies. Life Technology corporation has chosen to display their sequencing technology at the latest Consumer Electronic Show in Las Vegas. They are there alongside the televisions and stereos. Life Technology calls it the "Ion Proton Sequencer". PC magazine calls it the "coolest thing I saw" at the show. You can read it at http://www.pcmag.com/article2/0,2817,2398817,00.asp. It seems to me that Life Technology wants to get this technology out in front of the face of the general public. 

That works for me. 

If I was Warren Buffet, I would put my money into this company. 

The era of "molecular medicine" has begun. 

What I mean by this is that a person can now be analyzed down to the level of the individual proteins that make them up. This information can be carried around on a key chain and used when the genetics go awry, such as in cancer. 

We can even sequence fetuses (feti?) in utero with some simple in utero testing such as Amniocentesis or CVS. 

I think the day is close when I can order a DNA sequence for a patient of mine. This will reveal the entirety of their genome, all 46 chromosomes, all 30 thousand or so genes, mutations and all. 

Paternity testing will be trivial. As will all mutations and known variants. And exploring for the unkown genetic basis of disease will be trivial . 

Thanks for reading my blog. 

I hope everyone enjoys reading it as much as I enjoyed writing it. 

Please provide feedback one way or another. 

I think my next post will be about contraceptive options. In my opinion, women are frequently making sub optimal choices. I will try to describe why women are making sub optimal choices. And we will try to make better choices. And we will try to describe how to watch out for risks, and mitigate real risks. 

Of course, if there is something else anyone wants me to write about, just let me know somehow. 

And anyone is welcome to call for an appointment

And also, I would like to welcome my first reader from Persia. Iran is a giant contributor to the history of science, and I am glad to see that they are here reading my blog. I hope you find it useful. 

Thanks Sincerely, 

Dr John Marcus Ob/Gyn 

Ridgewood, NJ 07450 

phone 201-447-0077 

fax      201-447-3560 

unofficial website at www.doctorjohnmarcus.com

blog at doctorjohnmarcus.blogspot.com 

business website at www.lma-llc.com