icon caret-left icon caret-right instagram pinterest linkedin facebook twitter goodreads question-circle facebook circle twitter circle linkedin circle instagram circle goodreads circle pinterest circle

Genetic Linkage

Precision Medicine Initiative: Ricki's Pick for Breakthrough of the Year

The text you type here will appear directly below the image
‘Tis the season for Science magazine to name their Breakthrough of the Year, a designation that typically irks me because it implies that science happens suddenly and we all know that of course it doesn’t.

The Breakthrough of the Year began as the Molecule of the Year, which began in 1989 inspired by Time Magazine’s Man of the Year, before said magazine realized that half of us are female. Early Molecules of the Year included such celebrities as p53 and nitric oxide.

In 1996 the title shifted to Breakthrough, and embraced technologies as well as molecules, such as full genome sequencing (2000) and cellular reprogramming (2008). A few winners misfired. For example, Wikipedia lists “capturing the promise of youth with stem cells” for 1997’s Dolly the cloned sheep, who actually did not live out a normal sheep lifespan, but I suspect that isn’t the exact wording from Science. It sounds more like a cover line on a fashion magazine.

“Breakthrough of the year” is supposed to honor the “most significant development in scientific research,” and the buzz is that for 2015 it will go to CRISPR-Cas9 used for gene/genome editing. But it’s roots go back to the late 1980s, and the key paper was published not in 2015, but in 2012 and the collaboration that led to it was actually born in late 2011.

The breakthrough for this year could perhaps be the exponential increase in awareness. But it will be years before it hits the clinic. We in the U.S. are, after all, still awaiting the first FDA approval of a gene therapy (which is likely to come in 2016). And those clinical trials started in 1990. And those clinical trials started in 1990. (My book on gene therapy chronicles the history, and the example that drives the narrative is likely to be that first approval).

I’m sure CRISPR-Cas9 will get it’s due as a future Lasker and Nobel, so I’d like to nominate instead for the 2015 Breakthrough of the Year the Precision Medicine Initiative (PMI). Although President Obama has a long-standing interest in genetics, the PMI is a child of 2015.

President Obama announced the PMI at the 2015 State of the Union address, although I’ve yet to meet anyone other than another genetics nerd who’s heard of it. My doctors certainly haven't. The project is “An approach to disease treatment and prevention that seeks to maximize effectiveness by taking into account individual variability in genes, environment, and lifestyle.” It will capitalize on the confluence of next-generation DNA sequencing capabilities, the explosion in information technologies, analysis of the microbiome and epigenetics, and use of wearable devices to monitor physiology.

A 108-page initial report on the PMI Cohort Program, summarized here here, was published a few days before the annual meeting of the American Society of Human Genetics in October, where it inspired the following from NIH Director Francis Collins, blurted at the end of his talk at the start of the conference: “We are all freaked out about all the things that have to get done in the cohort. We at NIH are running around with our hair on fire. This is an opportunity to do something really profound.”

The freaking out has likely slowed as the PMI hit the news again this week. President Obama announced on December 14 that the PMI will get $200 million for 2016, and two days later the NIH called for submission of strategies to start physical exams and collection of biological samples for the cohort-to-be.

Meanwhile, also this week FDA announced its own version of the PMI, PrecisionFDA, but it deals solely with next-generation DNA sequencing and regulation of its applications in genetic testing.

The PMI covers a lot more than genes, and one approach to precision medicine is decidedly low-tech: listening to the patient. Personalized Medicine: Read the Chart!, outlines this approach, wherein I pointed out that had I schlepped a water buffalo to my mother-in-law’s cardiologist appointment, the good doctor would not have noted anything amiss until he finally looked up from his laptop to do the brief physical part of her exam.


Since reading the PMI Cohort Program report, I think about the goals every time I encounter a health care professional who tries to lump me, or a loved one, in with the masses. So here’s a list of 6 recent experiences that illustrate the non-precision medicine approach.

1. I just had a colonoscopy. I’m deemed high-risk, because my father died of colorectal cancer. That was enough info for the nurse doing my intake – dad died of it. But she should have asked my father’s age at diagnosis, and my complete cancer family history, which is extensive. Hereditary nonpolyposis colorectal cancer, aka Lynch syndrome, increases risk for not only colon cancer, but also cancers of the ovaries, stomach, liver, small intestine, uterus, brain, skin, and gallbladder. And age of onset is on average 45, compared to the population mean of 72. My dad was 80 when diagnosed. But no one asked me about Lynch syndrome. Am I really at elevated risk for colorectal cancer? A precision medicine approach, including tests for the appropriate genes dictated by family history, might say no.

2. My husband’s slow heart rate was deemed abnormal – until he said, repeatedly, that he’s been a long distance runner for decades.

3. I just switched primary care providers and asked for a refill of ibuprofen. The nurse asked why – osteoarthritis – but then gave me a lecture about ibuprofen causing stomach upset. I pointed out that that only happens to about 2 percent of people with arthritis, and not to me, since I’ve been taking it for years. That led to pressure to try naproxen – which I know makes me very ill.

4. My 88-year-old mother-in-law was just diagnosed with squamous cell carcinoma. Doc wants it out, because that’s the standard of care – but the patient has highly significant co-morbidities that suggest the risk would far outweigh the benefit.

5. My LDL cholesterol is a little bit on the high side – time for a statin, stat! Both my parents had high LDL, muscle pain from statins, and no signs of cardiovascular disease. Family history is important in interpreting population biomarkers.

6. About a year ago, a health care corporation took over my dentist’s practice and blood pressure screening became mandatory. The hygienist commented, on more than one visit, on how well my hypertension meds were working because my blood pressure was low. I’ve in fact had low blood pressure my entire life. Pathology should not be the norm.

I know these examples are minor -- I'm not talking invasive cancer or cholera. But think of the time and money that would be saved with with a more personalized approach to population screenings and common health concerns!

I suspect CRISPR will overshadow the PMI in the end-of-year top science stories lists. But I share Dr. Collins’ enthusiasm, if not his hair on fire, even if the PMI remains beneath the public radar for now. Precision medicine is long overdue and is indeed “an opportunity to do something really profound".”

(This post is simultaneously published at (DNA Science. Please click to there so it counts! :)).
Post a comment