Skip to content

When you choose to publish with PLOS, your research makes an impact. Make your work accessible to all, without restrictions, and accelerate scientific discovery with options like preprints and published peer review that make your work more Open.


Precision Medicine Initiative – Ricki’s Pick for Breakthrough of the Year

‘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, in 1989 and 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.

20150429-gene_editing-tech“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. It is certainly deserving, but something of a head scratcher to me in that 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 of CRISPR-Cas9 technology. But its roots go back to the late 1980s, and it will still 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. (My book on gene therapy chronicles the history, and the example that drives the narrative is likely to be that first approval. Stay tuned.)

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.

The president 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. In a nutshell, 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 a big part of the PMI, the Cohort Program, summarized here at DNA Science, was published a few days before the annual meeting of the American Society of Human Genetics in October. There, 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.”

ATCG's Image with Group of PeopleThe freaking out has likely slowed as the PMI hit the news again this week — maybe some of the leaders will weigh in here. 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 in the new year.

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

The PMI covers a lot more than genes, and one route to precision medicine is decidedly low-tech: listening to the patientPersonalized 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 non-precision medicine.

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 vast. 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.

A diagnosis should account for a patient's activity level.
A diagnosis should account for a patient’s activity level.

2. My husband’s slow heart rate has been deemed abnormal – unless the health care practitioner is also a long-time, long-distance runner.

3. I just switched primary care providers and asked for a refill of ibuprofen. The nurse asked why – osteoarthritis – but then informed me about ibuprofen causing stomach upset. I pointed out that that only happens to about 2 percent of people with arthritis using the drug, and not to me, since I’ve been taking it for years. Nonetheless, 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 co-morbidities that suggest the risk would outweigh the benefit.

Statin_Risks_(6941350219)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 critical 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, to the point of fainting easily. Pathology is not normalcy.

(Ernesto del Aguila, NHGRI)
(Ernesto del Aguila, NHGRI)

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 a more personalized approach to population screenings and common health concerns!

I suspect CRISPR-Cas9 will indeed overshadow the PMI in the end-of-year top science stories lists. But I share Dr. Collins’ enthusiasm, if not my 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.”


Leave a Reply

Your email address will not be published. Required fields are marked *

Add your ORCID here. (e.g. 0000-0002-7299-680X)

Back to top