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I’ve got some exciting news to share with you: as of May 6, 2018, NIH’s All of Us Research Program is open to everyone living in the United States, age 18 and older. That means that you, along with your family and friends, can join with 1 million or more Americans from all walks of life to create an unprecedented research resource that will speed biomedical breakthroughs and transform medicine.

To launch this historic undertaking, All of Us yesterday held community events at seven sites across the nation, from Alabama to Washington state. I took part in an inspiring gathering at the Abyssinian Baptist Church in New York’s Harlem neighborhood, where I listened to community members talk about how important it is for everyone to be able to take part in this research. I shared information on how All of Us will help researchers devise new ways of improving the health of everyone in this great nation.

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Blood sample for PT INR test, diagnosis for coagulation disease

Caption: Finding the right dose of the drug warfarin can be tricky, even with this standard test to measure how fast a person’s blood clots.
Credit: Thinkstock/jarun011

Every year, thousands of older Americans require emergency treatment to stop bleeding caused by taking warfarin, a frequently prescribed blood-thinning pill. My own mother received this drug in her later years, and her doctors encountered significant challenges getting the dose right. The problem is too much warfarin causes potentially serious bleeding, while too little leaves those who need the drug vulnerable to developing life-threatening clots in their legs or heart. The difference between too little and too much is distressingly small. But what if before writing a prescription, doctors could test for known genetic markers to help them gauge the amount of warfarin that a person should take?

Such tests have been available to doctors and patients for a few years, but they have not been widely used. The recent results of a national clinical trial offer some of the most convincing evidence that it’s time for that to change. In this study of 1,650 older adults undergoing elective hip or knee surgery, patients whose genetic makeup was used to help determine their dose of warfarin were less likely to suffer adverse events, including major bleeding. This trial marks an encouraging success story for the emerging field of pharmacogenomics, the study of how the variations in our genes affect our responses to medicines.

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Posted In: Health, Science

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Girl in a lab

Caption: One of the many faces of NIH-supported innovation, Stanford’s Christina Smolke is exploring how synthetic biology and microbes can be used to produce new drugs. She is a 2012 Pioneer Award winner.
Credit: Linda Cicero/Stanford News Service

High-risk research isn’t for the faint of heart. It’s for fearless researchers who envision and develop innovative projects with unconventional approaches that, if successful, may yield great leaps in our understanding of health problems and/or biological mechanisms. It takes nerve and creativity to conceive such projects—and, often, special support to bring them to fruition.  And, as the name implies, there is a significant chance of failure.

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Medicinal chemists are the molecular architects of the drug development world—they do whatever it takes to design and build compounds with therapeutic potential. They are precise, they handle toxic chemicals under extreme conditions, they are continuously developing new structures, and they don’t rest until the job is done.

photo of a spoon suspended over a small paper cupThese chemists begin with an organic chemical “scaffold” (generally made up of carbon, hydrogen, oxygen, nitrogen, and a few other atoms) and then tinker; they often create hundreds of incrementally different versions of the same structure, adding a side chain of additional atoms here or there, to improve the potency or selectivity of the drug. It is painstaking, costly research.

That’s why the new “toolkit” developed by NIH-supported researchers at The Scripps Research Institute in La Jolla, CA, and featured in the November 28th issue of Nature, is such a big hit [1]. The researchers have created a collection of 10 new recipes that can be used to modify “heterocycles”—flat, ring shaped molecules made of carbon and nitrogen that are the building blocks for many drugs. The presence of nitrogen traditionally makes these heterocycles very uncooperative—they are difficult to dissolve and frequently deactivate the reagents or catalysts with which they are supposed to react. Until now adding a branch to one of these molecules could take days or even weeks, at the cost of thousands of dollars per gram (just for comparison, a gram of gold is currently worth about $55).

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