Happy New Year: Looking Back at 2016 Research Highlights
Posted on by Dr. Francis Collins
Happy New Year! While everyone was busy getting ready for the holidays, the journal Science announced its annual compendium of scientific Breakthroughs of the Year. If you missed it, the winner for 2016 was the detection of gravitational waves—tiny ripples in the fabric of spacetime created by the collision of two black holes 1.3 billion years ago! It’s an incredible discovery, and one that Albert Einstein predicted a century ago.
Among the nine other advances that made the first cut for Breakthrough of the Year, several involved the biomedical sciences. As I’ve done in previous years (here and here), I’ll kick off this New Year by taking a quick look of some of the breakthroughs that directly involved NIH support:
DNA analysis and human migration: I highlighted this intriguing advance on my blog last September. All humans trace their ancestry to Africa. But there has been considerable room for debate about exactly when and how many times modern humans departed Africa to take up residence in distant locations throughout the world.
Three new studies—two of which received NIH funding—helped to fill in some of those missing pages of our evolutionary history [1-3]. The genomic evidence suggests that the earliest human inhabitants of Eurasia came from Africa and began to diverge genetically at least 50,000 years ago. While the new studies differ somewhat in their conclusions, the findings also lend support to the notion that our modern human ancestors dispersed out of Africa primarily in a single migratory event. If an earlier and ultimately failed dispersion occurred, it left little trace in the genomes of people alive today.
What might have driven our ancestors to make such an uncertain migration? We’ll never have the full story. There’s no evidence so far that major genetic mutations would have produced shifts in human traits and behavior since the time of that fateful departure. It’s more likely cultural and environmental changes exerted a selective influence on mating and survival, and so were most likely to be the ultimate driving forces spurring the transformations that made Homo sapiens who we are today.
Better aging by eliminating old cells: As we age, our bodies accumulate cells that senesce, or lose the ability to divide. These worn-out cells don’t settle quietly into their dotage. They secrete large amounts of enzymes, growth factors, and other molecules that seem to have an inflammatory and pro-aging effect on nearby cells.
Last February, a team of NIH-supported researchers and their colleagues used genetically-engineered middle-aged mice to show for the first time that eliminating senescent cells from the body improves health and longevity . Not only did these mice have less age-related deterioration in their hearts and kidneys than other mice, they outlived them by more than 20 percent. Then in October, the team eliminated senescent cells from the arteries of mice prone to atherosclerosis . The result: the amount of fatty, plaque-forming buildup in the arteries was reduced by 60 percent. The research is still in its early stages, but work is already under way to develop drugs that might target senescent cells for a range of conditions, including atherosclerosis, pulmonary fibrosis, osteoarthritis, and kidney dysfunction. In fact, an NIH-supported clinical study of these so-called senolytic drugs is getting under way involving adults and seniors with chronic kidney disease.
Creating novel proteins: Proteins are the building blocks of life. They’re involved in almost everything that takes place in our bodies—from transporting oxygen in the blood to fighting off a bad virus. So researchers have long sought to determine how to design new proteins that might help them do even more to study and treat diseases. Over the past several years, laboratory scientists have made impressive strides in working out how to custom design proteins. Much of this progress owes to the development of better computer programs that more accurately predict how proteins will fold into their complex 3D shapes, a primary determinant of their function.
This progress led in 2016 to a rise in publications presenting unique, made-in-the-lab designer proteins that aren’t found in nature. In February, NIH-supported scientists and their colleagues used one such program to design a potential universal flu vaccine that primes the immune defenses to detect all flu strains at once . In July, some of these researchers and others created proteins that self-assemble into empty cage-like structures, which someday could be filled with drugs or bits of DNA to treat human disease [7,8].
Nanopore sequencing for portable laboratories: The NIH has invested heavily—and continues to do so—in the development of innovative technologies that will expand the use of DNA sequencing in medical research and health care. One of them is called nanopore sequencing. It involves threading single DNA strands through tiny pores in protein membranes that measure 1 to 2 nanometers in diameter. (By comparison, a human hair is 100,000 nanometers in diameter.) Individual base pairs—the chemical letters of DNA—are then read one at a time as they pass through the nanopore. The four unique bases in the DNA alphabet are identified by measuring the difference in their effect on current flowing through the pore.
Nanopore sequencing can be much faster than traditional sequencing approaches. It also could be relatively low cost and offers greater portability for potential use in the field. But nanopore sequencing has taken more than 10 years to develop, and that’s why its recent technological leaps forward are so hopeful. In fact, 2016 brought the first commercial nanopore sequencing device to the market. Researchers also reported using the strategy to sequence a human genome, identify Ebola and other viruses in just a few hours, and decipher the genome of a fungal pest of maize. Astronauts on the International Space Station even got into the act, using it to sequence a mixture of microbes in soil. I had the chance to interview astronaut Kate Rubins about this. In short, applications for nanopore sequencing seem nearly as boundless as the human imagination.
With such great progress in 2016, it’s easy to envision another busy year of breakthroughs in 2017. In fact, Science has already selected some areas of research to keep an eye on in 2017. One is the rapid development of Zika vaccines, about which I blogged quite a bit last year (here and here). Another is the attempt to grow human embryos in lab culture for almost two weeks, opening a new window on development and the early causes of miscarriage.
From my personal list, let me add a big one. This year will see the official launch of the Precision Medicine Initiative’s® All of UsSM Research Program. All of Us will help to build a future in which diseases will be diagnosed and treated with greater precision by taking into account individual differences in patients’ genes, environments, and lifestyles. It’s a truly transformational project, and one that I’d encourage you to consider participating in to build that brighter future.
 The Simons Genome Diversity Project: 300 genomes from 142 diverse populations. Mallick S et al. Nature. 21 September 2016.
 Genomic analyses inform on migration events during the peopling of Eurasia. Pagani L et al. Nature. 21 September 2016.
 A genomic history of Aboriginal Australia. Malaspinas AS et al. Nature. 21 September 2016.
 Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Baker DJ, Childs BG, Durik M, Wijers ME, Sieben CJ, Zhong J, Saltness RA, Jeganathan KB, Verzosa GC, Pezeshki A, Khazaie K, Miller JD, van Deursen JM. Nature. 2016 Feb 11;530(7589):184-189.
 Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Science. 2016 Oct 28;354(6311):472-477.
 A Computationally Designed Hemagglutinin Stem-Binding Protein Provides In Vivo Protection from Influenza Independent of a Host Immune Response. Koday MT, Nelson J, Chevalier A, Koday M, Kalinoski H, Stewart L, Carter L, Nieusma T, Lee PS, Ward AB, Wilson IA, Dagley A, Smee DF, Baker D, Fuller DH. PLoS Pathog. 2016 Feb 4;12(2):e1005409.
 Design of a hyperstable 60-subunit protein icosahedron. Hsia Y, Bale JB, Gonen S, Shi D, Sheffler W, Fong KK, Nattermann U, Xu C, Huang PS, Ravichandran R, Yi S, Davis TN, Gonen T, King NP, Baker D. Nature. 2016 Jul 7;535(7610):136-139.
 Accurate design of megadalton-scale two-component icosahedral protein complexes. Bale JB, Gonen S, Liu Y, Sheffler W, Ellis D, Thomas C, Cascio D, Yeates TO, Gonen T, King NP, Baker D. Science. 2016 Jul 22;353(6297):389-394.
Breakthrough 1: National Institute of Environmental Health Sciences; National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of General Medical Sciences
Breakthrough 2: National Cancer Institute; National Institute on Aging
Breakthrough 3: National Institute of General Medical Sciences; National Institute of Allergy and Infectious Diseases
Breakthrough 4: National Human Genome Research Institute; National Cancer Institute; National Institute of Environmental Health Sciences