NIH-Funded Research Makes Science’s “Top 10” List

Posted on January 6th, 2015 by Dr. Francis Collins

Modeled after Time’s Person of the Year, the journal Science has a tradition of honoring the year’s most groundbreaking research advances. For 2014, the European Space Agency nabbed first place with the Rosetta spacecraft’s amazing landing on a comet. But biomedical science also was well represented on the “Top 10” list—with NIH helping to support at least four of the advances. So, while I’ve highlighted some of these in the past, I can’t think of a better way for the NIH Director to ring in the New Year than to take a brief look back at these remarkable achievements!

Youth serum for real? Spanish explorer Ponce de Leon may have never discovered the Fountain of Youth, but researchers have engineered an exciting new lead. Researchers fused the circulatory systems of young and old mice to create a shared blood supply. In the old mice, the young blood triggered new muscle and more neural connections, and follow-up studies revealed that their memory formation improved. The researchers discovered that a gene called Creb prompts the rejuvenation. Block the protein produced by Creb, and the young blood loses its anti-aging magic [1]. Another team discovered that a factor called GDF11 increased the number of neural stem cells and stimulated the growth of new blood vessels in the brains of older animals [2].

These intriguing experiments have led to clinical trials that are exploring the impact of plasma from young people on middle aged and elderly Alzheimer’s patients. If the results are positive, this could mark a turning point for the study of diseases of aging.

Cells that might cure diabetes. A team in Boston figured out how to transform human embryonic stem cells and human-induced pluripotent stem cells (created from reprogrammed skin cells) into insulin-producing beta cells, a potentially major advance for people with diabetes. Not only did the cells look like healthy beta cells, they functioned like them in a mouse model of type 1 diabetes, restoring abnormal blood glucose levels to normal [3].

Before these cells can be transplanted into patients, however, researchers need to reproduce the results and extend them to humans. Another challenge for using these cells to create an “artificial pancreas” to treat diabetes? Finding a way to shield the insulin-producing beta cells from the unwanted “friendly fire” of the immune systems of people with type 1 diabetes.

Manipulating memory.  It’s no secret that many of our memories are associated with feelings, some good and some not-so-good. Why is this? In 2014, as part of an ongoing quest to explore how memories are shaped and reshaped, researchers were able to identify the brain circuits that link memories to both positive and negative emotions, at least in mice. In a technical tour de force, the researchers went on to use a technique that uses light to control the activity of brain cells, called optogenetics, to change the emotions associated with the mice’s memories from negative to positive (in this case, fearful to pleasant) and vice versa [4].

And there are many other examples from 2014 of neuroscientists making progress in understanding the molecular mysteries of memory. For example, another group recently used optogenetics to silence a subset of neurons in the brains of mice, preventing the animals from recalling a frightening event and effectively erasing their memory of it [5]. Although optogenetics is too invasive to use in humans, what is learned from such research could help point the way to more effective treatments for a range of mental illnesses, including depression, anxiety, and post-traumatic stress disorder.

Giving life a bigger genetic alphabet. All life on earth is encoded in the same four-letter alphabet of DNA chemical bases: adenine (A), cytosine (C), thymine (T), and guanine (G).  Now—or at least in the laboratory—scientists have added two synthetic chemical bases, X and Y, to the language of life. The new chemical bases pair with each other and incorporate into the double helix alongside the A’s, C’s, T’s, and G’s. The researchers have shown that bacteria engineered with these synthetic building blocks can replicate in the test tube, passing on this expanded genetic code to the next generation of bacteria [6].

At present, X and Y do not encode any protein-building amino acids. But researchers intend to create a toolbox of synthetic amino acids that can be incorporated into designer proteins and biomaterials for medicine or industry. If the thought of these artificial life forms unsettles you, rest assured that these bacteria couldn’t replicate outside the lab because X and Y don’t exist naturally in the environment.

Areas to Watch in 2015. Science—like NIH—isn’t content to simply look back at past achievements. The journal’s editors also have a tradition of looking ahead at what fields of research may yield exciting breakthroughs in the coming year.

One particular area of research that Science thinks we should keep our eyes on in 2015 is combined immunotherapy. In this approach, cancer patients receive one therapy that spurs their own immune systems to attack cancer, plus a targeted drug therapy and/or radiation. This potentially powerful strategy is currently being tested in clinical trials for a wide range of cancers, including melanoma and lung cancer. The hope is that by precisely combining different kinds of therapeutic strategies, we may be able to match patients up with more effective strategies for curing or controlling their cancers over the long term. If so, it will be a happy new year indeed!

References:

[1] Young blood reverses age-related impairments in cognitive function and synaptic plasticity in mice. Villeda SA, Plambeck KE, Middeldorp J, Castellano JM, Mosher KI, Luo J, Smith LK, Bieri G, Lin K, Berdnik D, Wabl R, Udeochu J, Wheatley EG, Zou B, Simmons DA, Xie XS, Longo FM, Wyss-Coray T. Nat Med. 2014 May 4.

[2] Vascular and neurogenic rejuvenation of the aging mouse brain by young systemic factors. Katsimpardi L, Litterman NK, Schein PA, Miller CM, Loffredo FS, Wojtkiewicz GR, Chen JW, Lee RT, Wagers AJ, Rubin LL. Science. 2014 May 9;344(6184):630-4.

[3] Generation of Functional Human Pancreatic β Cells In Vitro. Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton Cell. 2014 Oct 9;159(2):428-39.

[4] Bidirectional switch of the valence associated with a hippocampal contextual memory emgram. Redondo RL, Kim J, Arons AL, Ramirez S, Liu X, Tonegawa S. Nature. 2014 Sep 18;513(7518):426-30.

[5] Cortical Representations Are Reinstated by the Hippocampus during Memory Retrieval. Tanaka KZ, Pevzner A, Hamidi AB, Nakazawa Y, Graham J, Wiltgen BJ. Neuron. 2014 Oct 22;84(2):347-54.

[6] A semi-synthetic organism with an expanded genetic alphabet. Malyshev DA, Dhami K, Lavergne T, Chen T, Dai N, Foster JM, Corrêa IR Jr, Romesberg FE. Nature. 2014 May 15;509(7500):385-8.

NIH Support:

Breakthrough 1: National Institute on Aging; Office of the Director; Common Fund; National Heart, Lung, and Blood Institute; National Institute of Neurological Disorders and Stroke

Breakthrough 2: National Institute of Diabetes and Digestive and Kidney Diseases

Breakthrough 3: National Institute of General Medical Sciences, National Institute on Aging

Breakthrough 4: National Institute of General Medical Sciences