Articles in 2013

Biomedical research in 2013 saw some dramatic developments, with unprecedented government action in the US ranging from the budget sequester in the spring to a dramatic government shutdown in autumn. But throughout the year, bright spots in science around the globe continued to dazzle, including multimillion-dollar partnerships to advance drug discovery and the go-ahead for highly anticipated trials of regenerative medicine.

As immunotherapies and even newer strategies such as antisense therapy march ahead, the drug development pipeline took an interesting turn this year. Here, we look back at the compounds that made the cut, as well as those that got cut.

Despite metformin being one of the most commonly prescribed drugs for the treatment of diabetes, how it elicits its therapeutic effects has remained mysterious. A new study in mice shows that inhibitory phosphorylation of acetyl-coA carboxylases Acc1 and Acc2 by the AMP-activated protein kinase (AMPK) is essential for the ability of metformin to improve insulin sensitivity and lower blood glucose in obesity (pages 1649–1654).

From the microbiome to the microenvironment, certain areas of biomedicine saw fast-paced discovery this year. Here's a rundown of the papers that helped these fields advance quickly in 2013.

High blood ammonia, as seen in severe liver disease and urea cycle disorders, is neurotoxic and difficult to treat. A new study shows that the toxic effects are caused by impaired astrocyte potassium buffering—not astrocyte swelling, as previously thought—and can be partially blocked by the diuretic bumetanide (pages 1643–1648).

Although stem cells were initially thought to be the magic bullet for numerous diseases, translation of a stem cell–based cure into the clinic is still a work in progress. Basic research is shedding light into the potential of stem cells, and different research fronts are now exploring how to exploit this potential to tackle diverse conditions. In 'Bench to Bedside', Akemi Tanaka, Mark Sauer, Dieter Egli and Daniel Kort discuss how genome transfer from eggs of mothers with mutated mitochondria into an enucleated egg from a healthy female donor at an early developmental stage can eliminate mitochondrial disease. The negligible mutant mitochondrial DNA carryover and the differentiation of subsequent embryonic stem cells into various cell types with healthy mitochondrial DNA content suggest this could be used to prevent transmission of mitochondrial disease to the offspring. The authors discuss safety concerns and remaining technical questions that need to be resolved to make way for this new technology in the clinic. In 'Bedside to Bench', Nan Yang and Marius Wernig peruse a small study of children with a myelin disorder showing that transplantation of human neural stem cells leads to engraftment and donor cell–derived myelination.

Advocacy for the integrity of the scientific record is stronger than ever. Paradoxically, retracting a flawed paper is getting more and more difficult.

This year saw the launch of the Global Health Innovative Technology (GHIT) Fund—a new public-private partnership between five Japanese pharmaceutical companies, two government ministries and the Bill & Melinda Gates Foundation. In November, the Tokyo-based fund announced its first round of awards totaling $5.7 million. Leading the new $120 million, five-year initiative is BT Slingsby, a US-born scholar of the Japanese healthcare industry. He met with Cassandra Willyard to discuss the new fund and how Japan can help drive the development of medicines and vaccines for diseases of the developing world.

Our list of newsmakers this year includes everyone from thought leaders with brainy plans for the future to individuals who influenced rules and regulations—even from beyond the grave.

Enabling women to serve at the highest leadership levels in pharmaceutical R&D will help advance science to offer a broader array of medicines to patients. But in an industry dominated by men in the most senior-level roles, women have a long way to go to get to the top.

Cell-mediated activation of latent TGF-β1 is a key promoting event in fibrosis in all organs. A new study shows that specific targeting of the αv subunit of integrins in fibrogenic myofibroblasts effectively reduces developing and established fibrosis in liver, kidneys and lungs (pages 1617–1624).

Co-working spaces in which many entrepreneurs share a common environment have been a hallmark of the computer startup industry for decades. Now, the life sciences sector is beginning to do the same. Elie Dolgin talks with the pioneers helping to bring affordable wet-lab space—plus the infrastructure and support needed to launch a successful commercial enterprise—to the next generation of biotech innovators.

The blood-brain barrier (BBB) has a key role in maintaining brain homeostasis and, thus, brain function. This Review outlines recent advances in understanding the development and maintenance of the BBB and the contribution of BBB disruption to various neurological diseases. It also discusses how such insights might be used to design new therapeutic strategies for BBB repair.

Adjuvants play an important part in vaccines, as they can enhance and shape antigen-specific immune responses. This Review discusses the benefits of adjuvants and recent advances in understanding their mechanisms of action. The authors also set out the clinical barriers to development of new adjuvants and offer suggestions for overcoming these hurdles to the advancement of next-generation vaccines.

Cancer stem cells are thought to be resistant to anticancer therapies and are able to repopulate tumors and sustain tumor growth. The authors establish BMI-1 as a crucial regulator of cancer cell stemness in colorectal tumors and develop a chemical inhibitor that targets cancer stem cell renewal by reducing the levels of BMI-1. This strategy affords antitumor effects in vitro and in vivo and may pave the way for the precise targeting of elusive cancer stem cells.