Breakthrough of the year 2013 and runners-up

First post of the year, and as last year, I will make it an overview of the ten scientific accomplishments of 2013 the editors of Science deemed the most notable of the year. Lots of biology on the menu!

Breakthrough of the year: cancer immunotherapy

Last year celebrated the discovery of the Higgs boson. Announced in July 2012 by researchers from the European particle physics laboratory (CERN), it was described as the final missing piece to the standard model of fundamental particles and forces.

The 2013 breakthrough is not quite the same kind of breakthrough: not a recent single find that carries a high degree of certainty, but rather the beginning of the validation of a treatment strategy for cancer that originated in the 90s. Cancer immunotherapy is certainly not a magic bullet against cancer, and there is a lot that remains to be understood. However, it represents a new and promising way of engaging the fight against cancer: instead of targeting the tumor directly, the aim is to modify the patient’s own immune system to help it get rid of the tumor.

The development of cancer immunotherapy is rooted in fundamental research that painstakingly increases our understanding of human biology. Understanding the biology of tumors and why our immune system sometimes fails and lets harmful, cancerous cells develop is crucial to the development of new therapeutic strategies, but sometimes, advances may also come from research not directly related to cancer.

One of the examples of cancer immunotherapy mentioned in the Science piece is an antibody targeting a molecule called CTLA-4 (cytotoxic T lymphocyte antigen 4). This molecule is present on the surface of immune cells called T cells and acts as a kind of brake, limiting the extent of immune attack these cells can mount. Discovered in 1987, it was not until 1996 that experiments showed that antibodies specifically recognizing this protein could help shrink tumors in mice. It then took a bit more than a decade – and the involvement of a small biotech company and a large pharmaceutical company – to develop a cancer treatment strategy for humans based on these findings, and subsequently report the first promising results in a randomized controlled trial in patients with advanced melanoma.

Since cancer immunotherapy is not per say a sudden breakthrough, but a long and difficult development process, why was it chosen by the Science editors as the 2013 breakthrough? Their argument is that the number of clinical trials showing promising results has now reached a point that fully supports the potential of immunotherapy to improve on current cancer treatment strategies. The number of cancer patients who have benefited from immune-based therapies is still small, and the benefits themselves may be limited, but the idea of empowering a patient’s own immune system to fight off cancer is one that opens up many new avenues. From therapeutic cancer vaccines teaching the immune system to recognize and kill tumor cells to antibodies releasing the brakes on immune cells to allow them to mount full-blown attacks, the hope is to find more effective therapies, and ones that will carry fewer side effects (a non-negligible improvement on currently available cancer treatments).

How large the impact of immunotherapy will be on the management of cancer remains to be seen, but at least it is offering hope for the development of new therapeutic strategies.

If you want to read more on the subject, the Science article can be found here, and Nature has a whole supplement on the topic (free access for both).

Runners-up

– a new genome-engineering tool, called the CRISPR/Cas system.

While last year’s list of runners-up made note of TALENs, nucleases that could cut with high precision in chosen specific areas of the genome, 2013 saw the rise of yet another high-precision high-efficiency DNA cutting tool allowing for fine editing of genomes, from bacteria and yeast to fruit fly, mouse and human cells: the CRISPR/Cas system. To give some perspective to the reader who has never tried to insert/modify/delete a particular gene in, say, a mouse genome (not just because one can, but as a way of understanding what this particular gene might do in the life of a cell, tissue and whole organism), it is good to remember that just 10 years ago, researchers could not readily control where in the genome they could insert or delete a piece of DNA.

(For a bit more reading on TALENs and CRISPR/Cas, here is a short post I wrote about a year ago.)

– a new brain-imaging technique, called CLARITY, that allows to literally see through a mouse brain (post-mortem) while leaving intra- and inter-cellular structures in place and amenable to traditional labeling methods to identify specific proteins and cell types

– the increasing recognition that the bacteria living within the human body, called the microbiota, play an important role in health and disease, from their influence on immune system function to their involvement in the development of malnutrition and obesity

– evidence that beyond affecting our memory, metabolism and immune system, sleep plays a crucial role in helping “cleaning” and repairing the brain

perovskite, a cheap and easy-to-make solar cell material, capable of converting more than 15% of incoming sunlight energy into electricity (better than current solar cell technologies), and that may possibly be coupled to conventional silicon solar panels to achieve an efficiency as high as 30%

– and: the growth of rudimentary “mini-organs” in a culture dish from pluripotent stem cells, the use of structural biology data to design effective vaccines against viruses particularly good at evading attacks from the immune system, the derivation of embryonic stem cells from a cloned human zygote, and the tracing of cosmic rays back to their source in the remnants of supernovae.

For more about all these scientific advances, directly from the source, check out the Science special issue “Breakthrough of the year 2013” (20 December 2013 vol 342, issue 6165, pages 1438-1439).

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