Science journal’s top 10 breakthroughs, 2013
“Ultimately, we concluded, cancer immunotherapy passes the test. It does so because this year, clinical trials have cemented its potential in patients and swayed even the sceptics. The field of cancer immunotherapy hums with stories of lives extended — the woman with a grapefruit-size tumour in her lung from melanoma, alive and healthy 13 years later; the 6-year-old near death from leukaemia, now in third grade and in remission; the man with metastatic kidney cancer whose disease continued fading away even after treatment stopped,” notes a paper published recently in the journal that ranked the top 10 science breakthroughs of 2013.
The cancer research community experienced a sea change in 2013 as a strategy, decades in the making, finally cemented its potential. Promising results emerged from clinical trials of cancer immunotherapy, in which treatments target the body's immune system rather than tumours directly. The new treatments push T cells and other immune cells to combat cancer — and the editors of believe that such approaches are now displaying enough promise to top their list of the year's most important scientific breakthroughs. Though the ultimate impact on the disease is not known, results so far have been highlighting its success.
This annual list of groundbreaking scientific achievements, selected by and its international nonprofit publisher, AAAS, also includes major breakthroughs in solar cell technologies, genome-editing techniques and vaccine design strategies, to name a few.
“This year there was no mistaking the immense promise of cancer immunotherapy,” Tim Appenzeller, chief news editor of the journal saidin a press release by the American Association for the Advancement of Science (AAAS). “So far, this strategy of harnessing the immune system to attack tumours works only for some cancers and a few patients, so it's important not to overstate the immediate benefits. But many cancer specialists are convinced that they are seeing the birth of an important new paradigm for cancer treatment.”
Many of today's advances in cancer immunotherapy revolve around CTLA-4 (cytotoxic T-lymphocyte antigen 4) — a receptor on T cells that was discovered in 1987. “The early steps were taken by French cancer immunologist James Allison, now at the University of Texas, MD Anderson Cancer Center in Houston. CTLA-4 prevented the T cells from attacking invaders with their full force.
In 1996, James Allison showed that blocking CTLA-4 in mice could unleash T cells against tumour cells in the animals that finally “erased tumours in mice.”
In the meantime, Japanese researchers identified another “brake” on T cells known as PD-1. Clinical trials involving this receptor began in 2006, and preliminary results in small groups of patients appear to be promising.
Another area of interest involves genetically modifying T cells to make them target tumours. In 2011, this strategy, which was known as chimeric antigen therapy, or CAR therapy, electrified the cancer research field, and it is now the subject of numerous clinical trials, particularly in blood cancers.
Accordingly, many pharmaceutical companies that wanted nothing to do with immunotherapy several years ago are now investing heavily, the release noted.
There is still plenty of uncertainty regarding how many patients will benefit from these therapies, most of which remain experimental — and for which forms of cancer they will work best, the release noted. Scientists are busy trying to identify biomarkers that might offer answers, and thinking of ways to make treatments more potent. But a new chapter in cancer research and treatment has begun. The journal’s list of nine other groundbreaking scientific achievements from the past year follows.
CRISPR: Akin to the discovery of the microscope in the 1920 that “touched off a revolution in surgical procedures,” the discovery of a bacterial protein — Cas9 — gives “researchers the equivalent of a molecular surgery kit for routinely disabling, activating, or changing genes,” the paper notes.
Though CRISPR, the gene-editing technique was discovered in bacteria, researchers use it as a scalpel for surgery on individual genes. Its popularity soared this year — with over 50 publications in 10 months — as more than a dozen teams of researchers used it to manipulate the genomes of various plant, animal and human cells.
Cloning human embryos: After years of failure, researchers were able to derive stem cells from cloned human embryos this year. Scientists were able to clone sheep, mice, pigs, dogs and other animals, but human cells proved really tricky.
But in 2007, researchers at the Oregon National Primate Research Center in Beaverton succeeded in cloning monkey embryos and extract embryonic stem cells. In the process they realised that caffeine plays an important role in the process, stabilizing key molecules in delicate human egg cells.
CLARITY: This imaging technique, which renders brain tissue transparent by “by removing the fatty, light-scattering lipid molecules that form cellular membranes.” The lipids are replaced with molecules of “clear gel” but all neurons (as well as other brain cells) are left intact and on full display. This has changed the way researchers look at this intricate organ in 2013.
According to the paper, researchers say the “advance could speed up by 100-fold tasks such as counting all the neurons in a given brain region and could make traditional methods of imaging post-mortem brain tissue irrelevant.” Currently, the technique is limited to small amounts of tissue.
Mini-organs: Researchers made remarkable progress growing mini human-like “organoids” in vitro this year. These included liver buds, mini-kidneys and tiny brains. miniaturized human organs may prove to be much better models of human disease than animals.
If it is a challenge to “coax stem cells to grow into specific tissues” prodding pluripotent stem cells to develop into organized structures has been nearly impossible. Not any more. Researchers in spectacular style were able to grow a variety of “organoids” in the lab — liver buds, mini-kidneys, and, most remarkably, rudimentary human brains.
Cosmic rays traced to supernova remnants: Although originally detected 100 years ago, scientists have not been sure where the high-energy particles from outer space known as cosmic rays come from. This year, they finally tied the rays to debris clouds left by supernovae, or exploding stars.
Perovskite solar cells: A new generation of solar-cell materials, cheaper and easier to produce than those in traditional silicon cells, garnered plenty of attention this past year. Perovskite cells are not as efficient as commercial solar cells yet, but they are improving very quickly.
Structural biology guides vaccine design: This year, researchers used the structure of an antibody to design an immunogen — the main ingredient of a vaccine — for a childhood virus that hospitalizes millions each year. It was the first time that structural biology led to such a powerful tool for fighting disease.
Our microbes, our health: Research on the trillions of bacterial cells that call the human body home made it clear how much these microbes do for us. "Personalized" medicine will need to take these microbial tenants into account in order to be effective.
Why we sleep: Studies with mice showed that the brain cleans itself — by expanding channels between neurons and allowing more cerebrospinal fluid to flow through — much more efficiently during sleep. The finding suggests that restoration and repair are among the primary purposes of catching Z's.