More than once last year, researchers described leaps in medical science that were so breathtaking, and held so much potential for patients, that they immediately joined the list of fields to watch in the year ahead. In most cases, the work was, and is, at an early stage and its success far from certain. But some may go down in history for transforming how medicine is done.
Often, medical science surges ahead when different areas converge. That's the case with genome editing, which gives scientists the extraordinary ability to rewrite genes in living organisms. At the heart of the process are enzymes that can sever DNA at chosen locations. But to be useful, it required advances in computational genetics, and exquisite techniques to manipulate biological cells.
Then there is the microbiome, the name given to the community of microbes that live in and on our bodies. The trillions of bacteria that live in our guts, for example, influence our development, our metabolism, and our risk of scores of diseases. The prospect of treating, or preventing disease, through manipulating the microbiome, encouraging bugs here, and fewer there, is a radical departure for medicine that looks entirely realistic.
Cost is one of the greatest barriers to medical progress, so the falling price of genetic sequencing was bound to have an impact. Perhaps its most exciting application is the creation of gene profiles for tumours, which can be used to tailor therapies for individual patients. There is a long way to go, but solid progress has already been made.
Over the next year and more these three tantalising areas may prove their worth, be superseded by better approaches, or fail spectacularly. Whatever the outcome, they are ones to watch.
In 2009, doctors in Germany treated a man for leukaemia and in doing so cured him of HIV. Timothy Ray Brown was given a bone marrow transplant, a common enough option for leukaemia, but his donor was chosen specifically for a rare mutation in their cells. The genetic quirk, carried by a few per cent of the population, made the donor's white blood cells impervious to HIV. Once transplanted, the cells repopulated Brown's immune system, and made him resistant to the virus. He is the only person effectively to be cured of HIV.
The same approach cannot be used for the millions of others with HIV. There are too few appropriate donors, and the transplant operation alone carries a risk of death. But there might be another way, which draws on a technique called genome editing. The process is simple to explain, though complex to perform. First, extract immune cells from the patient. Then use enzymes to rewrite the DNA in those cells so they carry HIV-resistant genes. Finally, infuse the cells back into the patient. With luck, the modified immune cells thrive in the body, while the others die off.
The first clinical trial to do this in HIV patients ends this month. "We don't know if it's going to work, but the potential is amazing," says Chris Mason, professor of regenerative medicine at University College London.
Manipulating stomach bugs
One of the hottest fields to emerge in medicine has shown the uses of microbes in and on our bodies. They are intimately woven into our physiology and play a crucial role in our metabolism, development, as well as our susceptibility and response to diseases.
Last year, the Human Microbiome Project mapped the full community of microbes - the microbiome - that lurk in various parts of the healthy human body. Scientists are now finding that shifts in these bacterial groups raise or lower our risk of a staggeringly broad range of diseases. The reason is simple - the bugs release substances that are active in our bodies.
In the year ahead, scientists expect to make headway in understanding the role of the microbiome in metabolic diseases, such as obesity and type II diabetes, and inflammatory problems, including colitis, Crohn's disease and irritable bowel disorder.
The cost of reading DNA has fallen to the point that doctors can take a biopsy from a tumour and see all of the mutations that triggered and drive the disease in an individual patient. Less than a decade ago, this was the stuff of science fiction.
The genetic histories of tumours that scientists can now piece together are crucial for grasping the basic biology of cancer, but also for efforts to improve cancer therapy. These profiles can tell doctors which drugs will work, and which are likely to cause horrible side-effects.
To this end, the International Cancer Genome Consortium (ICGC) has begun sequencing the genetic code of 50 cancers in multiple patients, from brain and bladder, to lung and liver. For each disease, scientists want to define a genetic signature - the series of genes that mutate to cause the disease.
The first results were released last year but far more are set to follow. "This gives us an unprecedented glimpse at what drives cancer, and tell us which pathways we should be targeting with drugs," says Ultan McDermott at the Wellcome Trust Sanger Institute in Cambridge.