Science Editor

As the year ends, so the roundups begin: Science published its annual Breakthrough of the Year issue on Dec. 18, 2009, and as usual, biomedical research has delivered several of the year's biggest scientific advances.

In some ways, 2009 has been a tough year for research. What is becoming known as the Great Recession has buffeted universities as well as companies over the past year; Science quotes freshly minted Nobelist Elizabeth Blackburn of the University of California at San Francisco as joking to reporters "win a Nobel, get a pay cut," after she, like other faculty, received a pay cut in the form of an unpaid furlough.

But as Science noted, stimulus funds from the American Recovery and Reinvestment Act have also allowed individual scientists to prosper, and provided the fuel for exciting new advances. (See BioWorld Today, Nov. 18, 2009.)

From a biotech perspective, the biggest of the advances that Science has called out is the resurgence of gene therapy treatments, which have had several resounding successes this year. In separate trials, scientists have successfully treated the vision defect Leber congenital amaurosis, the myelination disorder X-linked adenoleukodystrophy, or ALD, and the immune defect adenosine deaminase deficiency-related severe combined immunodeficiency, or ADA-SCID. (See BioWorld Today, Aug. 13, 2009, and Nov. 6, 2009.)

The biggest scientific surprise of the three was the Leber congenital amaurosis trial, which showed that patients continued to improve their visual abilities more than a year after the initial treatment. Such long-term improvement "really goes against established dogma," which says that visual input is necessary during a so-called critical period early in development to establish the ability to interpret the signals that the eyes send to the brain, one of the authors said.

Three patients had originally been treated in 2007, and shown varying but in all cases useful improvement in visual function. (See BioWorld Today, April 29, 2008.)

But during long-term follow-up testing, in the fall, the researchers realized that at least one patient was continuing to improve, even though her visual tests no longer revealed her improvements. At a 12-month follow-up appointment, one patient made "this offhand comment that she's now able to see the digital clock in her father's car" despite the fact that standard visual tests were showing no further improvements in her visual abilities, William Hauswirth told BioWorld Today when the follow-up was published.

The reason for the delay is that it is not due to changes in the eye, but changes in the wiring of the brain. "You don't really see with your eyes - you see with your brain," Hauswirth explained. And the brain changed in its ability to respond to the new input long after the gene therapy.

The successful treatment of two boys for X-linked ALD - a genetic disorder that leaves its victims unable to maintain their myelin sheath, ultimately destroying high-speed neural communication - also was greeted with considerable excitement when it was reported in November. An editorial accompanying the report's publication called it "a comeback for gene therapy" after earlier setbacks had relegated the approach to, though not the trash can, certainly the waiting room.

Senior author Patrick Aubourg stressed that the two boys had not been cured, since gene therapy halts but does not reverse the course of the disease.

But, as lead author Nathalie Cartier said in an interview with the Stop ALD Foundation when the results of the trial were published in November, at this point, several years after the original gene therapy, "the disease is completely stabilized and the boys are fine. They probably will keep some small consequences of their cerebral ALD. But they have normal social lives, normal family lives, they go to school; they are perfectly fine. And there is no reason why this should change with the long-term outcome."

And in a long-term follow-up of a gene therapy trial to treat ADA-SCID, Italian scientists reported that of the 10 boys they had treated, eight no longer required enzyme replacement therapy.

Four years after the replacement gene was first delivered, no serious side effects have been reported - a sharp contrast to an earlier trial that used gene therapy to treat X-linked severe combined immunodeficiency syndrome, which was successful in treating the disease but also caused leukemia in several of those treated.

Science magazine also lists no fewer than three biotech advances in its "areas to watch" - induced pluripotent stem or cells or iPSC's, which were also named by Nature Methods as the method of the year, exome sequencing, and the concept of cancer as a disease that has a significant metabolic component. (See BioWorld Today, Oct. 5, 2009, Aug. 20, 2009, and Nov. 24, 2009.)