Health & Medicine

On November 27, 2005, a team of French surgeons led by Jean-Michel Dubernard of the Édouard Herriot Hospital in Lyon successfully performed the world's first partial face transplant. The patient was Isabelle Dinoire, a 38-year-old Frenchwoman who had been so severely disfigured when her dog scratched and chewed off her face six months earlier that normal surgical repair was impossible. The procedure, which involved attaching the nose, chin, cheeks, and lips of a 46-year-old brain-dead woman, set off a firestorm of criticism that lingered even after the French surgeons declared in July 2006, in the medical journal The Lancet, that the graft was "successful with respect to appearance, sensitivity, and acceptance by the patient."

Clinicians and researchers have raised ethical questions about the transplant, as well as concerns about whether Dinoire was stable enough to give informed consent for the procedure—which dips into uncharted issues involving the relationship between the face and personal identity—and for the regimen of immunosuppressive drugs she must now take for the rest of her life. However, regenerative medicine expert Patrick Warnke of the University of Kiel in Germany (who was not part of the transplant team) points out that "there was no quality of life for the patient without major parts of her face. After the procedure she seemed to feel much better. She was involved in the decision about the means of her reconstruction, according to my information. If she can compete with the restraints of lifelong immunosuppression, then we must respect this somehow."

Kathy A. Svitil

Medical researchers launched a new assault on AIDS in 2006, announcing that three new categories of anti-HIV drugs are in the pipeline. Whereas most previous HIV drugs block enzymes the virus uses to copy itself, the new ones take aim at different stages in the virus's life cycle (the virus is colored green in the micrograph below). Drugs known as entry inhibitors (Pfizer's maraviroc and Schering-Plough's vicriviroc) stop the virus from entering healthy cells by binding to receptors on the cells' surfaces. Integrase inhibitors (Merck's MK-0518 and Gilead Sciences' GS 9137) prevent viral DNA from incorporating itself into the human cell's chromosomes. Finally, maturation inhibitors (Panacos Pharmaceuticals' bevirimat) prevent one of HIV's key structural proteins from forming. All could reach the market by 2009. "Every time we can find a new mechanism to inhibit the virus, it gives us a big advantage," says Bruce Walker, director of the Partners AIDS Research Center at Massachusetts General Hospital and a professor at Harvard Medical School. "Considering that 20 years ago we had nothing, it's an amazing accomplishment."

Susan Karlin

In March the British clinical trials company Parexel gave an experimental drug called TGN1412 to eight patients. TGN1412, a monoclonal antibody developed by TeGenero of Germany, was intended to treat leukemia and autoimmune diseases like arthritis. Instead, six of the test subjects wound up with massive organ failure; the only two unaffected were those who received a placebo.

Tests in mice and nonhuman primates had shown TGN1412 to be safe, but when it was injected into humans—in a dose less than 1/500 of what was given to monkeys—it caused a massive release of infection-fighting T cells that overstimulated the patients' immune systems, resulting in multiple organ failure. The discrepancy in effect may result from a subtle difference between animal and human immune systems, says immunologist James Riley of the University of Pennsylvania. In mice, TGN1412 primarily triggered regulatory T cells, which block the action of other T cells (and thereby reduce autoimmune reactions, wherein immune cells turn on the body's own cells). In humans, however, the drug seemed to activate regular T cells, sparking the immune-system meltdown. Riley believes that the design of this particular trial was inadequate. "Clinical trial designs that test such novel and potentially dangerous biologic therapies should only treat one patient at a time, followed by a reasonable period of time so that adverse events can be monitored," he says.

Regulatory agencies in Europe and the United States are reviewing how to use this new information to improve safety in future drug trials. The British equivalent of the F.D.A. investigated but found "no critical or major deficiencies" in the manufacture and handling of TGN1412, or in the testing and handling of the subjects. The agency did, however, find that the company had inadequate procedures for dealing with emergencies. TeGenero filed for bankruptcy in July. Meanwhile, the six subjects continue to suffer from severely damaged immune systems, and they are likely to be more vulnerable to disease for the rest of their lives.

Nicholas Bakalar

Injecting neurons derived from human embryonic stem cells into rats suffering from Parkinson's-like symptoms allowed the animals to regain movement, according to a study led by neurologist Steven Goldman of the University of Rochester Medical Center. The downside is that the transplanted cells also fostered the growth of benign brain tumors.

Goldman's work builds on previous studies that explored the developmental cues involved in directing an embryonic stem cell to become a functioning neuron. He improved the technique by culturing the stem cells with astrocytes, cells that guide the maturing neurons, that he had taken from the dopamine-producing region of the rat brain. Up to 80 percent of the stem cells cultivated this way then began functioning like dopamine-producing neurons, Goldman reported in November in the journal Nature Medicine. When injected into rats with an artificially induced form of Parkinson's, the cells worked, as demonstrated by the animals' renewed ability to move.

The benign tumors—masses of dividing cells—that formed around each injection site may have been caused by immature precursor cells, neural cells that did not transform into neurons but that retained the ability to divide. Selecting for injection only the neural cells that are destined to become neurons will be the key to success, Goldman says.

Kathleen McGowan