NEWS p5 Abstinence all p7 Vietnam’s winner: p10 Acid test: Many the way: New US Menno de Jong fights with painful cluster family planning chief for local scientists’ headaches are self slams premarital sex. rights. medicating with LSD. Biomarkers trump behavior in mental illness diagnosis Here’s how doctors decide which mental or illness can be drastically different, so pinning scientists are examining panels or ‘pathways’ neurological disorder their troubled patients down the diagnosis is crucial. of biomarkers. Even within the umbrella of a suffer from: they ask questions like, “Are you Scientists are increasingly turning to single disease as defined clinically, there may be hearing voices?” and “Do you feel like people are biomarkers—such as genes or proteins in tissues, several subtypes that could be distinguished at a out to get you?” blood and body fluids—to distinguish between molecular level. Not all that different from how they used to do symptomatically indistinct illnesses. For example, “It’s very unlikely that a it about 100 years ago. “This is the holy grail of research,” says Karoly schizophrenic from one end of the spectrum New techniques are set to radically change that Mirnics, associate professor of medical psychiatry to a schizophrenic on the other end of the approach—and perhaps define new categories at Vanderbilt University. Using techniques that spectrum will show the exact same biomarkers,” within each disease—relying more on changes have only become available in the past few years, says Mirnics. in physiology than in behavior. scientists are looking at the brain, serum and In a study published in August, Bahn’s group “Now we’re at the opposite end of the spinal fluid and asking which combinations of also found that treating schizophrenics who spectrum where we can take an unbiased look,” genes or proteins might be expressed differently had had only one psychotic episode—but not says Stephen Glatt, a psychiatric geneticist at the in these disorders. more than one—corrected abnormal patterns State University of New York in Syracuse. The field is still far from ready for the clinic, in the expression of some metabolites, including Delusions, hallucinations, disorganized but holds great promise: markers could allow glucose, lactate and acetate (PLoS Med. 3, thinking and other psychotic symptoms can for earlier treatment and a better prognosis, e327), underscoring the importance of early result from schizophrenia, Alzheimer disease, ultimately enabling scientists to intervene even intervention. bipolar disorder, manic depression or dementia. before the full-blown disease strikes. Biomarkers are also revealing unexpected Even diabetes and syphilis can induce forms of In one study published in November, insights into the biology of diseases. For psychosis. researchers tested spinal fluid from patients at example, using gene chips, one team found The answers to doctors’ questions can help the first onset of schizophrenia. They found that some pathways involved in energy and whittle down the categories somewhat, but it’s higher levels of a small protein derived from the metabolism are affected in individuals with far from a perfect science. Less than a third of protein VGF, known to be important for energy schizophrenia—which is consistent with individuals with these disorders respond to metabolism, and lower levels of the protein Bahn’s finding (Proc. Natl. Acad. Sci. USA 102, medications, most likely because they are being transthyretin compared with healthy controls. 15533–15538; 2005). The role of metabolism, treated for the wrong one. The treatment for each Post-mortem tissues of schizophrenic brains says Glatt, lead researcher of that study, “could showed that same trend be something that we are not yet even thinking (PLoS Med. 3, e428). about.” Samples from individuals There are important caveats, however. with Alzheimer disease Genetics could account for 50% or fewer of and obsessive-compulsive schizophrenia cases, for instance. Shifts in the disorder did not show those expression of proteins that respond to external differences, but those from variables may be a more reliable predictor in individuals with depression those cases. did. Many of the techniques also lack the sensitivity “This is not really necessary to detect minute traces of molecules. surprising because people Scientists will also need to monitor individuals who have a family history over time, correcting for confounding factors of schizophrenia are also such as the effects of previous treatment, much, much more likely to nutrition and smoking as well as drug and grow up with depression alcohol abuse. or other forms of mental The most challenging aspect might yet turn illness,” says Sabine Bahn, out to be redefining a 100-year-old classification Brain teasers: Doctors director of the Cambridge system. “That will be a major upheaval,” Bahn struggle to distinguish Centre for Neuropsychiatric says. “There may be problems in implementing mental illnesses based Research. them because it would change our entire way of on symptoms alone. To drill down to trends thinking.” unique to a single disease, Amanda Leigh Haag, Denver NATURE MEDICINE VOLUME 12 | NUMBER 1 | JANUARY 2006 3 NEWS Alternative medicine loses its champion Granting credibility to studies on alternative complementary and alternative medicine—acupuncture, chelation therapy and medicine research enterprise that the like—is hard enough at the best of times. The is the model for the world,” he said US National Institutes of Health (NIH) is about in an emailed comment. to find out how much tougher it can get with the The center’s budget has grown from loss of Stephen Straus, who has for seven years $50 million in 1999 to nearly $123 million in overseen that research. 2006. Including projects with other institutes, Citing health reasons, Straus in November alternative medicine research in 2004 accounted announced his resignation as director of the for $305 million in NIH funds. NIH’s National Center for Complementary and Straus has also garnered plaudits as a bridge- Alternative Medicine. He is to take on a role as builder between alternative therapists and senior adviser to NIH director Elias Zerhouni. mainstream biomedical scientists. The NIH has set up a committee to find a “There was great distrust in both communities replacement, but filling Straus’ shoes won’t be at the beginning of the adventure,” says easy. He achieved what few thought possible when Massachusetts General Hospital researcher Bruce he took the job in 1999: a modicum of respect Rosen, who has a grant to study the effects of for the center from scientists who normally have acupuncture on the brain using neuroimaging. Fringe loss: Stephen Straus (inset) has resigned as director of the US National Center for little patience for alternative remedies. “It’s clear [Straus] was really able to pull them Complementary and Alternative Medicine. Even Harold Varmus, who was the NIH together.” director in 1999, initially opposed the center’s Nonetheless, many scientists continue to view “misinformed.” He noted that nearly two-thirds creation. But when Congress ignored him and the center as conferring money and respectability of Americans report using alternative therapies. elevated the NIH’s Office of Alternative Medicine, on nostrums that deserve neither. In July Arthur “The public is using [these] without proof of created in 1992, from second-tier status to a Grollman, a clinical pharmacologist at the State efficacy or safety, which is the very reason that center with all the powers and prerogatives of University of New York at Stony Brook, and a [this] research is so important.” other NIH institutes, Varmus hired Straus, a colleague published a commentary chastising Grollman is unconvinced. The center virologist and immunologist, to lead the center. the center for funding proposals “of dubious spends millions of dollars on clinical trials of “Steve has a high degree of scientific acumen merit,” and calling for an Institute of Medicine questionable alternative remedies such as shark and he brought real science to the conduct of the committee to evaluate its charter and research cartilage, he says. “We do not believe this is center,” Varmus says. portfolio (Science 313, 301–304). justified when at the same time they are funding Straus doesn’t shy away from that Writing in the same issue of Science, Straus NIH grants at distressingly low levels.” characterization. “We and NIH built a shot back that many criticisms of his institute are Meredith Wadman, Washington DC Europe’s sweeping chemical law puts medicines in peril The European Union is set to require extensive need to be registered within 18 months of the whether all the chemicals we use will still testing of nearly every chemical used in regulation's enactment. be on the market,” says Michael Laub, a manufacturing. The rules could bring many The reporting requirements and high communications officer at Denmark-based medicines on the market up for reapproval, but registration costs may force manufacturers to NovoNordisk. few companies are prepared to deal with the withdraw their chemicals from the market, says Though drugs exported to Europe fallout. Dirk Frenzel, a spokesman for the Germany- won't need to be registered, approximately Known as REACH—the framework for the based drugmaker Bayer. 80% of ingredients in US-made drugs are Registration, Evaluation and Authorization Pharmaceutical companies will then have imported—many from Europe. Drug makers of Chemicals—the rules require companies to to find new suppliers, or substitute chemicals in the US appear less prepared than their provide safety and handling information on for those taken off the market. Any new European counterparts. every chemical they make. That information is formulations will need to be resubmitted for “We haven't really thought about this,” not available for more than 90% of chemicals approval, which could take months. says Mark Grayson, a spokesman for the used. “There will be bumps,” says Guy Villax, chief Pharmaceutical Manufacturers of America, Although the regulations, which go into executive officer of Hovione, a Portugal-based the industry's trade organization.