A more sensitive SARS diagnostic test than currently exists has been developed by Mailman researchers Ian Lipkin and Thomas Briese and hand-delivered to Chinese researchers during a short visit by the two to Beijing. The researchers, invited by the Chinese government, demonstrated the test on May 5 during a SARS symposium convened by the Ministry of Health and the Ministry of Science and Technology. By the same evening, Chinese scientists were running clinical samples through the assay, which can detect the virus in under two hours.
"The test still needs to be validated in China," says Dr. Lipkin, professor of epidemiology. "Researchers there are now field-testing the assay to see how early it detects SARS in an infected person and how many false negatives it gives. They need to find out when people are infectious so they can determine who to quarantine."
The diagnostic test Drs. Lipkin and Briese developed uses real-time PCR (polymerase chain reaction) to amplify a piece of RNA unique to the SARS coronavirus. During the assay, dye is detected if the SARS RNA is copied. The amount of dye detected also indicates how much virus is present in the sample. This may be important in following response to therapy or assessing infectivity.
The assay differs from other current PCR-based SARS diagnostics by detecting a gene present in multiple copies instead of just one. That strategy produces an assay that detects lower concentrations of SARS in blood, throat, and fecal samples. Columbia submitted a patent application on April 17.
"Our goal is to rapidly release this assay where it can be most useful," Dr. Lipkin says. "Columbia's Science and Technology Ventures recognizes the gravity of SARS and has been generous in giving us leave to provide the assay without charge to scientists on the front lines in China."
As the leader of the Northeast Biodefense Center, Dr. Lipkin has also invited several Chinese scientists to universities and laboratories affiliated with the center to collaborate with U.S. researchers. The Chinese scientists "represent the very best of the extraordinary talent in that country," Dr. Lipkin says, and will work on diagnostic tools, pathogenesis, drug development and vaccines. Dr. Lipkin adds that U.S. ambassador to China Clark T. Randt and his staff at the U.S. Embassy in Beijing applaud this effort and have worked tirelessly to ensure that visas are processed expeditiously so that this program can go forward.
At press time, Drs. Scott Hammer, chief of Infectious Disease, Lipkin and Allan Rosenfield, dean of the Mailman School of Public Health, were planning to convene an international meeting on SARS May 17 with New York Academy of Sciences.
In other developments, Gerald Fischbach, executive vice president and dean, Dr. Rosenfield, and Columbia University president Lee Bollinger, will attend a dinner at the Chinese consulate June 2 to establish additional ties between Columbia and China in biomedical research, as well as other fields.
Dr. Lipkin says he was struck by the effect SARS is having on everyday life in China. "It was eerie walking around Beijing. The people wear masks, the city is deserted, and there's no traffic. You sense how badly they're hurting economically. They're confronted with an enormous problem."
In a study of former nuclear weapons workers in Russia, Columbia University Health Sciences researchers and colleagues in Russia have found that those exposed to high levels of plutonium may sustain far more genetic damage than previously believed, yet remain healthy.
Significantly, the researchers also determined that the degree of chromosomal damage can be used as a marker to enable better estimation of how much radiation a person has received. Such a marker could increase the power of epidemiological studies of exposure to radon a radioactive gas found in homes and neutron radiation, encountered by frequent flyers and airline personnel during flights, says Dr. David J. Brenner, professor of radiation oncology at P&S and of environmental health science at the Mailman School of Public Health.
Dr. Brenner, senior author of the study, and fellow researchers, used a new technique that allows detection of large-scale DNA damage within individual chromosomes. The technique, called mBAND, paints colored bands along the length of an individual chromosome. Analogous to bar-coding, a change in the color band order implies that rearrangement of genetic material has occurred in the chromosome. Damage involving more than one chromosome such as when a piece from one chromosome breaks off and joins a different chromosome is less common though more easily detectable.
The investigators examined blood samples from 31 individuals, 26 of whom were exposed to radiation, including plutonium, gamma rays, and other chemical mutagens, during their work at the Mayak Production Association, a nuclear weapons production plant near the city of Ozyorsk in central Russia. Exposures took place over 20 or more years starting between 1949 and 1989. The other five people worked at the plant but were not exposed; they served as a control group. For the 11 people who had contact with high levels of plutonium, more than half their blood cells contained large-scale damage to individual chromosomes. The other workers had little such damage. The findings appear in the May issue of the American Journal of Human Genetics.
Until recently, not much was known about the genetics of hair generation and loss. But now P&S researchers have identified a gene that codes for an adhesion protein integral to hair growth. The findings might lead to better, longer-lasting hair-removal treatments.
In a study led by Dr. Angela Christiano, associate professor of dermatology and genetics & development at P&S, Columbia researchers and colleagues at other universities discovered a protein, desmoglein 4 (DSG4), that holds cells together and ensures they are in the correct place during hair shaft formation. In this way, the cells receive the right instructions to become a particular type of hair cell.
The researchers determined the protein's function by identifying mutations in human families with a rare inherited hair disorder, called hypotrichosis, and in mice. People with mutated forms of the gene and mice lacking the gene have thin, sparse hair that is fragile and breaks easily.
"Without DSG4, the cells separate from each other and become disorganized," Dr. Christiano says. "Rather than the six ordered layers of a normal hair fiber, you get a cluster of misdirected cells in the hair follicle."
The DSG4 gene is the third found in Dr. Christiano's laboratory to have a role in human hair growth. It codes for a structural protein while the other two are regulatory genes that turn other genes on and off. All three genes could have roles in gene therapy designed for hair removal both permanent and temporary Dr. Christiano says. Such treatments would involve rubbing lotions or gels into the skin to inhibit hair growth. The findings were published in the April 18 issue of Cell.
A start-up company, Skinetics Bioscience LLC, is forming to develop hair-growth and hair-removal products and to conduct clinical trials based on the findings from Dr. Christiano's laboratory.