Science Editor

Editor's note: Science Scan is a roundup of recently published biotechnology-relevant research.

Besides failing vision, motor coordination and memory, another salient toll of aging is hearing loss. Throughout the superannuating population, much of this diminished hearing ability is due to environmental insults to the ears - such as sustained, loud noise levels. Another factor is the genes we inherit.

The commonest cause of hearing loss occurs through damage to the sensory hair cells that grow within the organ of Corti - the auditory sensory epithelium in mammalian inner ears. A 19th-century Italian anatomist, Marquis Alonso Corti (1822-1888), gave his name to this spiral auditory organ. Its cells are essential for perception of sound, and when lost they do not regenerate.

In the May 2003 issue of Nature Cell Biology, researchers at the House Ear Institute (affiliated with the University of California at Los Angeles) identify one key gene that seems to be closely linked to progressive hearing loss in mutant knockout mice. Their article bears the title "Progressive hearing loss in mice lacking the cyclin-dependent kinase inhibitor Ink4d."

Two types of cells in the organ of Corti are important for sound perception: hair cells and supporting cells. The former have become specialized in the detection of sound waves, which are transmitted through liquid in the auditory canals. As these sensory hair cells move and bend in the fluid, their movement is translated into a nerve impulse that is forwarded to the brain. During embryogenesis, these cells divide constantly - a process that continues until just after birth.

In their paper, the co-authors demonstrated that a mouse gene called Ink4d is involved in this developmental process. Deletion of Ink4d allows the sensory hair cells to divide again within the adult ear. However, this is not good news for the mice or their hearing. The dividing cells undergo apoptosis, the programmed cell death that seems to cause the hearing loss. Although Ink4d is a good candidate gene for inherited hearing failure, it remains unclear whether it is mutated in human patients who are losing their ability to hear.

Ink4d is known to inhibit important regulators of cell division and also has roles in stopping other cell types from dividing. The newly published results imply that removing inhibitors of cell division can lead to progressive hearing loss in mice. As the easiest way to reverse human hearing loss might involve the generation of new sensory hair cells by encouraging the cells to divide, this work has important implications for the treatment of human deafness, as "appropriate for gene therapy targets to replace lost hair cells," the paper concludes.

Mosquitos That Air-Freight West Nile Virus Plus Malarial Parasites Confront Ace-1 Gene Of Doom

Despite some fears, West Nile virus has not emerged as a weapon of mass destruction. But the mosquito-borne infection has to be reckoned with on its own infectious merits. A pointed reckoning has been undertaken by French molecular evolutionists at the University of Montpellier. Their one-page report in Nature dated May 8, 2003, is titled "Insecticide resistance in mosquito vectors."

Most of the insecticides currently employed against mosquitos rely on the enzyme acetylcholinesterase. A single DNA molecular change in the genetic code might be responsible for the past 25 years of insecticide resistance in "Africa, America and Europe" in mosquitos that carry the West Nile virus or the malaria parasite. The finding reported by the Nature "Brief Communication" might help with the design of new insecticide molecules, its authors write.

They found the mutation in 10 highly resistant strains of the West Nile-toting Culex pipiens mosquito from tropical and temperate regions. They also detected the same DNA base substitution in one enzyme-resistant African strain of Anopheles gambiae, the winged single-purpose insect that delivers the malaria parasite.

The mutation in the enzyme, they report, lies in a gene called ace-1. This encodes acetylcholinesterase, the key insecticidal enzyme. As a result, the enzyme loses sensitivity to organophosphates and carbamates, which are widely used in some parts of the world as the active ingredient in insecticides.

"The discovery of the ace-1 mutation that is responsible for insecticide resistance in mosquitos," their paper concludes, "opens the way to new strategies for pest management. The development of new insecticides that can specifically inhibit the G1195 mutant form of acetylcholinesterase will be crucial in overcoming the spread of resistance."

Novel ELISPOT T-Cell Diagnostic Outscored Age- Old Skin-Test Detection Of Tuberculosis Subjects

A large tuberculosis (TB) outbreak in a British school resulted from one full-blown infectious index case. It led to testing 535 students for TB infection with two competing diagnostics - one, the conventional tuberculin skin test, the other a more rapid but unconfirmed ELISPOT detection method. The Lancet, dated April 5, 2003, reported the outcome in an article titled "Comparison of T cell-based assay with tuberculin skin test [TST] for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak."

The study showed that the ELISPOT blood test, developed at the University of Oxford, is more effective than the century-old skin-prick test for diagnosing TB infection. It enables doctors to screen people who have been in contact with an infectious TB sufferer and reliably identify those who are infected long before they actually develop the disease.

"The ELISPOT works in a unique way," the authors explain. "Whereas conventional diagnostic tests rely on detecting antibodies induced by an infection, such antibodies are not generated by TB infection, which is why there has been no blood test until now. TB infection induces a strong response by immune cells in the blood. It is these T cells that the ELISPOT blood test detects."

The Lancet paper signed off by making the following points: "ELISPOT gives quantitative results the morning after taking a blood sample, and is more convenient, objective and rapid than the TST. Introduction of ELISPOT might initially increase the cost of TB control, but the savings that would follow from improved diagnosis of latent TB infection could make it very cost effective in the long term. Fewer false-positive results in uninfected contacts would avoid the costs associated with unnecessary chemoprophylaxis and its associated toxic effects."