By David N. Leff
Editor¿s note: Science Scan is a roundup of recently published biotechnology-relevant research.
Afghanistan is carpeted wall to wall with anti-tank and anti-personnel land mines. So is the militarized border between South Korea and North Korea. In fact, much of the world¿s land surface is studded with these buried high-explosive booby traps.
Military bases and munitions factories throughout the U.S. are inadvertently sown with spilled explosives, mainly TNT, which are comparable to deliberately placed land mines. These chemical contaminants don¿t explode, to maim or kill people or animals, or destroy vehicles. Rather, they are highly toxic to plant life, and human exposure to these harmful compounds can lead to anemia, liver damage and cancer. Hence Superfund hazardous waste cleanups include TNT-fouled areas. But physical remediation doesn¿t come cheap; it involves excavation, reburial, capping with concrete, or incineration. This process produces unusable ash and potential air pollution.
The Swedish chemist, engineer and industrialist Alfred Nobel (1833-1896) invented dynamite, of which TNT ¿ trinitrotoluene ¿ is the prime ingredient. He mixed nitroglycerine with diatomaceous earth, a bulky absorbent mineral consisting of the microscopic skeletal remains of diatoms ¿ aquatic algae-like prehistoric plants. Now a modern plant is being genetically engineered to take up and break down TNT.
This bioremediation demonstration is reported in the December 2001 issue of Nature Biotechnology under the title: ¿Phytodetoxification of TNT by transgenic plants expressing a bacterial nitroreductase.¿ Its authors are microbiologists at the University of Cambridge Institute of Biotechnology in England.
¿There is major international concern,¿ their paper leads off, ¿over the wide-scale contamination of soil and associated groundwater by persistent explosives residues. TNT,¿ it goes on, ¿is one of the most recalcitrant and toxic of all the military explosives.¿
Bacterial bioremediation, despite years of modest commercialization, has not yet really gotten off the ground, so growing plants are on numerous drawing boards as multicellular equivalents of single-cell microbes. ¿Living and competing in soil with toxin-producing bacteria like streptomycetes,¿ an accompanying editorial pointed out, ¿native plants have developed an arsenal of catabolic weapons for degrading organic toxins.¿
The co-authors created transgenic tobacco plants (Nicotiana tabacum) that expressed a TNT-degrading enzyme in their leaf discs. They took the nfsl gene encoding the nitroreductase enzyme from the genome of a pathogenic bacterium, Enterobacter cloacae ¿ an infective species found in sewage, soil and water. They placed seeds from the doctored tobacco plants in liquid medium laced with concentrations of TNT, which is poisonous to normal plants. The seeds germinated, grew and removed all the TNT from solution. In one experiment, wild-type tobacco plants removed 78 percent of TNT in 168 hours, while transgenic plants got rid of 71 percent within the first six hours, and 100 percent in 20 hours.
¿Plants have potentially impressive economic benefits as a robust and renewable resource,¿ their article points out. ¿They have a remarkable ability to extract compounds from the surrounding environment; their root systems are generally extensive, and promote dramatically increased microbial numbers and activity.¿
The Cambridge team hopes next to engineer trees that produce enzymes such as nitroreductase, capable of degrading or sequestering all the major classes of explosives. They note that poplar trees, as deep-rooted, fast-growing perennials, ¿are well suited for affordable, sustainable remediation of heavily contaminated sites.¿
A Protean Protein, Osteopontin, May Offer Therapeutic Target Treating Multiple Sclerosis
Osteopontin, a.k.a. bone sialoprotein, is a multipurpose molecule. Its gene increases expression in the brains of individuals with multiple sclerosis (MS), and in the spinal cords of MS mouse models. Osteopontin is produced by many epithelial cell types. It¿s found in plasma, urine, milk and bile. Mice minus osteopontin were more resistant to MS and its frequent relapses.
A paper in Science dated Nov. 23, 2001, is titled, ¿The influence of the proinflammatory cytokine, osteopontin, on autoimmune demyelinating disease.¿ The journal article concludes: ¿Finally, our data suggest that neurons may also secrete this proinflammatory molecule and participate in the autoimmune process. Potentially, neuronal osteopontin secretion could modulate inflammation and demyelination and could influence the clinical severity of the disease.¿ It proposes that osteopontin ¿may offer a potential target in blocking development of progressive MS.¿
It Takes Shards From Host T Cell As Well As Orts Of Target Antigen To Spark Immune Response
T lymphocytes are the enforcer cells of the immune system. When a T cell perceives and apprehends a foreign, intruding antigen, its killer function has just begun. T cells don¿t fight infections from a particular virus or bacterium until, so to speak, their elbow is jogged to let them know they are needed at action stations. Special antigen-presenting cells of the immune system¿s major histocompatibility complex (MHC) get the T cell¿s attention by exposing it to specific, tiny bits of pathogen.
However, scientists at Stanford University have discovered a paradoxical two-step that complicates this elaborate immunological minuet. To achieve the strongest T-cell response, they report, small pieces of protein completely unrelated to the enemy antigen, but normally gathered from the host itself, must also be carried into the zone of contact ¿ the ¿immunological synapse¿ ¿ between the T cell and the antigen-presenting cell.
A paper in Nature Immunology, published online Dec. 3, 2001, presents this paradox under the title: ¿Costimulation and endogenous MHC ligands contribute to T cell recognition.¿
Illuminating this intricate dance at the interface has revealed that although specificity is the bedrock upon which all of T-cell biology is understood, the system cannot function optimally without contribution from the nonspecific as well.