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Take two scorpion pills and call me in the morning

Research at Tel Aviv University suggests that natural compounds found in the venom of scorpions may act as painkillers. Michael Gurevitz, a professor at Tel Aviv University's Department of Plant Sciences, is developing compounds that mimic the toxins of the Israeli yellow scorpion. One effect of scorpion toxin is the targeting and inhibition of sodium channels, some of which are involved in pain reception. Gurevitz suggests that studying this mechanism can lead to the development of efficient painkillers.

Mammals have nine different sodium channels, but only a certain subtype delivers pain to the brain, said Gurevitz in a press release. Researchers may be able to modify the scorpion toxins, thus "making them more potent and specific for certain pain-mediating sodium channels."

Before you think using scorpion poison to treat pain is ludicrous, let Gurevitz remind you that Chinese medicine has used scorpion venom as an analgesic for centuries. Potential applications of dried scorpion powder (quan xie) include headaches, joint pain, and convulsions.

Needless to say, the FDA exists for a reason..

Beer strengthens bones

Scientists at U.C. Davis say that a silicon compound found in beer can help strengthen your bones. Silicon is a key ingredient for increasing bone mineral density, and is present in beer as orthosilicic acid (OSA).

Researchers at the department of food science and technology at U.C. Davis tested 100 commercial beers for their silicon content. The scientists examined the silicon content of barley used in the brewing process—the husk of the barley contains the silicon.

They found that pale colored malts contained higher silicon levels than chocolate and black malts, which have been roasted.

So what beer do I drink to prevent osteoporosis? The U.C. Davis research suggests you should drink light-colored beers to increase you silicon intake. Too bad for us porter lovers.

Advances in Flu Vaccines

All currently licensed flu vaccines in the United States are produced in chicken eggs, manufactured in a process that dates back to World War II. Fertilized eggs are injected with the influenza virus, followed by chemical inactivation, purification, and testing—a process that takes six to nine months and requires millions of chicken eggs. In addition to their protracted development, egg-based vaccines have induced hypersensitivity reactions in egg-allergic recipients and in rare cases caused debilitating disorders (A 1976 swine flu vaccine caused 500 incidences of Guillain-Barré syndrome, a paralyzing autoimmune disorder).

Scientists and public health officials from the NIH, NIAID, and FDA gathered at the NIH campus on Dec. 11 to discuss current flu vaccines and ones being developed. The theme was simple: egg-based vaccine production is slow and outdated but continues to produce safe and effective vaccines while other technologies are being developed. These alternative platforms include DNA vaccines, recombinant subunit vaccines, virus-like particle vaccines, and synthetic peptide vaccines.

To mount an immune response against an influenza virus, antibodies must be produced against a specific antigen on the virus. Two types of antigens used to characterize the influenza virus are hemagglutinin (HA) and neurominidase (NA)—hence flu virus subtypes denoted as H1N1 (“swine” flu) and H5N1 (“avian” flu).

Recombinant subunit vaccines are at the forefront of the vaccine platforms in development. With this method, a virus is used to infect insect cells to produce high amounts of a protein. This protein is then packaged as the vaccine. Carole Heilman, director of the division of microbiology and infectious disease at the NIAID, explained the protocol and why it is the most promising in new vaccine technologies: one is able to immediately identify the gene of the surface protein one wants to elicit an immune response against, transfect the DNA into a baculovirus, infect insect cells in 48 to 72 hours, and obtain a yield of approximately 90% of usable protein for use as the vaccine.

Heilman noted that the baculovirus expression system is one of the most advanced new technologies, with one five-hundred liter fermentor having the equivalent production capacity of 50,000 eggs. Protein Sciences, a pharmaceutical company using the baculovirus technology, has an influenza vaccine candidate in Phase III named FluBlok.

Research into influenza structure and immunity will provide opportunities to develop vaccines quicker and even preemptively, something that will prove necessary as forms of influenza continue to evolve and mutate almost daily. Not only will vaccine improvement support a more rapid and flexible response to influenza outbreaks, the technologies developed will also apply to prophylaxis against diseases like malaria, HIV, and tuberculosis.

Eat your greens

Soon parents will have another reason to make their kids eat their greens. Geneticists are engineering plants like lettuce and tobacco to produce vaccines for diseases like malaria, anthrax and E. coli poisoning.

Henry Daniell, a researcher at the University of Central Florida, has been using transgenic plants as protein factories for years. Using a technique called microprojectile bombardment, Daniell coats tiny microparticles of gold with his vectors—short strands of DNA containing the toxin genes—and shoots them at high velocities and under highly pressurized helium at lettuce or tobacco leaves. Leaves are then cut and placed on a plant regeneration medium and after sequencing to confirm the presence of the toxin genes, the transgenic plants are selected and grown.

By inserting the genes for toxins of common diseases into the chloroplast genome, Daniell has engineered plants to function as bioreactors, pumping out loads of protective proteins he can package as vaccines. A vaccine containing a suitable dose of toxin, for say, E. coli poisoning, would stimulate the immune system to produce antibodies against it and grant the patient immunity.

In 2005, Daniell created an anthrax vaccine that protected 100% of immunized mice from anthrax toxin, for 300 days. He theorized that in humans this would confer immunity for around 50 years. He also isolated 150 milligrams of the protective protein from each plant, meaning a scale-up would produce an astonishing 360 million doses of vaccine from 1 acre of land. As compared to mammalian cell culture systems, genetically-modified plants would be capable of producing engineered proteins in much larger quantities.

Combating diseases in impoverished nations is one of the clear implications of these plant-derived vaccines. One can imagine a scenario where a country like Bangladesh could plant, harvest and purify cholera vaccine-producing plants on-site. Daniell is currently working on a dual-purpose vaccine for cholera and malaria.

Proponents point out that engineered proteins produced in plants are free of bacterial contaminants and human pathogens, a considerable problem with mammalian cell cultures. However, large-scale protein purification methods are costly and production methods would need to be developed for clinical applications—clinical-grade pharmaceutical production requires fully-characterized and contaminant-free materials.

A study published today in the Proceedings of the National Academy of Sciences (PNAS) used tobacco leaves to make antibodies to the West Nile virus. Arizona State University researchers showed the antibodies worked just as well as those derived from mammalian cell culture, protecting mice from the virus even days after infection.

Harnessing plant cells or bacteria as biofactories for protein production—for vaccines or biofuels—is an encouraging ambition of biomedical research. The promise of engineering organisms to synthesize exactly what we need, or perform exactly what we want, is the core of synthetic biology.

A needle in a haystack

When Craig Venter started the race to map the human genome, the cost of sequencing a single DNA base was $10. The price has now dropped to lower than 10 cents per base, with technology rapidly being developed to drive the cost of sequencing an entire genome to $5,000. (Illumina’s HiSeq 2000 sequencer can sequence a human genome 30 times over for around $10,000—with an initial investment of $700,000).

With sequencing costs plummeting, it is cheaper than ever to research the genetic basis of disease. In fact, determining the genetic variation indicative of disease is arguably the most important field of biomedical research today, and will be for decades to come.

The efforts by scientists to find these genetic variants in select populations are called genome-wide association studies (GWAS). Such studies may compare the genomes of children with leukemia to those of healthy children to track minute differences in their DNA. (A new three year, $65 million study launched by St. Jude’s in Memphis and Washington University in St. Louis will scour the genomes of 600 patients for genetic variations in childhood cancers.) Researchers can determine which genetic mutations are present in a diseased individual, but establishing what causes the disease remains much more complicated.

Genome-wide association studies find single base mutations called single nucleotide polymorphisms (or SNPs, pronounced “snips”). By running patient samples on microarrays—DNA chips containing hundreds of thousands of immobilized SNPs—genetic similarities among diseased populations can be cataloged. Although more than one million SNPs have been identified in the human genome (and $76 million of the 2009 NIH budget went to GWAS and gene expression studies), scientists are increasingly pointing out how little we have inferred from SNPs.

A review published in Bioinformatics on Jan. 6 argued that current association studies often consider one SNP at a time, ignoring their genomic and environmental context. A Duke study, highlighted yesterday in the New York Times, showed that many SNPs may be incorrectly implicated by GWAS, and thus useless in identifying genes that cause disease.

Determining the genetic basis of disease may turn out to be harder than finding a needle in the haystack. Or a SNP in a genome.