For more than 40 years, Bisphenol A, more commonly known as BPA, was used in everything from plastic baby bottles and the lining of metal food containers to dental sealants. When scientists began seeing a connection between BPA and abnormal sperm and egg development, it set off worldwide public health concerns. The types of abnormal development researchers detected could lead to increased cases of Downs and Klinefelter syndromes in children or to infertility.As more scientists began investigating the effects of toxicant exposure and links to abnormal fetal development, three University of Georgia researchers discovered a more efficient, accurate and cost-effective way to conduct these studies using cells in a petri dish. Franklin West and Steve Stice, animal scientists in the UGA College of Agricultural and Environmental Sciences, and Mary Alice Smith, a toxicologist in environmental health science in the UGA College of Public Health, began testing the efficiency of a technology West and Stice developed to measure the effects of environmental toxicants. They use cells that come from stem cells and represent the early cells that eventually will form sperm cells in adults. The cells are highly vulnerable to toxicants.Their findings were published recently in Toxicological Sciences.“There is no human system to study toxicant effects on early sperm development,” West said. “But, we can expose these human cells to different toxicants and predict how changes will impact birth defects and fertility later in life.”Currently, most developmental toxicological studies are done using mice or rats. “We need to move away from rodent tests because they often won’t tell us how detrimental or safe chemicals are in humans,” West said. “For example, the potential effects of BPA in humans, especially in the unborn child, is still hotly contested. This cell culture system moves us away from animal testing, which most agree is preferable as long as the studies are equally or more reliable.”The new testing model fills a void left by current methods and provides human-specific results.“Using animal studies, you are looking at more than a year to test a chemical in rodents,” Stice said. “Using this test, we get results in two to three weeks at most and possibly shorter.”Considering the vast number of untested chemicals humans are exposed to, with new ones coming out every day, animal testing will never be practical to prioritize which chemicals need further testing, Stice said. There are more than 80,000 chemicals in the environment that haven’t been tested for human impact mainly because of the cost and time required using current procedures.The reliability of those results also must be considered.“Mice don’t have three or four (of the) critically important genes that are leading causes of infertility,” West explained. “Sperm and egg cells are the only cells that go through meiosis, a special type of cell division necessary for sexual reproduction. You can’t use another type of cell to find the impact a chemical has on these cells and, in turn, fetal development.”West first developed the germ-like cells during his doctoral work in Stice’s UGA laboratory.“Our next step with the cells is to test more chemicals and see what happens with more compounds,” he said.Stice also plans to use neural and bone forming cells he developed to test chemicals for developmental neurological and skeletal toxicology. Scientists at the Environmental Protection Agency already have demonstrated in peer-reviewed studies that these types of cells are very sensitive to known toxins such as lead and mercury. The team is now testing more chemicals on these cells.“If the assay is predictive and repeatable, the chemical industry will have better, faster and less expensive test systems and, as a result, will reduce the use of animal testing and experiments,” Stice said.“Testing more known chemicals for developmental toxicology will validate these assays for later use by the chemical industry. Our shared long-term goal is to ensure the health and well being of our children,” he said.An abstract of the journal article is available at http://toxsci.oxfordjournals.org/content/129/1/9.
May 19, 2008 (CIDRAP News) – Indonesia’s recent announcement that it would immediately begin sharing H5N1 avian influenza genetic sequences with a new public database is being hailed by experts as a promising development, though there is a concern that having actual virus isolates would be better.Indonesia’s decision, announced by Health Minister Siti Fadilah Supari, was detailed in a May 15 report from the Associated Press (AP).In early 2007 Indonesia stopped sharing H5N1 virus samples with the World Health Organization (WHO) to protest what it perceived as a lack of access to costly pandemic vaccines that companies in developed countries produce from the shared samples. The government has shared only a few samples with WHO labs since then.Though Indonesia’s embargo has drawn support from some other developing countries and nongovernmental organizations, the country was widely criticized by global health officials and researchers, who have said sample sharing is crucial for tracking the evolution of the virus and developing treatments and vaccines.”We have always promoted the sharing of influenza data, all we ask for is that it be done in a fair, transparent, and equitable manner,” Supari said of Indonesia’s decision to contribute sequence data to the new database, known as the Global Initiative on Sharing Avian Influenza Data (GISAID), according to the AP report.A WHO working group has met several times to resolve the virus-sharing dispute, but has made little progress. The issue is expected to surface at the annual World Health Assembly, which started today in Geneva. However, the working group’s next formal meeting is scheduled for November.Benefits, limitations of sequence dataTwo researchers who work with H5N1 viruses say they are pleased that Indonesia, which leads the world in human H5N1 cases and deaths, will share the genetic sequences from their virus samples. However, their opinions varied on how useful the genetic sequences will be without the actual H5N1 virus isolates, which are used to make seed strains for vaccines.Richard Webby, PhD, a virologist at St Jude Children’s Research Hospital in Memphis, Tenn., told CIDRAP News that the sequences would allow researchers to track virus evolution.”It is absolutely a step in the right direction, and it allows everyone to see how the Indonesian viruses are evolving genetically,” Webby said. “Unfortunately, however, our ability to accurately predict antigenic and biologic properties from sequence data alone is embarrassingly poor. So, no, it [providing genetic sequence data] is not as good as sharing viruses.”Webby added that the most important aspect scientists can determine from a viral isolate that they can’t learn from a sequence is antigenicity—how well a virus will cross-react with antibodies generated against other strains. “Antigenic relatedness, not genetic relatedness, is key to vaccine strain selection,” he said.Also, sequence data alone can’t predict the transmission and pathogenicity changes that researchers depend on to make risk assessments, Webby said.Adolfo Garcia-Sastre, PhD, a virologist at Mount Sinai School of Medicine in New York City, also welcomed the news about Indonesia sharing its viral sequences and voiced a more optimistic view on their usefulness.”Sequences are very important to understand antigenicity, and even if no viruses are shared, provide the basis to make reagents to experimentally test antigenicity and pathogenicity,” he told CIDRAP News. Garcia-Sastre is also principal investigator for the Center for Research on Influenza Pathogenesis, one of six National Institute for Allergy and Infectious Diseases Centers of Excellence for Influenza Research and Surveillance.GISAID launches data-sharing platformThe idea for the GISAID database was generated by a group of 70 scientists and health officials who signed a letter in the August 31, 2006, issue of Nature proposing the formation of a new consortium to promote greater sharing of H5N1 genetic sequences.Aside from concerns about potential social inequities, virus-sharing has been a flashpoint for other controversies, including intellectual property rights and published credits for virus sources in scientific papers.Supari had earlier signaled Indonesia’s support for the GISAID database when she announced its initial launch in March 2007, according to a Mar 28, 2007, GISAID press release. Her support for the GISAID database followed a technical meeting on the virus-sharing issue that was attended by health ministers of countries that have been hit by the H5N1 virus, GISAID’s statement said.An official with GISAID, who asked not to be named, told CIDRAP News that the database’s platform for sharing H5N1 genetic sequences went live on May 15. The official confirmed that Indonesia has committed to sharing its virus data and is currently uploading its sequences into the GISAID EpiFlu database. China, Russia, and other nations are also in the process of submitting sequences, the GISAID source said.”This global health research community will find that the GISAID platform provides a high standard of data and analysis tools that uniquely promotes responsible sharing of information,” Supari said in the 2007 press release.GISAID said the public can freely access the database, which includes both human and animal H5N1 sequences, after they register and agree to share and credit the use of others’ data, analyze findings jointly, publish results collaboratively, and refrain from pressing intellectual property rights issues that relate to diagnostic, drug, and vaccine developments.When the plan to form GISAID was announced in 2006, one of the global health officials who signed the Nature letter was Dr. Nancy Cox, head of the Influenza Division at the US Centers for Disease Control and Prevention (CDC). Cox had told CIDRAP News that the GISAID database would be very useful because it would be linked with clinical and epidemiological data.The efforts of Peter Bogner, GISAID director, were instrumental in garnering the support of Supari and other officials, the AP reported. Bogner is a former broadcast executive who became involved in virus-sharing issues after attending a World Economic Forum in Switzerland 2 years ago, the report said.See also:Aug 25, 2006, CIDRAP News story “Scientists launch effort to share avian flu data”GISAID Web sitehttp://www.gisaid.org/WHO World Health Assembly agenda and proceedings