Abstract
Industry Wire
Gauging the Economic Impact of the Human Genome Project
The Battelle Memorial Institute has issued a report concerning the economic impact of the Human Genome Project.1 The nonprofit research group indicated that the return on the $3.8 billion the U.S. government invested in the project between 1988 and 2003 totaled $796 billion. The report also indicated that the project has created some 310,000 jobs (as of 2010), generating $244 billion in total personal income. In 2010 alone, the project and associated genomics research and industry activity generated $67 billion in economic output, supported jobs that produced $20 billion in personal income, and provided $3.7 billion in federal taxes—almost paying back the government's total investment in the project in a single year. In addition, Battelle noted that the project had launched a “genomic revolution” that would “create significantly more jobs in the future.”
The report also noted that the project led to significant breakthroughs including new forms of personalized medicine and genetics therapy, greater productivity in agriculture, and potential sources of renewable energy.
The report reached four main conclusions: 1. The economic and functional impacts generated by the project are already “large and widespread.” As discussed above, the project generated a total economic output of $796 billion between 1988 and 2010, generating 310,000 jobs (and 3.8 million job-years of employment) and $244 billion in personal income (or $63,700 per job-year). 2. The federal government invested $3.8 billion in the Human Genome Project from 1990 to 2003, which corresponds to $5.6 billion in 2010 dollars, and provided a return on investment of 141 to 1. 3. The impacts of the project are just beginning. The report noted that “large scale benefits in human medicine and many other diverse applications are still in their early stages,” stating that “[t]he best is truly yet to come.” 4. The project is “arguably the single most influential investment to have been made in modern science and a foundation for progress in the biological sciences moving forward.”
According to the report, the total effort to decode the human genome involved many public and private players over many more years, and the work of entities such as Celera Genomics played an important part, and Battelle's analysis of the functional impacts of the Human Genome Project necessarily included all these contributions. (sk)
References
1. Battelle Technology Partnership Practice. (2011). Economic impact of the Human Genome Project. Available at
Regulatory Wire
European Court to Rule on Patentability of Stem Cells
The European Court of Justice (ECJ) is poised to make a decision regarding the patent eligibility of human embryonic stem cells (hESCs) in Europe. The case began in 2004, when Greenpeace sued in German federal court over a German patent to the University of Bonn involving methods for deriving neural cells from hESCs.1 Although German laws regarding stem cell research have been characterized as the “most restrictive in Europe,” such research is permitted provided that it is performed with pluripotent (rather than totipotent) cells, using cell lines imported from abroad and only cell lines that were made before May 2007. Nevertheless, Greenpeace argued that claims to methods for using hESCs were “immoral and against public order.”
The German federal court ruled for Greenpeace in 2006, and the university appealed to the German Supreme Court. That court decided that it needed to refer the question to the ECJ, because German law was closely patterned on European Union guidelines for biotechnology patenting.
On March 17, 2011, the ECJ advocate general, Judge Yves Bot, rendered an opinion that even if they do not involve the direct destruction of embryos, techniques involving human embryonic stem cell lines are not patentable because they are tantamount to making industrial use of human embryos, which “would be contrary to ethics and public policy.” This is not a final decision of the ECJ, which will now consider the matter before the entire 13 judges of the court and render an opinion in the next several months; however, it is expected that the court will agree with the advocate general, because it is rare that such preliminary opinions are overruled, according to a court spokesman.
This possibility prompted several stem cell scientists in Europe to send a letter to the court, published in Nature2 , setting forth the case for stem cell patenting. In the letter, the scientists expressed their “profound concern” in their capacities as “coordinators of multinational European stem-cell projects.” They contend that stem cells are cell lines, not embryos, and that they were derived from “surplus in vitro fertilized eggs donated after fertility treatments” that could not be maintained “indefinitely.” The existence of “more than 100” established stem cell lines makes any concern about source embryos “misplaced,” they assert, and warn that it may be “premature to suggest that human embryonic stem cells can be replaced” (by iPS cells, for example) in developing stem cell therapies. A stem cell ban in Europe will prevent scientists from “delivering clinical benefits without the involvement of biological industry,” and such companies “must have patent protection as an incentive” to do their work in Europe. This will result, these scientists predict, in “European discoveries [being] translated into applications elsewhere, at a potential cost to the European citizen.” (sk)
References
1. Bruestle, O. (2006). Neural precursor cells, method for the production and use thereof in neural defect therapy. European patent no. EP1040185. Available at
2. Smith, A. (2011). “No” to ban on stem-cell patents. Nature 472, 418.
Science Wire
The Primary Receptor for AAV9
Knowledge about AAV cell entry pathways has come a long way since AAV was thought to nonspecifically infect cells. Like many other viruses, several AAV serotypes bind to specific glycan components at the cell surface—most often to heparan sulfate proteoglycans or sialylated glycans. Adding to the virus-binding glycan repertoire, two recent independent reports published in JBC 1 and JCI 2 now demonstrate that AAV9 binds to nonsialylated glycans that have a terminal β-galactose.
Both groups first delineated the AAV9 requirement for β-galactose in vitro through a variety of approaches. Glycan involvement in AAV9 biology was tested by addition of various glycosidases to several cell types. Neuraminidase (NA) treatment—which cleaves terminal sialic acid (SA) and exposes the immediately underlying galactose—resulted in a highly pronounced increase in AAV9 surface binding as well as transduction. This result was further tested in CHO cell lines genetically deficient in either SA or galactose, where once again AAV9 binding and transduction significantly increased when galactose was the terminal glycan residue. In addition, lectin competitive inhibition assays were able to decrease AAV9 binding and transduction only with lectins that bind to galactose, further corroborating the conclusion that AAV9 binds to glycans containing terminal β-galactose linkages.
AAV9 is a potentially clinically relevant serotype exhibiting remarkably broad tropism and low immunogenicity. It is able to traverse vascular endothelium barriers, and was recently shown to cross the blood–brain barrier after intravenous injection.3,4 Bell and colleagues thus investigated a potential in vivo relevance for this novel AAV9 uptake mechanism. In the lung, AAV9 has been shown to efficiently transduce alveolar but not the more clinically desirable conducting airway epithelium.5 Remarkably, intranasal coadministration of NA with AAV9 in mice expanded vector tropism to lung airway epithelial cells by exposing galactose at their cell surface. Shen and colleagues also tested the effect of in vivo NA pretreatment on AAV9 nasal instillation, and observed increased transgene expression in murine nasal airway epithelium.1
Collectively, these bodies of work elegantly identify the primary cell entry receptor for a major AAV serotype and support the development of NA as a pharmacological adjuvant to AAV9-mediated gene delivery. (rmt)
References
1. Shen, S., Bryant, K.D., Brown, S.M., et al. (2011). Terminal N-linked galactose is the primary receptor for adeno-associated virus 9. J. Biol. Chem. 286, 13532–13540.
2. Bell, C.L., Vandenberghe, L.H., Bell, P., et al. (2011). The AAV9 receptor and its modification to improve in vivo lung gene transfer in mice. J. Clin. Invest. 121, 2427–2435.
3. Duque, S., Joussemet, B., Riviere, C., et al. (2009). Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol. Ther. 17, 1187–1196.
4. Foust, K.D., Nurre, E., Montgomery, C.L., et al. (2009). Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat. Biotechnol. 27, 59–65.
5. Limberis, M.P., and Wilson, J.M. (2006). Adeno-associated virus serotype 9 vectors transduce murine alveolar and nasal epithelia and can be readministered. Proc. Natl. Acad. Sci. U.S.A. 103, 12993–12998.