NEW YORK, Sept. 12, (GenomeWeb News) -The recent increase in biodefense funding available from the NIH has proved a fruitful way for many genomics and proteomics tool companies to finance technology development.
In Fiscal Year 2003, the US Congress provided $1.7 billion for bioterrorism-related research and development, with most of it going to the National Institute of Allergy and Infectious Diseases. In FY 2004, which begins in October, the NIAID's total budget was increased from nearly $4.0 billion to $4.33 billion, with a proviso for expansion of bioterrorism-related research programs.
The institute said it would support "over 40 new and expanded initiatives in biodefense research," in FY 2003, and has planned for FY 2004 "an additional 17 new and expansion initiatives," according to the NIAID FY 2004 budget.
Some of this research is flowing through major academic centers: Last week, the NIAID announced $350 million in funding to eight Regional Centers of Excellence for Biodefense and Emerging Infectious Diseases, . These centers, which include Duke Harvard Medical School, New York State Department of Health, University of Chicago, University of Maryland, University of Texas Medical Branch, University of Washington, and Washington University in St. Louis. will themselves administer grants to researchers, which in some cases include technology development collaborations between academics and private companies.
For example, in proteomics, which suffuses the basic research being endeavored by the RCEs, Ciphergen has an ongoing collaboration with David Gorenstein at UTMB to develop thioaptamers, aptamers with part-sulfur backbones, on protein chips that would screen for immune response resulting from viral infection. This project will receive additional funding under the $48 million RCE grant that UTMB has received, GenomeWeb News' sister publication ProteoMonitor reported this week, in an overview of the proteomics aspects of the RCE grants.
This also extends to genomics: 454 Life Sciences, the Curagen subsidiary which has developed microbial sequencing technologies, has recently appointed Ian Lipkin, the principal investigator on the New York State Department of Health's $45 million grant for its RCE, to its scientific advisory board. While the company declined to say that it is now working on specific projects in connection with the New York-based RCE, a company spokesman confirmed that they are talking to Lipkin about how to integrate their technologies into such bioterrorism-related research.
"We have every intention of pursuing applications in pharmaceuticals, public health, and biodefense," said the spokesman, Richard Begley. "I don't see anything else out there that can give you the analysis of an entire structure of an organism-total sample in the door to assembled [genome] out the door in a day."
The company's technology, which involves solid phase parallel sequencing within a 300,000 well plate, is particularly suited to distinguishing one strain of organism from another, said Begley for example, "when you want to know what of the 293 strains of anthrax you have," - rather than just basic identification of a type of pathogen. This technology is still in the development phase, according to Begley, and the company will be more willing to talk openly once its researchers have been able to hone the bacterial sequencing capabilities.
Small Companies Ride on SBIR Grant Increase
Other companies, meanwhile, have been funding bioterrorism-related applications of their technology with the NIAID's expanding SBIR/ STTR grant program-which has increased from 222 grants and $60.1 million in FY 2002, to 259 grants and $88.1 million in FY 2003, and is budgeted to include 292 grants and $100.8 million in FY 2004, according to the agency's 2004 budget.
Two of these companies, EraGen Biosciences and Biolog, announced this week that they had received seven-figure grants from NIAID for bioterrorism-related technology research.
Eragen, of Madison, Wis., received a grant of nearly $1 million to develop diagnostics for detection of Class A pathogens - anthrax, botulinim toxin, plague, tularemia, smallpox, and viral hemmoragic fevers.
The two-and-a-half year Phase II grant enables the company to to develop its GeneCode nucleic acid diagnostic technology, following on preliminary research from a $100,000-plus Phase 1 grant . The Phase I grant work involved designing single-plex assays for all of the class A pathogens, said James Prudent, the company's chief scientific officer. In this second phase, the company is developing multiplex assays for these pathogens, and then testing them in collaboration with the US Army Medical Research Institute of Infectious Diseases - the collaborator and customer of choice for many small technology shops getting into this field. The company plans to work with David Norwood, a scientist at USAMRIID, who will do the actual testing of the assays on class A pathogens.
So far, said Prudent, the results on specificity are promising. "What we've been able to show, for example, with smallpox, [is that] the technology is specific enough to detect smallpox in a pool of genomic DNA that actually contains the vaccine genome," he said. "Vaccinia is only different from the smallpox target by a few single base mutations ... and we want to be able to detect the smallpox in someone's blood sample if they've been immunized."
The company hopes to develop a contract business with the Army and the CDC around these pathogen detection applications of GeneCodes.
As advice to other companies who would like to obtain funding from NIAID for bioterrorism-related projects, Prudent - who sits on review committees for NIH technology grants- suggested that "you want to have a technology that is novel, "as well as "compelling data" that will allow the reviewers to be confident that the results can be obtained from the aims that are suggested." But most important "is writing it so someone can understand it," he said. "You want to make it as easy as possible for the reviewers because all the reviewers have their real jobs and are typically pretty busy."
It might also help to have a track record that precedes you.
Biolog, which announced Monday that it had received a $2.28 million, three-and-a-half year SBIR grant from NIAID to further develop its phenotype microarrays as devices for detection and identification of pathogens, has received over 15 NIH and similar grants in its 15-year history.
Tim Mullane, the company's president and CEO, attributed the company's success with these awards to the fact that each grant project "has been successful in developing and commercializing product, and we've been able to report [that] back to the agency."
In the case of this award, the company has already completed the basic technology development for the phenotype microarray, a well-plate containing cell suspensions and specific chemistry assays which allows researchers to compare two cell lines, one with a modification in genes, and one without, and to measure the change in phenotype using a colorimetric indicator of cell respiration.
In applying for the NIAID grant, the company saw an opportunity to use the technology as a means to rapidly detect the presence of microbes. "NIAID wanted to fund technology that would provide better ways of detection microbes - and in particular resistant microbes," said Mullane. This one allows us to do both."
The company is targeting as customers the Department of Energy, USAMRIID, and potentially the US Centers for Disease Control, Mullane said.
In this arena, where there are very few customers, connections with these agencies are key: Biolog has previously developed the bioterrorism database in collaboration with the CDC. This relationship also enables the company, which does not have the lab facilities necessary for containment of Class A pathogens, as the experiments can be performed at the CDC's lab instead.
This relationship with a fully-equipped government facility has also been key for Diversa, which received a $3.2 million grant from NIAID in July to optimize antibodies that the US Army is already using to detect agents of bioterrorism, as well as a $3.7 million grant in August for development of new antibodies.
"If you want a clearly applicable product, you have to have someone like USAMRIID who can work with these [live] pathogens," said Martin Sabarsky, the company's senior director of corporate development . You can't as easily deal with attenuated pathogens, and it's hard to convince your organization to bring in anthrax, or to bring in plague."
Diversa spent almost a year eastablishing its bona fides with USAMRIID, said Sabarsky. "We had several meetings with people at USAMRIID, at the leadership level," he noted, "and also at the scientific level." The company first sought to identify the needs of the defense research establishment, then to try "to match these up to the things that NIAID is funding."
This ability to present both a clear military need as well as a scientific rationale for the technology is one thing that has led the company to be successful in its grant applications, according to Sabarsky.
Currently, Diversa's grant work is focusing on antibodies for anthrax and plague. If the company can demonstrate success with anthrax and plague, they plan to also apply their technology to ricin, botulinim toxin, or tularemia, Sabarsky said. The company then may explore detection of more complex organisms, such as hybrid pathogens that may have been developed by Soviet scientists, and may now be available on the black market.
In addition to optimization of antibodies, and development of new antibodies for detection of pathogens, the company is also looking to develop antibodies that can both detect and neutralize pathogens by knocking out proteins that are responsible for the development of virulence.
"We need to get hopping, so we can identify the key proteins that are the weapons that these bugs use as part of their infectious cycle," Sabarsky said.
This is the first in a series of weekly roundups of biodefense-related technology news in the genomics, proteomics, and systems biology sector. To submit news or for queries about this weekly feature, email [email protected]