The National Advisory Council for Human Genome Research (NACHGR) was convened for its twenty first meeting at 8:30 a.m. on September 11, 1997, at the Holiday Inn, Chevy Chase, Terrace Room A and B. Dr. Francis Collins, drector of the National Human Genome Research Institute, called the meeting to order.
The meeting was open to the public from 8:30 a.m. to 5:30 p.m. on September 11. In accordance with the provisions of Public Law 92-463, the meeting was closed to the public from 8:30 a.m. on September 12 to adjournment September 12 for the review, discussion, and evaluation of grant applications.
Dr. Lennette J. Benjamin
Dr. Aravinda Chakravarti*
Dr. David R. Cox
Dr. Troy Duster
Dr. Ruth Faden*
Dr. Leroy Hood
Dr. H. Robert Horvitz
Dr. Jeanne Lawrence
Dr. Richard Mathies
Dr. Joseph Nadeau
Dr. Diane C. Smith
Dr. David Valle
Dr. Alan R. Williamson
Dr. Barbara Wold
Dr. Ellen W. Clayton
Ms. Rosalie Goldberg, National Society of Genetic Counselors
Dr. Kurt Hirschhorn, American College of Medical Genetics
Jane Ades, OPC
Meg Bouvier, OPC
Joy Boyer, DER
Lisa Brooks, DER
Erin Burgess, OAM
Jean Cahill, OAM
Angela Clear, NHGRI, OTT
Francis Collins, OD
Deidre Davis, OAM
Elise Feingold, DER
Adam Felsenfeld, DER
Leslie Fink, OPC
Mary Glynn, OAM
Bettie Graham, DER
Mark Guyer, DER
Linda Hall, OAM
Linda Jacobson, OAM
Elke Jordan, OD
Ron King, NHGRI, OTT
Eric Meslin, DER
Tara Mowery, OAM
Kenji Nakamura, DER
Diane Patterson, OAM
Jane Peterson, DER
Rudy Pozzatti, DER
Jerry Roberts, CIDR
Michael Royal, OAM
Arline Sanchez, OD
Susan Saylor, DER
Jeffery Schloss, DER
Elizabeth Thomson, DER
James Vennetti, OAM
Monika Yakovich, OAM
Sally York, OAM
David Bailey, Incyte Pharmaceuticals, Inc.
Kristina Borror, NIH/OD
Patrick Brown, Stanford
Ken Buetow, NCI
Robert Cook-Deegan, NAS
Cheryl Corsaro, DRG
Carol Dahl, NCI
Mary Davidson, Alliance of Genetic Support Groups
Ron Davis, Stanford University
Dan Drell, DOE
Rebecca Eisenberg, University. Of Michigan
Steve Ferguson, NIA
Stephen Fodor, Affymetrix, Inc.
Marvin Frazier, DOE
Maria Freire, OD/ OTT
Irene Glowinski, NIGMS
Jim Haight, OD/OTT
Annette Hamburg, NIH/OGC
Philip Harriman, NSF
Lin Hymel, NIGMS
Janet Joy, NAS
Robert Karp, NIAAA
Richard Klausner, NCI
Kathy Ku, Stanford University
Charles Langley, University of California, Davis
Eliot Marshall, Science Magazine
Barbara McGarey, OD/OTT
Joseph McInerney, Biological Sciences Curriculum Study
Jean McKay, NCI
Stephen Mockrin, NHLBI
Robert Molinari, Protogene Laboratories
Lita Nelsen, MIT
Kathy O'Donoghue, College of American Pathologists
Mary Kay Pelias, Office of Senator Domenici
Maria Persinos, Washington Insight
Chris Plaughin, ASCP
Nancy Press, UCLA
Sara Radcliffe, Smith, Kline and Beecham
Walter Schaffer, OD/OER
Robin Siltoen, NAS
Jack Spiegel, OD/OTT
Rebecca Spieler, The Blue Sheet
Marvin Stodolsky, DOE
Robert Strausberg, NCI
Jaconda Wagner, NIH, OTT
LeRoy Walters, Georgetown University
Mona Wan, Stanford University
Dr. Jordan introduced the new council members: Dr. H. Robert Horvitz, Massachusetts Institute of Technology (MIT), and Dr. Alan R. Williamson, Merck Research Laboratories.
Dr. Jordan introduced the liaisons to the Council from the professional societies: Dr. Kurt Hirschhorn, representing the American College of Medical Genetics; and Ms. Rosalie Goldberg, representing the National Society of Genetic Counselors. Dr. Beverly Emanuel, who represents the American Society of Human Genetics, was not present.
The minutes from the May 19 -20, 1997 NACHGR meeting were approved as submitted.
February 12-13, 1998, May 4-5, 1998, and September 14-15, 1998 were approved dates for council meetings. The following dates were proposed for future meetings: February 22-23, 1999; May 17-18, 1999; September 13-14, 1999; February 28-29, 2000; May 22-23, 2000; and September 11-12, 2000. Council members went on record as having a preference for Thursday and Friday meeting dates, rather than Monday and Tuesday dates.
Announcements Dr. Collins indicated that Dr. Lennette Benjamin was rotating off council, and presented her with a letter from Dr. Varmus and a certificate of appreciation.
Dr. Zach Hall, Director of the National Institue of Neurological Disorders and Stroke (NINDS), is resigning for family reasons. Dr. James Snow is retiring as Director of the National Institute on Deafness and Other Communication Disorders (NIDCD). Dr. James Battey, currently director of the NIDCD Division of Intramural Research, will serve as acting director of the institute.
A team of scientists headed by Dr. Frederick R. Blattner at the University of Wisconsin-Madison has determined the complete genome sequence of the E. coli bacterium, with primary funding from NHGRI. E. coli is considered a model organism in the Human Genome Project (HGP). Although not the first bacterial genome to be completed, E. coli is by far the most complex and eagerly awaited by scientists around the world. Dr. Collins indicated this is a milestone of great significance and congratulated Dr. Blattner.
NHGRI researchers, led by Dr. Nussbaum and Dr. Polymeropoulos, have identified a gene abnormality that causes some cases of Parkinson's disease. The gene spells out instructions for a protein called alpha synuclein. In the abnormal version of the gene, the researchers found a mutation in a single base pair - one incorrect letter in the string of more than 400 that compose the instructions for making the protein. Because the normal gene plays a role in the function of nerve cells, the finding gives researchers a powerful new tool for understanding cellular abnormalities in Parkinson's disease and demonstrates the importance of genetic research in seemingly obscure areas.
NHGRI and NINDS scientists working together have identified a gene alteration associated with the fatal childhood cholesterol disorder Niemann-Pick type C (NPC). Learning how the gene functions may lead to the first effective treatment for the disease and a fundamental new understanding of how cholesterol is processed in the body. The disease is widely associated with Ara Parseghian, former head football coach at the University of Notre Dame in Indiana, whose three youngest grandchildren suffer from NPC. NHGRI scientists Dr. Tagle, Dr. Pavan and Dr. Rosenfeld reported these findings.
A team of researchers led by Dr. Eric Green has completed the physical map of chromosome 7. The team spent nearly eight years developing the map of the chromosome, which contains an estimated five percent of the human genetic blueprint.
A new gene, the Amplified Breast Cancer gene (AIB1) has been discovered that is pivotal to a crucial metabolic pathway linked to the growth and progression of human breast cancer. This gene, that influences estrogen receptor activity, will hopefully shed light on breast cancer chemistry. Dr. Trent and Dr. Meltzer spearheaded this research.
A newly discovered gene that causes Alagille syndrome, a rare childhood disease marked by a wide range of birth defects, may be an important key to other human developmental disorders. The mutation in the gene known as JAG1 was discovered by Dr. Collins and Dr. Chandrasekharappa.
An international consortium of researchers, led by Dr. Kastner at NIAMS and Dr. Collins and Dr. Liu at NHGRI, has identified a gene for familial Mediterranean fever (FMF) and found three different gene mutations that cause this inherited rheumatic disease. The gene holds the code for making a protein the researchers call pyrin. They hypothesize that pyrin normally plays a role in keeping inflammation under control, and that mutations in the gene lead to a malfunctioning protein and uncontrolled inflammation.
NHGRI scientist Dr. Anthony Wynshaw-Boris has reported on a knockout of the mouse disheveled-1 gene. Laboratory mice missing this gene show abnormal social behavior. Researchers say their data suggest that the gene and others related to it are candidate genes for several human neuropsychiatric disorders. They expect the mouse mutants to prove useful in studying aspects of these human neuropsychiatric disorders, and possibly in testing new drug treatments.
Appropriations for FY 1998 Debate continues in the House and Senate on appropriations bills for Health and Human Services. However, it is anticipated that bills will pass within the next couple of weeks. The House has proposed a 6 percent increase for NIH over the 1997 Budget, with a 12.1 percent increase for NHGRI. The Senate is proposing a 7.5 percent increase for NIH over the 1997 Budget, with a 15.8 percent increase for NHGRI. In general, there is bipartisan support for NIH within Congress, and Congress is particularly supportive of NHGRI.
Dr. Collins noted that President Clinton has taken a personal interest in health insurance reform. As reported at the May council meeting, in a May 18, 1997 commencement address at Morgan State University, President Clinton " urge(d) Congress to pass bipartisan legislation to prohibit insurance companies from using genetic screening information to determine premium rates or eligibility for health insurance." On July 14, 1997, President Clinton held a follow-up Genetic Screening Event at the White House to announce that his Administration would support specific legislation to prohibit insurance companies from using genetic screeining information to determine the premium rates or eligibility of Americans for health insurance. Members of patient advocacy groups, professional societies, genetics researchers and policy makers gathered in the East Room of the White House to witness the President's announcement. The President also announced that Senator Frist from Tennessee and Senator Jeffords from Vermont have indicated that they will work with the Administration to pass bipartisan legislation to ban discrimination based on genetic tests. In addition to the President, speakers at the event included Department of Health and Human Services (DHHS) Secretary Donna Shalala, Representative Louise Slaughter, and breast cancer activist Mary Jo Ellis Kahn. This is an example of how recommendations of the ELSI Working Group in collaboration with the National Action Plan on Breast Cancer (NAPBC) have resulted in national policy.
On July 22, the Task Force on Health Records and Genetic Privacy, co-chaired by Representatives Clifford Stearns (R-FL) and Gene Green (D-TX) held a hearing on "Privacy, Confidentiality and Discrimination in Genetics." Witnesses included Dr. Francis S. Collins, and representatives of academic research institutions, advocacy groups, and pharmacological and biotechnology companies. The purpose of this meeting was to gather information about genetic discrimination and confidentiality from producers and users of this information and identify options that may be used to prevent genetic discrimination.
On July 22, Senate Minority Leader Tom Daschle (D-SD) introduced The Genetic Justice Act, which follows the recommendations on the use of genetic information in the workplace developed by the National Action Plan on Breast Cancer (NAPBC) and the ELSI Working Group and published in Science (March 21, 1997, vol. 275).
On July 25, Representative Nita Lowey (D-NY) introduced an identical companion bill to Senator Daschle's, H.R. 2275, the Genetic Employment Protection Act of 1997.
Recently on September 5, 1997, Vice President Al Gore, in an address to the Dartmouth Medical Symposium in Hanover, New Hampshire, indicated the Administration's commitment to preventing genetic discrimination in the workplace.
There is less consensus regarding issues of privacy and medical records confidentiality. The Secretary of HHS is currently working on guidelines "with respect to the privacy of individually identifiable health information" which will be delivered to Congress in September. These recommendations will apply to medical records on patient care, including patient care provided under a research project. However, information collected or generated purely as part of a research project would not be included.
NHGRI and NAPBC will be hosting a workshop to stimulate policy options for maintaining the privacy and confidentiality of genetic information in medical research. The workshop will be held September 16 and 17 in Bethesda, Md.
The American Medical Association (AMA) will host a meeting in March, 1998, entitled "Genetic Medicine and Primary Care: The New Era." The meeting will take place in New Orleans, and is being planned in partnership with the NHGRI, the American Society of Human Genetics, and a number of professional medical groups. This is an effort by the AMA to reach out to physicians in the community who must deal with genetics issues when giving primary care to their patients. Another part of the AMA initiative is a genetics theme issue of the Journal of the American Medical Association focusing on genetics educational issues and challenges, slated for publication in October 1997.
The CGSC met on September 8 and 9, 1997, to allow the CGSC investigators an opportunity to receive updates on current research projects and discuss common areas of concern, including the psychosocial issues arising from susceptibility to cancer. The group was funded for three years and is now considering what format it should take in the future. Dr. Collins thanked Elizabeth Thomson for her management of this group.
On October 15 and 16 there will be a follow-up workshop on the Cystic Fibrosis Consensus Conference Recommendations co-chaired by Dr. Michael Mennuti of the University of Pennsylvania and Dr. Nancy Press,, of UCLA. This meeting is being hosted by NHGRI, together with the NIH Office of Rare Diseases (ORD), Office of Medical Applications Research, National Institute of Child Health and Human Development (NICHD), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institute of Mental Health (NIMH), National Institute of Nursing Research (NINR), Centers for Disease Control and Prevention (CDC) and AHCPR to bring together researchers and representatives of relevant organizations to examine the recommendations from the Consensus Development Conference on Genetic Testing for Cystic Fibrosis. Participants will develop guidance about if, when and how these recommendations should be implemented and communicate the outcomes back to their organizations.
The ELSI Evaluation Committee, chaired by Dr. Anne Spence and Dr. Mark Rothstein, made recommendations in December 1996 to divide up the functions of the ELSI Working Group. One of the recommendations led to the creation of the NHGRI-DOE ELSI Research, Planning and Evaluation Group (ERPEG), which held its first meeting on September 10, 1997, with Dr. LeRoy Walters as Chair. The purpose of the meeting was to orient ERPEG members to the programs at NHGRI and DOE and begin developing a strategy for the review and future planning of ELSI Research program activities. NHGRI is mandated by Congress to spend 5 percent of its budget for ELSI activities, and DOE spends 3 percent. ERPEG members will be reviewing the ELSI portfolio to see that these dollars are being spent wisely.
Responding to another recommendation of the Spence/Rothstein group concerning the need for communications and coordination, Dr. Varmus has established a Trans-NIH ELSI Coordinating Committee, chaired by Dr. Lana Skirboll in the Office of the Director. This committee will consist of representatives designated by each NIH IC director. Dr. Eric Meslin has been named the NHGRI representative.
A third recommendation of the Spence/Rothstein group indicated a need for an advisory group at the department level to advise on the introduction of new genetic tests, etc. The activities of this group should not conflict with the National Bioethics Advisory Commission. The department is considering this recommendation.
The official report of the Task Force on Genetic Testing has been sent to the printer and will be available shortly.
Dr. Marvin Frazier sent regrets from Dr. Ari Patrinos who was unable to attend and gave an update on activities at the Department of Energey (DOE). Regarding the budget, the House and Senate numbers are close, and the DOE does not anticipate significant changes from their request. However, Dr. Frazier assured council that the HGP would be protected no matter what the final budget outcome.
The Microbial Genome Program has been successful in sequencing three additional microbial genomes this year and the data are available. DOE has now completed the sequencing of five genomes of diverse microorganisms.
Dr. Patrinos and Dr. Frazier have spent considerable time organizing the DOE's Joint Genome Institute (JGI). Initially the JGI consists of an amalgamation of the efforts at Lawrence Berkley National Laboratory, Lawrence Livermore National Laboratory, and Los Alamos National Laboratory. In time it will encompass the whole DOE HGP. This will be a community effort involving collaboration with researchers at other sites contributing new sequencing technologies. The first peer review of the JGI plan was held August 16, 1997 in Bethesda, Md. Within the month, DOE will be transmitting the reviewers' comments along with recommendations to the JGI.
The JASON review group, consisting of scientists in various fields, particularly from physics, has completed their review of the DOE HGP and the final report is expected by November. This report will be shared with NHGRI.
DOE is beginning to restructure its informatics efforts. This involves the Genome Sequence DataBase, the Genome DataBase, and the DOE Annotation Consortium. The plan is to develop a new scope of work and to develop better collaboration between the disparate DOE informatics efforts. The focus will be to make these informatics efforts more user friendly and useful to the genomics and biological communities.
DOE's ELSI program continues to have very productive interactions with the nation's judges through a series of workshops that inform the judges about the various DNA technologies that they will face in their courtrooms. The workshops provide a tutorial on the genome program and the use of DNA evidence in legal cases.
There will be a DOE-sponsored program airing on PBS on Tuesday entitled "A Question of Genes."
Dr. Frazier indicated that DOE continues to be very interested in the development of the new 5-year plan for the HGP and would like to be a full partner in the process that NHGRI has initiated.
Dr. Mark Guyer presented a series of five tables (see attached) that are being used in budget planning, particularly for considering new scientific opportunities in FY 1998 through FY 2000. These tables project how much money we expect to receive in appropriations, what we currently plan to spend, and what will be available to start new programs.
Table 1 lists all our current commitments, i.e. the commitments entailed in the NHGRI grants made in FY 1995, 1996 and 1997. The table is organized according to the HGP goals and gives an overall view of how NHGRI funds are currently distributed across those goals. These are non-competing commitments, and this is money we are obliged to spend. The table gives a baseline of where we are now.
Table 2 lists the competing funds (and their future year commitments) that we are planning to spend in FY 1998 on program areas that have already been approved, and are being implemented. The largest commitment is for human production sequencing. The HGP plans on completing the first reference human DNA sequence by 2005. Assuming that sequencing costs will continue to decrease, we estimate that NHGRI will need $60 million a year to complete its contribution (ca. 1.8 billion base pairs) to the completion of the human genome sequence by that time. Other projects that we are committed to include mouse EST mapping, development of new sequencing technology, completion of the Drosophila genome sequence, support for certain public databases, and the annual 5 percent budget set-aside for ELSI activities.
Table 3 is a summation of the numbers in Tables 1 and 2, and indicates the total commitments in each fiscal year between now and FY 2000. It gives the overall view of the way in which NHGRI funds that are already planned or committed will be distributed across the genome project goals for the next three years.
Table 4 shows the estimate of how much competing money will be left for additional spending in each of the next three fiscal years. The numbers in Table 4 were calculated on the basis of the budget that has already been passed by the House of Representatives (the "House Allowance"). We estimate that $23 million will be available for new programs in FY 1998; $18.5 million in FY 1999, and $15 million in FY 2000.
Table 5 shows estimates for the amount of competing money that will be left for additional spending in each of the next three years according to two other scenarios: the President's Budget (lower than the House Allowance) and the Senate Allowance (higher than the House Allowance).
Dr. Collins noted that these are conservative estimates and only project an annual 3 percent budget increase. In reality, the increase could be larger. For instance, the Senate has already proposed to double the NIH budget over the next 5 years. Dr. Jordan pointed out the table on the "Funding History of the National Human Genome Research Institute" showing the growth of the extramural and intramural research programs, which has consistently exceeded 3 percent each year.
Dr. Mathies warned that we should not be constrained by estimates that are too conservative. We should be talking to other ICs, like NCI, about new projects. He also strongly encouraged the institute to continue to support technology development in the face of other continuing demands for those funds. He also stated his opinion that we need to be prepared for additional expenditures for other organisms.
Dr. Collins introduced Dr. Alan Williamson, Vice President of Research Strategy Worldwide, Merck Research Laboratories, and member of the NACHGR. Dr. Williamson served as moderator for the presentation and ensuing discussion of three case studies that exemplify motivations and complexities underlying current patenting and licensing practices for molecular biology tools and genomic data, and the potential impact of these practices on research progress.
In addition to those individuals who were specifically invited to present points of view at this workshop, and the council members, liaisons and staff who participated, several additional guests contributed important ideas to the discussion. These included Kathy Ku, director, Stanford Office of Technology Licensing; Lita Nelson, director, MIT Technology Licensing Office; Dr. Maria Freire, Office of Technology Transfer, NIH; and Dr. Robert Strausberg, NCI.
In his introductory remarks, Dr. Williamson characterized the HGP as the most important scientific project ever conceived. Its ultimate goal goes beyond determining the complete sequence of human DNA to understanding the very basis of life. However, the continued success of the genome project and of future biomedical research depend upon access by researchers and the public to new research tools and the information that results from their use. While the patent and licensing system in the United States was established to protect intellectual property and stimulate the further development of creative, useful invention, some researchers feel that access to many of these tools and information are, perhaps unintentionally, being restricted through the application of patent laws and through exclusive licensing agreements. He challenged those present to think about ways in which to ensure that the world's scientists will be able to use the data and have access to technologies that are needed to exploit those data.
Dr. Rebecca S. Eisenberg, professor of law at the University of Michigan Law School, presented a perspective on patent law and genomic discovery. Patents serve an important function by motivating and protecting investment. Intellectual property protection is needed because successful innovation is costly and risky, but cheap to copy. On the other hand, patents can create monopolies, restrict access and allow firms to raise prices. A key question is whether any particular technology would be developed in the absence of patent protection, and, if so, are there ways to foresee that and conduct patenting and licensing accordingly?
Companies want to control the intellectual property on products they sell to their customers. Pharmaceutical companies patent the drugs they sell to the public and would prefer that the tools needed to discover those drugs be freely available. However, the genomic data and the research tools required for drug discovery are in many cases produced by biotech companies, which therefore have an interest in protecting them. In other words, one firm's research tool is another's product.
A series of events court decisions defining what can be patented, the explosion of companies that occupy niches closer to the lab bench than to consumer products, and the passage of Bayh-Dole and other legislation that encourages firms and research institutions to patent and license discoveries to keep them from languishing have created an environment in which early-stage discoveries are much more likely to be patented and access to them restricted. In this environment, patents exist on early-stage tools that have a limited audience of potential users. If that audience has limited funds (e.g. the academic community or another small biotech), or is itself generating products with uncertain markets or the successful development of which is risky, the supplier must figure out how to generate the revenues needed to continue its activity and the customer must figure out how to pay for the information or research tools it needs. The solution is often to establish reach-through rights to products that the customer has not yet produced. Additionally, a large number of different entities now hold the intellectual property for the many different tools that are required for the discovery process. Potential users must therefore establish many different agreements if they are to gain access to the array of tools, and this requires substantial legal effort and money. Even for those researchers that have access to the legal advice and funding, and certainly for those that do not, this system results in a potential impediment to research.
Finding solutions to the perceived problem of the rush to patenting is not easy. Defining categories of discoveries that should be excluded from patents, or that should receive research exemptions, is very difficult. If accomplished, this might lead to loss of development, or secrecy, which is worse than any restrictions that may result from patenting/licensing. A community can refuse to accept "unreasonable" licensing practices, but this will fail if there are a handful of groups that are willing to accept those practices. And a push to publicly fund an initiative, and require as a condition of award a commitment to wide-spread availability of the results, requires that the public sector be ahead of the private sector, and also violates the Bayh-Dole act.
Dr. Jeffery Schloss introduced the first case study, access to oligonucleotide synthesizers, by describing the multiple uses of oligonucleotides in genomics laboratories and the perceived need to incorporate high throughput synthesizers, on-site, into automated systems in order to achieve efficiency in large-scale operations. However, a machine invented at Stanford University was patented and licensed exclusively to a company that does not wish to produce machines for sale. Instead, the machine is used to synthesize oligonucleotides, which are then sold to the consumers. As a result of introduction of this machine, the price that consumers pay for oligonucleotides has decreased substantially, benefiting the entire molecular biology community. The speakers for this case study were Ronald Davis of Stanford University, in whose NHGRI-funded laboratory an oligonucleotide synthesizer was developed under the leadership of Thomas Brennan, the patent holder, with funding from the DOE human genome project; Mona Wan, the specialist in the Office of Technology Licensing at Stanford who negotiated the license for the technology, and Robert Molinari, President and CEO of Protogene Laboratories, the exclusive licensee.
Dr. Ronald Davis, Professor of Biochemistry and Genetics in the Department of Biochemistry, Stanford University School of Medicine, described the development of the instrument. He and the university were unable to identify a company that would produce the instrument for commercial distribution. The instrument was considered too complex and failure-prone, and investigators were not interested in it because it made more oligonucleotides than their research required. Even genome centers said they preferred to purchase oligos rather than make them in-house. Attempts to publish the work in 1993 were rejected on the basis that oligonucleotide synthesis was not new and the research community was not interested in such a machine. Therefore, the instrument was licensed to Protogene, which, in partnership with Life Technologies, used the instrument to synthesize custom oligonucleotides for sale to the molecular biology community. Stanford retains use of the machine, and its use in Davis' lab, for example, to build oligos for a yeast functional genomics study that requires 2 million coupling reactions. Ninety-seven percent of the oligos that are synthesized work in the assays for which they are designed, and therefore no quality control tests are used (see below, page 14).
Ms. Mona Wan, a Senior Licensing Associate in the Office of Technology Licensing at Stanford University, explained that the role of her office is to transfer technology for the public good and generate revenue for the university. She stated that potential licensees contacted by her office concluded that the market for building these instruments for sale was too limited. On the other hand, a company that would license the instrument for in-house use, to produce oligonucleotides for sale, could make a profit while reducing the cost of oligos to a very broad community, resulting in substantial cost savings for research and an increase in the potential to discover new ways to use oligos for research. Therefore the device was licensed to Protogene, a company started by Dr. Thomas Brennan, the inventor, with rights reserved for Stanford to use the device. The university considers this a classic case of successful technology transfer because a large community of users (not just those who could have afforded to purchase the machine) benefitted from the new technology. Ms. Wan stated that no other company has approached the university for a license, although one academic institution has done so.
Dr. Robert Molinari, founding President and CEO of Protogene, summarized the history of his company. Protogene was incorporated in January 1994. In April 1994 Protogene received the exclusive license for the oligo synthesizer from Stanford, and a month later entered a partnership with Life Technologies, under which Protogene would improve the technology and Life Technologies would be responsible for marketing. An exclusive license was essential to protect the large investment both companies had to make, to build in the capacity to satisfy customer demand for oligos of a range of sizes and chemical modifications, and to develop systems for efficient ordering, order tracking, quality control, and delivery. Private investment would not have occurred, had there been constraints on the license. In October 1994 the first production DNA was sold to NCI. The company turned profitable a year after it was formed, and by October 1995, Life Technologies was the largest manufacturer of DNA in the world.
As a result of this venture, DNA prices decreased from $2.50/base in January 1994 to $0.49 per base for volume users today. Competitors also had to lower their prices. A small amount of government investment ($300,000 from the DOE) in this project led to substantial private investment ($2M to $3M), and the entire research community benefited. The U.S. research community saved $30 million on oligonucleotide costs in the first two years and Stanford has been able to set up scholarships from the revenue it has received.
Dr. Molinari concluded that government grants should be small and catalytic in nature; they should never be so large as to determine the success of one technology over another. Licenses must be written to ensure performance. Private sector incentives must be allowed to continue.
In answer to questions raised at the beginning of the discussion period, Mona Wan indicated that Stanford licensed the technology based upon a patent application, does not receive reach through royalties, and receives royalties based on a percentage of sales.
Dr. David Cox (Stanford University) stated that his lab's cost of producing oligos with the machine is much less than $0.50/base, so there are benefits to having the machine. But this is achieved in part by forfeiting quality control (Dr. Davis stated that so few oligos fail that it is more economical simply to remake failed oligos rather than doing quality control). However, he questioned whether very many sites could support an instrument of this complexity and stated that the exclusive license had resulted in widespread benefit. Dr. Molinari concurred with the latter points, stating that 80 percent of the customers (of which 60 percent are academics, 40 percent in industry) order fewer than 10 oligos.
Dr. Collins suggested that primer walking sequencing might be practical if high-throughput oligonucleotide synthesizers were incorporated into sequencing automation pipelines in genome sequencing centers. He asked if Protogene/LTI fulfills the needs of such centers.
Dr. Molinari said that 24-hour turnaround time is now the industry standard for oligonucleotide suppliers, so this might fulfill the needs of such centers. He stated that Protogene is willing to consider building a few machines and sublicensing them, but finds it hard to imagine that most sites could maintain the instrument. Two genome centers have requested sub-licenses, but their proposals were rejected because they would not agree to the offered terms. Two sublicenses have been granted for combinatorial chemistry.
In response to Dr. Collins's question about the breadth of the patent, Dr. Molinari stated that it is a mechanical patent that does not cover 96-well synthesis, per se, and could be invented around. When asked how Protogene would respond if a genome center built a machine without a sublicense, Dr. Molinari said that the company would respond, but admitted that the company would be unwise to sue its largest customers. Ms. Wan pointed out that the company would have to consult with Stanford before litigating against an academic institution, and Ms. Kathy Ku, of the Stanford Office of Technology Licensing , stated that the office has litigated only two cases in 26 years and prefers to resolve such issues by discussion with the involved parties.
Questions were raised about the extent of applicability of the government's license to freely use technologies developed with government support. The opinions expressed varied as to whether this right applies to projects supported by government grants. Dr. Molinari stated that this is an area of uncertainty, about which the private sector is nervous.
Barbara Wold described the potential to use high density DNA arrays for a variety of fundamental studies. This technology represents a logical progression from techniques used in molecular biology since the 1970's, but would allow scientists to do the studies they could previously only contemplate. From the perspective of potential users, the relevant questions about this technology, and their desired answers, are: Can I get it? YES. When can I get it? YESTERDAY. How much will it cost? NOT MUCH.
Dr. Stephen Fodor, President and Chief Executive Officer of Affymetrix, Inc. summarized the path to developing this technology, which has been costly and is not yet complete. Dr. Fodor reminded the council that Affymetrix devised the means for designing, producing, and packaging the chips; and for achieving high quality and reproducibility in the manufacturing process. They have developed and produced instrumentation, assay systems, and software for using the chips. Commercialization requires that the instruments and assays be robust and exportable, and systems must be in place to support users and meet demand. The company and technology have been built from the ground up. To accomplish this, about $150 million has been raised and most of it spent. This investment must be protected. Other companies, notably Molecular Dynamics and Hewlett Packard, are involved in the implementation of the technology, and they are also in this to generate profit.
The technology has the potential to be used to answer questions such as: Is a particular sequence present in a DNA sample? Where does that sequence map relative to already mapped sequences? What is the amplitude of expression of that sequence in a sample? How does the nucleotide sequence present in a particular sample vary from a canonical sequence? To produce chips that will allow scientists to answer such questions, Affymetrix must be able to place query sequences on chips. Therefore, ownership of intellectual property on potential query sequences is an important issue for the company. For mutation detection and ESTs, some of the sequences scientists want to assay are in the public domain and others are the subjects of patents. Affymetrix plans to sell a chip for screening of 2000 human DNA sequence polymorphisms; this can only be accomplished if sufficient numbers of polymorphisms are discovered and if Affymetrix is not blocked from building chips that use them. Other companies have similar plans, and each wants to profit from its investments. The surest way to protect one's right to use the sequences is to hold the relevant intellectual property.
Affymetrix is taking several routes to provide access to this technology. Commercial deals give early access to technology that is of high value to the partners, and provides funds and feedback to the developer. This type of access has only recently been pursued and is rapidly expanding; three years ago nobody wanted it because they perceived it as overkill. Individual collaborations come to a user center at the company, and far outnumber the commercial deals, but the company has limited capacity to pursue these. Some of these collaborations are supported by NIH funding. Affymetrix is pursing the idea of setting up academic centers, where the company would deal with a point person who knows the technology and others would use that person and the equipment as a resource. Finally, they are working toward large-scale export.
Dr. Patrick Brown, Associate Professor of Biochemistry and Genetics at the Stanford University School of Medicine, described the rationale for developing microarray technology in his laboratory. He wanted to be able to array large numbers of genomic DNA samples that span the genome, and probe these with a mixture of two differentially labeled nucleic acid samples derived from paired material (such as tumor cells and their normal counterparts). Comparison of the hybridization signals would reveal sequences that were present at different levels in the two samples.
Dr. Brown conceived of a simple robotic device that would lay down droplets of solution or suspensions of biological material on a nonporous surface such as a glass slide. However, he was unable to interest Stanford engineering faculty or students in building such a device because they didn't consider it to be a sufficient challenge. He finally identified a rotation student who was willing to build the device in exchange for first rights of commercialization.
A year after initiating the work, the student, Dari Shalon, formed a company called Synteni, and licensed the device from Stanford. Synteni wanted an exclusive license for the technology. The Stanford Office of Technology Licensing overruled that request initially, and sought other licensees. However, Synteni received the exclusive license when the Office of Technology Licensing was unable to identify other potential licensees. Synteni's original strategy was to commercialize the device and make it widely available, but that strategy has changed to one of selling services that use the technology. A few other companies have developed devices for this patent pending technology.
Brown's lab is placing instructions for building the device on a web page and has plans to make a video to explain its construction and use. His lab relies heavily on access to this technology and he considers it to be a basic tool of high potential utility to many labs because of its low cost, ease of use, and great flexibility to redesign and build new arrays rapidly.
A vigorous discussion followed Dr. Brown's presentation. One topic was the adequacy of the method for marketing of the technology prior to licensing. Perhaps publishing an abstract that is widely distributed is a better means of gauging interest than is sending a letter to a select group of companies. This might reach larger numbers of potential licensees, and could also be used to solicit broader advice on the potential uses of the technology (and thus the impact that a broad exclusive license would have on the research community). If exclusive licenses are to be granted, they might be for a limited field of use.
Dr. Hood suggested that the determination of whether to grant exclusive license for a particular technology should take into account the amount of investment and time needed to bring that technology to market. He cited as examples the automated DNA sequencer and the Affymetrix chips which required investment of many tens of millions of dollars over several years, and which would therefore be unlikely to be developed without exclusive license. Other technologies might be brought to market much more readily and therefore not require exclusivity. Dr. Molinari pointed out that there are relief valves for the research community, with respect to technologies that take a long time to develop or are expensive to acquire; these may exist in the form of pre- existing technologies, or subsequently developed technologies, that allow the user to circumvent the expensive technologies and still accomplish the work. In all of these cases, competition should be allowed to work.
A second issue was whether the current licensee is living up to the government's requirement for dissemination of the technology by the licensee. The Stanford Office of Technology Licensing believes it is too early to say that research is being impeded, because the company is still trying to develop and market the product.
It was suggested that Dr. Brown's laboratory could provide access to the technology through large-scale collaborations, thus keeping the use of the technology per se restricted to Stanford. However, this would require substantial paperwork for Materials Transfer Agreements which Dr. Brown prefers not to pursue.
The patent for this technology has not yet been issued. Licensing of patents that have yet to issue has a variety of complicated outcomes. It is not clear what claims will be granted. In some cases, development of similar or identical technology by other groups, with potentially overlapping commercial interests, may or may not by impeded. The inventor is unsure as to what steps can be taken to assist in disseminating the technology (for example, by producing videos on its use). Potential academic users may decide to take the chance of replicating an instrument, assuming that they won't be sued because they are "just using it for research." But research exemptions are not codified and liabilities could result, even if a technology licensing office tries to "jawbone" the licensee against prosecuting academic users. Or the academic user may assume that s/he cannot use the technology because it has been exclusively licensed. However, until the patent issues, the public is free to use the technology. The claims actually granted may be much more limited than those claimed, reducing any risk that the user may take in setting up the technology in his or her laboratory. One could gamble on setting up the technology and hoping that by the time the patent issues, competition and alternative technologies would reduce both any potential liability and the price for sublicensing or purchasing technology from the licensee. All of these facts notwithstanding, the indeterminate nature of these issues is likely to result in ambivalence on the part of any individual researcher or a community to adopt the technology, thus effectively limiting access to that technology.
Dr. Mark Guyer introduced the third case study concerning single nucleotide polymorphisms (SNPs), the most common type of human DNA sequence variation. SNPs are of increasing interest because they are relatively easy to discover and score, they can be used to construct genetic maps, and some of them will be connected to phenotypes. There are many SNPs in the genome, but it is a bounded information set, and the SNPs that occur in genes or gene regulatory regions are even a more tightly bounded set. It appears likely that patents would be granted on SNPs, and therefore people are becoming concerned that access to the use of this unique information about the human genome might become restricted. Even if others were allowed to use SNP collections on which there are patents, substantial reach-through rights on discoveries made with that information might be sought by the patent holders. Such restrictions and reach-through would very likely inhibit research progress. The goal of this discussion was to arrive at some mechanisms for ensuring wide and ready access to SNPs.
Dr. David Bailey, Vice President of Pharmacogenomics at Incyte Pharmaceuticals, Inc., indicated that discovery of SNPs requires substantial investment, and that once discovered they are of great value not only as genetic markers, but also as the key to conducting pharmacogenomic studies that will allow scientists to discern patient populations that respond to particular drugs. Accomplishing studies like this requires a very large investment, which exceeds the funds available in academic environments. Further, the studies involve large, interdisciplinary teams that require effective management, and levels of data logging and quality control not normally achievable in an academic setting. So while there is wide agreement that access by academic investigators to information such as SNPs is of great importance, it is also important to ensure that the infrastructure is available to use SNP data effectively, and that the locus of that infrastructure has the necessary access to SNP data.
Dr. David Cox agreed that an information infrastructure is needed to effectively utilize SNPs, but argued that this would most effectively reside in the public sector. It is important that different groups all have access to the same SNPs. If different companies assemble their own SNP collections, they will end up creating data sets that cannot be cross-validated. And the latter is what is ultimately important. We need to invest in the development of technologies and informatics to discover, assay, and map SNPs, but to make these data truly useful we must also be able to associate them with phenotypes across the population. This is a much bigger problem than any single clinical trial or small set of clinical trials needed for discovering a few drugs. If each company has a data set and does some studies, each will have only part of the story. If the data are public, and different groups can use the same SNPs so the data can be compared across studies, the full benefit of the data can be realized.
Discussion concerning ownership of SNPs ensued. Some expressed concern that if a company does not own the intellectual property on SNPs, it would not be able to use them for the assays it requires, because someone else could block that use. Others suggested that patents would be acceptable if there were extensive, non-exclusive cross-licensing with acceptable terms, or if the SNPs were in the public domain so that all could use them equally. In fact, it is not clear whether SNPs will receive patent protection.
Different companies have different stakes in these issues. Dr. Bailey stated that Incyte might not wish to patent or market SNPs, but might market the data from which SNPs might be discovered. Dr. Fodor stated that much work goes into sorting through databases of potential SNP information to identify the ones that are real. He indicated that Affymetrix technology could be used to do that work, and the company is open to making arrangements with the community for that information to be publicly available. Dr. Chakravarti noted that such a database of SNPs is of indeterminate value because much further work is needed to sort through the significance and prevalence of any polymorphisms in it. Dr. Collins pointed out the distinction between polymorphisms in coding and obvious gene regulatory regions, versus those randomly distributed throughout the genome. It is obvious that the former would be of the greatest functional significance, so they are likely to be the ones sought and developed in the near term. This is a relatively small set of relatively high value information. Even with the possibility of cross- licensing, it would be very troublesome if one had to establish numerous licenses before one could do an experiment.
Two general routes to solving the potential problems surrounding intellectual property restrictions to access to SNPs were then discussed. These were in the areas of education and private/public sector cooperation. Dr. Jeanne Lawrence suggested that NHGRI issue public statements that SNPs are obvious, in an attempt to influence the action of patent examiners who will determine patentability for SNPs. Dr. Freire noted that, during discussion on ESTs, the NIH OTT extended to the Patent and Trademark Office an offer to engage in a dialogue, and suggested that we use this subject to pursue this opportunity. Dr Lawrence also suggested an effort to educate investigators on the importance of placing such data in the public domain.
A second solution that could be pursued in parallel with education would be to establish a public/private consortium to work with the available technology platform owners to generate the data and place it in public databases. Such an effort was introduced by Dr. Collins at the previous week's meeting of the directors of the NIH ICDs. Dr. Mathies suggested that this could be accomplished by assembling groups of grantees to determine what information should be placed on chips, and by enlisting the joint efforts of concerned agencies to establish funding to pay for the development of those chips. This would address the companies' concern about the time and cost of developing the reagents needed to satisfy various communities. Dr. Fodor asserted that such an arrangement eliminates uncertainty for both the companies, the agencies, and the grantees. Dr. Bailey stated that Incyte might be keen on such an arrangement, which would add more SNPs to the public databases and therefore more value to Incyte's products. Merck clearly would not be threatened by such an arrangement, as evidenced by its contributions to making publicly accessible large numbers of EST sequences. Drs. Collins and Williamson noted that such an arrangement would provide wide access while obviating the need for cross-licensing. Dr. Lita Nelson added that such a public consensus about the importance of public access to human variation data would assist the university tech transfer offices in conducting their affairs related to human sequence variation. They would be much less likely to pursue patents on such data generated within their institutions. University tech transfer offices want to do the right thing. Dr. Eisenberg noted that this puts the universities in the role of owner and ignores the universities' parallel role as consumer, which should help to guide it to doing the right thing. Dr. Freire cautioned that consortia might well result in some data being place in the public domain, but other groups that do not agree to join can continue to go their own way.
Dr. Mathies suggested that if sufficient funds could not be assembled to pay for such an arrangement, the companies could retain reach-through rights to allow the collaboration to move forward. Dr. Wold expressed lack of enthusiasm for this approach and Dr. Williamson likened it to paying for the wedding by selling the firstborn. Dr. Fodor indicated that reach-through was not an optimal solution for Affymetrix because of the uncertainty it entails, and Dr. Nelson cited an example where such an arrangement prevented a more desirable arrangement. Dr. Freire expressed the concern, from a public health perspective, that the resulting stacking might prevent subsequent investment that is needed to bring discoveries to the public good.
Dr. Freire pointed out that the Patent Office does not see itself in a policy making role. We should partner with that office rather than try to pre-empt it. The NIH Office of Technology Transfer has already extended an offer to dialog with the Patent Office.
Dr. Williamson concluded that the council should publish its views to educate the public, the research community, universities, and other agencies of the government. A consortium to discover SNPs and place them in the public domain should be pursued, but we should remain aware that others who were not present for this discussion may object. It is in the public's interest that we seek ways to continue developing technologies and information to which consumers have access, because this will advance the intent of the Bayh-Dole legislation.
Dr. Chakravarti indicated that the 10 members of the Council Planning Subcommittee had their first formal meeting on September 9 and 10, 1997 to discuss future scientific priorities of the NHGRI. He described some of the topics that were discussed, including completion of human DNA sequencing and studies on sequence variation. The Committee is planning a Function Workshop in December to focus on potential genome-wide studies of gene function. The workshop will lay out the kinds of studies that NHGRI could support and what they will add to interpreting sequence. Dr. Chakravarti indicated that the Planning Subcommittee and the ELSI Research Planning Evaluation Group had met at lunch to keep each other informed of their activities.
Dr. LeRoy Walters reported on the first ELSI Research Planning and Evaluation Group (ERPEG) meeting held September 10, 1997. This committee was formed as the result of a recommendation by the ELSI Evaluation Committee chaired by Dr. Spence and Dr. Rothstein. The proposed mission of the ERPEG is "to provide the NHGRI and the OHER/DOE with expert guidance on matters relating to their extramural ELSI research portfolios. This mission is understood to include long range planning and evaluation activities." The committee is a working group of the council and the DOE Health and Environmental Research Advisory Committee (HERAC); is comprised of nine members, including an individual from the general public and two individuals from the Council; and is staffed by the NHGRI ELSI Research Program. Dr. Walters indicated that the ERPEG expects to produce a preliminary report by next May.
At their first meeting, ERPEG members initially met with NHGRI and DOE staff to be given an introduction to ELSI programs and an overview of their mission. The group met with members of the Planning Subcommittee at lunch to discuss policy and ethical issues. In the afternoon, the ERPEG members set up three subgroups. The first group will be process oriented and focus on how to get input into ELSI issues. This group plans to talk with members of the American Society of Human Genetics and set up a Web site. The second subgroup will be charged with reviewing the ELSI portfolio and identifying any gaps in existing support. The third subgroup will be asked to "think outside the box" and come up with ethical issues not currently covered. The complete committee plans to meet again in December and February, and possibly in April.
Dr. Jane Peterson presented information about an RFA to be published in late winter or early spring to solicit applications to participate in a research network, which will be responsible for completing the NHGRI share of the sequence of the human genome by 2005.
Dr. Peterson indicated that the goal of the NHGRI large-scale sequencing program is to contribute to the completion of the first human DNA sequence by 2005. It is assumed that NHGRI would be responsible for producing about 60 percent of the total human sequence (1.8 billion base pairs), with the remainder to be contributed by partners in the Human Genome Project. Completion of NHGRI's share of the sequence will require that our grantees produce almost 300 Mb of finished sequence per year, starting in 1999. The goal is 99.9 percent accuracy with no gaps. It is estimated that NHGRI's sequence goal could be achieved with the expenditure of $60 million per year.
In preparation for fully scaling up the program by 1999, NHGRI began a pilot program in 1996 to test strategies and technologies designed for full-scale production sequencing. The pilot project program has been funded for almost half of its three-year duration. An administrative review of the progress at the end of the second year of funding will reveal more about the program's success, namely which, if any, of the approaches can achieve the increased sequencing rates needed. As the pilot projects have developed, it has become clear to NHGRI that there are two important factors that need to be addressed to develop the program to a level that can complete the human genome sequence. The first is how to accommodate a number of needs that are secondary to production per se, but are likely to be extremely important in increasing productivity over the long term, i.e., how to evaluate new technology at production levels, how to introduce new technology into production, how to address problem regions in DNA, how to provide an opportunity for new groups with promising approaches to attain production levels, and how to evaluate the quality of the DNA sequence produced. Another issue involves how to encourage interaction among the investigators involved in large-scale sequencing.
The competing renewal applications for the pilot projects, as well as for several other large-scale sequencing grants, will be due in a year. For the next competition, NHGRI proposes to implement a cooperative research network to address both the second-level needs and the need for increased communication. The proposed network would institutionalize a coordinated effort among the grantees in order to enhance the productivity of the groups as a whole, and thus increase the likelihood that the human sequence will be completed on time and within budget.
The RFA will call for applications for participation in a research network to be composed of three types of projects:
NHGRI would like to use the Cooperative Agreement (CA) mechanism to address these issues. If a CA mechanism is used, NHGRI proposes to organize a Steering Committee that will hold regular meetings to discuss progress and issues that arise during the course of completing the first human reference sequence. The membership of the Steering Committee will include the PIs of each of the grants and three external members, one of whom will chair the committee. There will also be one position on the Steering Committee for NHGRI staff, who will participate in the group process for setting research priorities, and implement any adjustment of research protocols or approaches warranted. Staff will retain the option to recommend to the NHGRI Director the readjustment or withholding of support from a project or the termination of the project. In addition to the Steering Committee, an Advisory Committee, composed of scientists who are not grantees under the CA, will be established to conduct an annual review of the entire program and review the advice put forward by the Steering Committee. This Advisory Committee will report to the Director, NHGRI.
In the ensuing discussion, Dr. Hood expressed concern about the need for 99.99 percent accuracy and the wisdom of pouring money into "gaps". If scientists must leave gaps, they should indicate how difficult the process was and orient the fragments. NHGRI's position is that we should at least try for no gaps. Dr. Hood indicated that there should be an upper limit of how much funding is expended on this goal. Specialized groups should be formed to target the difficult regions.
Dr. Cox expressed his approval of the establishment of a quality standard early in this project. However, he felt there was a cost accounting issue concerning the cost of technology development versus production. He felt a maximum of 10 percent should be spent on technology development. He was also concerned that it would cost more for specialized centers to do projects, than for main sequencing centers. These specialized centers must be carefully watched to be certain that they are adding value.
Dr. Peterson indicated that the general proposal had been submitted to the PIs and that the overall response had been favorable. Council indicated that they would endorse the project. NHGRI staff will go forward and seek NIH's approval to fund this program as a cooperative agreement.
Dr. Jordan called council's attention to a table developed by Jean Cahill and Joy Boyer on the number of women and minorities enrolled to participate in NHGRI grants. This table was developed to indicate to council to what extent NHGRI was in compliance with the NIH policy on the inclusion of women and minorities as subjects in clinical research. This policy requires that applications be reviewed to ensure that, as appropriate, each one meets the standard for inclusion of women and minorities. Those that fail to meet this standard are given an unacceptable gender or minority code, which results in an administrative bar-to-funding. These applications are given a second-level review in the closed session of the council meeting. If funding is likely, then the NHGRI staff works with the applicant to resolve compliance issues. Dr. Jordan indicated that the information would be reported to council once a year and asked if the council approved the table format. Clarification was given that the data represented only 12 ELSI grants that include human subjects. Council members found the term participants confusing and felt the table should be amended to include the descriptive phrase "human subjects." Dr. Duster indicated that the table needed a descriptive paragraph.
Dr. Jordan noted the items of interest, which are listed on the agenda.
Suggested agenda items for future meetings included having Dr. Richard Klausner, Director of the National Cancer Institute address the Council on areas of mutual interest. Dr. Collins has spoken with Dr. Klausner, who has expressed his willingness to address the Human Genome Advisory Council.
Dr. Chakravarti expressed his concerns in the informatics area. While information is becoming available on genotypes and maps, this information is frequently in an esoteric format that is not useful as a tool for researchers. This is a technology transfer question and maps and markers are not being used as they should be. Tools need to be written in simpler codes to make them more readily available to researchers. The problem is that genetic epidemiologists are not good programmers. There should be standardized tools available to all geneticists. This issue should be addressed by the Genetic Analysis Workshop meeting in Baltimore and perhaps at the National Epidemiology Meeting.
Dr. Nadeau indicated that we have inherited tools and ways of doing things that are historical. We need to re-evaluate how we do things and how we should be doing them in the future. He suggested this issue should be addressed in the next 5-year plan. Perspectives have changed and biologists should be consulted regarding their needs so databases can be reorganized.
The council indicated it was in favor of discussing this issue, but wanted to move cautiously and not start a new initiative. Council members wanted to wait and see what was decided at the Genetic Analysis Workshop in October.
The Council reviewed 117 applications, totaling $27,353,399. The applications included 16 regular research grants, five pilot projects, 24 ethics grants, 45 in response to request for application, two conference grants, one research career development award, 17 small business innovative research awards-phase I, two small business innovative research awards-phase II, two fellowship grants, and 1 R41. A total of 73 applications requesting $14,508,839 were recommended.
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Last Reviewed: April 2006