Department of Health and Human Services
Public Health Service
National Diabetes and Digestive and Kidney Diseases
Advisory Council
May 27-28, 1998
I. Call to Order
Dr. Gorden called to order the 147th NDDK Advisory Council meeting on May 27, 1998, at 8:40 a.m.
A. Attendance
Council Members Present (See Attachment A)
Dr. John Adamson (Ad hoc)
Dr. D. Montgomery Bissell, Jr.
Dr. Judith Bond
Dr. Richard J. Boxer
Dr. Jack E. Dixon
Dr. James R. Gavin, III
Dr. Gerhard Giebisch (Ad hoc)
Dr. David M. Harlan (Ex Officio)
Ms. Ruby R. Haughton
Ms. Genevieve Jackson
Dr. S. Robert Levine
Dr. Kristen McNutt
Dr. Eric G. Neilson
Dr. Daniel Podolsky
Dr. Barbara J. Rolls
Dr. Joseph T. Spence (Ex Officio)
Dr. Joseph H. Szurszewski
Dr. Richard D. Williams
Council Members Absent
Dr. Jerrold M. Olefsky
Dr. Barbara E. Hayes
Dr. Saulo Klahr
Dr. James Rothman
Dr. George Stamatoyannopoulos
B. Staff and Guests
In addition to Council members, others in attendance at the meeting included NIDDK staff members, NIH Office of the Director (OD), Center for Scientific Review (CSR) formally the Division of Research Grants (DRG), Scientific Review Administrators, and other NIH staff members. Guests were present during the open parts of the meeting. Attendees included the following:
| David Badman, NIDDK
Pamela Belton, NIDDK
Sharon Bourque, NIDDK
Josephine Briggs, NIDDK
Ben Burton, NIDDK (Emeritus)
Francisco Calvo, NIDDK
Dolph Chianchiano, National Kidney Foundation
Paul Coates, NIDDK
Florence Cohen, NIDDK
Catherine Cowie, NIDDK
Nancy B. Cummings, NIDDK
Leslie Curtis, NIDDK
Charlenia Daniels, NIDDK
Jane DeMouy, NIDDK
Nancy Dixon, NIDDK
Jacqueline Dobson, NIDDK
Richard Eastman, NIDDK
Linda Edgeman, NIDDK
Bill Elzinga, NIDDK
Gayla Elder-Leak, NIDDK
Jay Everhart, NIDDK
Richard Farishian, NIDDK
Ned Feder, NIDDK
Carol Feld, NIDDK
Bill Foster, NIDDK
Judith Fradkin, NIDDK
Joanne Gallivan, NIDDK
John Garthune, NIDDK
Sandy Garfield, NIDDK
Phillip Gorden, NIDDK
Colleen Guay-Broder, NIDDK
Ann Hagan, NIDDK
Frank Hamilton, NIDDK
Joan Harmon, NIDDK
Mary Harris, NIDDK
Maureen Harris, NIDDK
Barbara Harrison, NIDDK
Nancy Hazelton, OD, NIH
Trudy Hillard, NIDDK
Gladys Hirschman, NIDDK
Terri Holmes, NIDDK
Jay Hoofnagle, NIDDK
Karen Howard, NIDDK
Van S. Hubbard, NIDDK
Donna Huggins, NIDDK
Senil Iyengu, The Blue Sheet
Nikita James, NIDDK
Desiree Johnson, NIDDK
Ephraim Johnson, NIDDK
Valerie Johnson, NIDDK
Camille Jones, NIDDK
Kieran Kelley, NIDDK | M.A. Khan, CSR
Sooja Kim, CSR
Tom Kresina, NIDDK
Krish Krishman, CSR
John Kusek, NIDDK
L. Earl Laurence, NIDDK
Kim Law, NIDDK
Helen Ling, NIDDK
Billie Mackey, NIDDK
Denise Manouelian, NIDDK
Donita Marconi, NIDDK
Ronald Margolis, NIDDK
Winnie Martinez, NIDDK
Dan E. Matsumoto, NIDDK
Ken May, NIDDK
Ludlow McKay, NIDDK
Catherine McKeon, NIDDK
Lynn Morrison, American Gastroenterological Association
Clifford Moss, NIDDK
Neal Musto, NIDDKBeth Paterson, NIDDK
Denise Payne, NIDDK
Aretina Perry-Jones, NIDDK
Judith Podskalny, NIDDK
Rose Pruitt, NIDDK
Sharon Ricks, NIDDK
Jerry Roberts, National Human Growth Hormone Research Institute
Carmen Robinson, NIDDK
Alice Robinson, NIDDK
Charles Rodgers, NIDDK
Lakshmanan Sankaran, NIDDK
M. James Scherbenske, NIDDK
Bill Schmidt, Juvenile Diabetes Foundaton
Michael Showe, NIDDK
Elizabeth Singer, NIDDK
Philip F. Smith, NIDDK
Gloria Snowden, NIDDK
Lawrence Soler, Juvenile Diabetes Foundation
Walter Stolz, NIDDK
Joan Talley, NIDDK
Tommie S. Tralka, NIDDK
George Tucker, NIDDK
Robert Umek, NIDDK
Charles A. Wells, NIDDK
Nola Whitfield, NIDDK
Susan Yanovski, NIDDK
Rita Yeager, NIDDK
Charles Zellers, NIDDK |
C. Conflict of Interest Statement (See Attachment B)
Dr. Gorden called to the attention of the Council the Confidentiality and Conflict of Interest Statements. After discussing the scope of confidentiality and conflict of interest, he requested that Council members comply with the requirements. He reminded Council members to avoid a conflict of interest by leaving the room when the Council discussed individual applications in which an actual or perceived conflict of interest might occur. Members were asked to sign a statement to this effect. This did not apply to "en bloc" actions.
Dr. Gorden announced that the Council meeting would be open to the public in accordance with the provisions of Public Law 92-463 on Wednesday, May 27,1998, from 8:40 a.m. to 12:30 p.m., closed from 1:30 p.m. until 5:00 p.m., closed on Thursday, May 28, 1998, from 8:30 a.m. to 10:00 a.m. for review, Discussion, and evaluation of grant applications, and open from 11:00 a.m. to 12:00 p.m.
II. Consideration of the Summary Minutes of the Previous Meeting
The NDDK Advisory Council Summary Minutes of the last Council meeting were accepted unanimously by the Council members present.
III. Future Meeting Dates
Dr. Gorden asked for consideration of meeting dates for future NDDK Advisory Council meetings, and the following meeting dates were proposed and accepted:
September 14-15, 1998
February 17-18, 1999
June 16-17, 1999
September 8-9, 1999
February 2-3, 2000
May 31-June 1, 2000
September 20-21, 2000
IV. Director's Report
Dr. Gorden began his report by introducing two former members of the Council who were attending the present meeting in an ad hoc capacity: John Adamson, New York Blood Center, and Gerhard Giebisch, Yale University.
Dr. Gorden announced some recent changes in personnel at the NIH. He said that Dr. William Paul had left the Office of AIDS Research and Dr. Neal Nathanson was appointed to succeed him. He said Dr. James Battey had been appointed Director of the National Institute on Deafness and Communication Disorders, and Dr. Alan Graeff had been appointed the new Director of Center for Information Technology. In NIDDK, he reported that Drs. Maren Laughlin and Robert Umek had been appointed as Program Directors in the Division of Diabetes, Endocrinology, and Metabolic Diseases, and Dr. Neal Musto had been appointed as a Scientific Review Administrator in the Division of Extramural Activities . Dr. Gorden announced several awards that had been received by staff, Council members, and grantees.
Dr. Gorden gave a status report on the Budget for FY 1999 and announced that the President's Budget requested an 8.1 percent increase for the NIDDK over FY 1998 or a total of $944.3 million. He pointed out that the Council members were involved with the planning and implementation of all of the Institute's scientific initiatives and thus played an important role in determining how these funds were spent.
He described the plan for spending the additional monies the Institute had received for research on type 1 diabetes. He said that most of the funds would be used to support applications received in response to four Requests for Applications.
The Diabetes Working Group that had been congressionally authorized and chaired by Dr. C. Ronald Kahn, Director of the Joslin Clinic in Boston, had met to propose a blueprint for future diabetes research.
He said that the National Diabetes Education Program, begun 2 years ago, would be officially inaugurated in mid-June. He said that this program would take the messages of the Institute and make them more applicable to a wide-range of communities, particularly to the African-American and Hispanic Communities, the Pacific Islanders, and Native Americans.
Dr. Gorden summarized the Institute's Budget projections for the remainder of FY 1998 and said that there would not be sufficient funds to support all of the applications that were within the current payline of the Institute. He said that this was largely due to the funding of a number of special emphasis applications beyond the payline that had been highlighted by the Council at its February meeting. He indicated that the Institute did not plan to change its payline, but that it would delay the funding of some competing applications from July 1 to December 1 so that they could be funded from the FY 1999 Budget. He said that the specific applications would be selected so that no ongoing projects would be disrupted or delayed.
Discussion
Council members were concerned about the effect of funding the special emphasis grants on the rest of the grant program. Also, they asked about how the special emphasis grants were distributed across divisions. Dr. Gorden said that the special emphasis grants had been funded before it was clear that there would not be enough funds to support all the applications within the payline. He reminded the Council (1) that R29 grants were being enlarged and funded as R01s and (2) that the Institute had taken several steps to fund applications at levels closer to their recommended levels (i.e., with fewer administrative cuts) than previously. He also said that the Institute tried to equalize the special emphasis grants among the divisions.
Council members were concerned about delaying the funding of grants and asked how these delays could be justified. Also, concern was expressed that it be spread evenly among the programs.
Council members were concerned about the cap of $125,000 for reimbursement of salaries on grants and asked about the impact of this cap on planning. They pointed out that many thought the cap was too low for today’s economy. They asked if there were any plans to raise the cap. Dr. Gorden responded that he had not heard any Discussion about the pay cap or any plans to raise it.
A Council member asked about sending a negative message to the communities by funding to the 25th and 27th percentiles while Dr. Varmus said that the NIH was funding to the 30th percentile. Dr. Gorden responded that the figure that
Dr. Varmus had quoted was not a percentile payline but a success rate. He said that success rates included RFAs and special emphasis areas; and, when these were included, the NIDDK also had a success rate at least at the 30th percentile.
V. Reports and Discussions
A. Trans-NIH Programs in Genetics and Genomics
Dr. Catherine McKeon reported on various trans-NIH programs, especially in the areas of genetics and genomics. She began by discussing some of the ongoing programs that involved many institutes. As two examples she discussed the National Gene Vector Laboratories (NGVL) and the Center for Inherited Disease Research (CIDR). She also described initiatives for developing genomic resources for the rat and the zebrafish. She pointed out that the National Human Genome Research Institute planned to sequence the complete human genome in three steps: to map the genome, to make a physical map of the genome, and to sequence the physical map once it was made. She said that a lot of groups tried to shortcut the complete sequence and only focus on the expressed sequences since these were of more interest.
Dr. McKeon then described single nucleotide polymorphism (SNP) technology, emphasizing its importance in elucidating genetic variability within and across populations. She also indicated that SNPs will be important in mapping complex traits. She described the granting mechanisms that would be used to develop and utilize the SNP technology, and she said the NIH would develop an initiative to support the storage and analysis of data generated from SNPs.
She described other collaborative activities that were ongoing at the NIH such as NHANES epidemiology surveys, Clinical Research Curriculum Awards (K30), and the Human Frontiers Science Program.
Discussion
A Council member inquired about how the word was spread about the availability of these resources. Dr. McKeon responded that the resources were advertised in the "NIH Guide for Grants and Contracts" and other scientific publications, but that many investigators adopted a wait and see attitude when a new project was begun, so she said it would take time for it to become widely used.
Council members were concerned that the NIH was duplicating what could be done in private industry.
Dr. McKeon pointed out that industry was contributing to the database located at the NLM. Also, she said that the NGVL was a university-based system, and, as such, it would not have some of the patent problems encountered in private industry.
B. Follow-up on Career Award Program
Dr. Walter Stolz reported on the Career Award program, and gave an update on several of the "K" awards. He announced that the K01 award, designed for Ph.D.s, had been launched. He mentioned that the salary support available under the K02, which was formerly called the Research Career Development Award, had been increased. He reported that the salary support available under the K08 was increased to $65,000 for 1998 and to $75,000 for 1999. He said that K08 awardees needed more support in the later years of their award to be more competitive for an R01 award, and he described the small grants that would be available to the K08 holders during the 4th and 5th years of the awards. He said that current K08 award holders were being contacted about the program, and applications for the first small grants were expected October 1, 1998. He indicated that this program was in response to the assertion by Council members that K08 holders needed more help than was available currently in order to be competitive when applying for R01 awards.
He said that NIH had accepted the NIDDK Council members' recommendation for a career development award for training in patient-oriented research, and that NIH would now offer the K23 to meet that need. Dr. Stolz described the K24 as a new mid-career award for investigators already engaged in patient-oriented research. He said this award was for an individual in the first 15 years of his or her career and would give him or her up to half-time support for concentration on patient-oriented research.
Dr. Stolz indicated that the new K30 award was an institutional award for the development and implementation of curricula in clinical investigation.
Discussion
Council members expressed concern that the K01 award for the Ph.D. would eliminate many from submitting applications because of the requirement for 75 percent research effort. Dr. Stolz pointed out that the K01 was aimed at exactly those individuals who needed a concentrated, mentored research experience.
Council members expressed concern about the requirement that the K08 awardees could not receive Federal funds for 25 percent of their time. They pointed out that at year -06 if they rolled their K08 into an R01, they would have a large salary cut because they had not been able to diversify their research portfolio of grants. Also, they pointed out that these problems were not visible when they accepted the K08 award and only surfaced later. Dr. Stolz replied that they could be involved in other Federal grants, but could not draw salary from those grants until their K08 had ended because the K08 was designed to supply the entire salary for the PI's total professional effort.
Dr. Stolz said that he had presented the issue to the NIH, and that he had not been able to convince other extramural officials of the Council's position, but he offered to raise the issue again.
Council members expressed concern about the tracking of new people applying for R01 awards given the demise of the R29 awards. Dr. Stolz assured the Council members that new applicants for R01 awards would be tracked. He said that whether the new R01 applicants would be given additional consideration as the R29 applicants had been given was an issue that had not been settled.
Council members suggested several ways to encourage new investigators to apply for R01s such as being helped to pay off debt incurred in obtaining their degrees. They pointed out that once potential physician-investigators became part of an HMO to pay off their debt, they were lost to research. They said the half-life of a physician-investigator was about 4.9 years, and it was suggested that educational loans could be amortized over a number of years to encourage the investigators to stay in research.
Dr. Gorden said that tying the repayment of educational loans to receiving grants would be a legislative issue requiring a legislative solution.
C. Annual Report on the Division of Intramural Research
Dr. Allen Spiegel gave the Intramural Division report, and began by announcing awards and key personnel changes over the past year. He said that several senior people had departed, and he described some of the recruiting measures that were underway.
Dr. Spiegel described the Board of Scientific Counselors and discussed some of the results of their reviews. He described the tenure reviews and pointed out that the Board reviewed the applicants as part of the tenure process.
Dr. Spiegel described a cooperative initiative between the Division for Intramural Research and the Walter Reed Army Medical Center regarding research on kidney and pancreatic islet cell transplantation. He pointed out that this initiative offered exciting research that could benefit patients in two programmatic areas of interest to NIDDK. He said that there was a critical mass of expertise at the NIH, both in NIDDK and other institutes, as well as at the Walter Reed Army Medical Center that would make this initiative timely. He also pointed out that the Clinical Center lent itself to small innovative clinical trials.
VI. Scientific Presentation: ICC and CO: A New Pacemaker and a New Transmitter in the GI Tract
Dr. Joseph Szurszewski gave the scientific presentation. He began by describing the interstitial cells of Cajal (ICCs). He said that carbon monoxide (CO) was the signaling molecule between ICCs and the smooth muscle cells that line the walls of the gut. He gave examples of why the work was important, and he showed that a deficit in the interstitial network and/or an absence of voltage dependent ionic currents in interstitial cells might account for intestinal obstruction and severe chronic constipation present in some people.
He described what is known about the electrical system in the normal gut and the involvement of ICCs. He said that their role could be considered analogous to the sinoatrial node in the Purkinje fiber conducting system of the heart. He said that the pacemaking activity would be analogous. He presented two hypotheses to explain the signal that passes from the ICCs to the smooth muscle cells. The first hypothesis was that the ICCs generated a pacemaking current which gave rise to a slow wave activity that spread passively to the smooth muscle fibers. The second hypothesis was that ICCs released a chemical mediator that influenced the channels that conducted currents in the smooth muscle cells. He described the evidence supporting the second hypothesis and said that they only had found the enzyme, heme oxygenase-2, and that this enzyme forms CO. He pointed out that the CO produced in ICCs could influence the electrical activity of smooth muscle cells in the circular muscle layer. He reported what happens when this system does not work properly and the impact on patients.
Discussion
A Council member asked about ICCs' access to heme.
Dr. Szurszewski responded that heme protein was available and that heme protein gave rise to catalyst products such as CO. He said that heme oxygenase-2 was very profuse in nerve fibers in smooth muscle. A Council member pointed out that heme oxygenase activity in the intestinal mucosa was greater than in the ICCs and was a major source of CO. He asked how this affected motility. Dr. Szurszewski responded that the small bowel muscle layer seemed to generate more CO than any other place in the body.
A Council member asked if he had studied heme oxygenase-2 knock-out mice for abnormalities in testicular sperm.
Dr. Szurszewski responded that they had not, but had noted that these animals had erections, but could not ejaculate. He said that they had not studied the effects of psychotrophic medications and narcotics on these cells.
VII. Division Director's Reports
A. Division of Diabetes, Endocrinology, and Metabolic Diseases
Dr. Eastman began the Division report by pointing out that diabetes had received significant attention over the past year both within the Institute and outside of it, and he asked Dr. Joan Harmon to give an update on the diabetes activities.
Dr. Harmon reviewed the status of diabetes initiatives that had grown out of the Presidential interest in prevention and cure of type 1 diabetes and how the $150 million in special funds would be spent over the 5-year period. She pointed out that there had been several groups that had met to design activities and processes to respond to this initiative. The results included seven RFAs, two major meetings (one in September 1997 and another in October 1997), and several planned workshops. She described cooperative efforts with other institutes that were to be pursued, such as using mouse models to develop prevention therapies and to develop an expressed sequence database. She said that an emphasis would be placed on developing clinically applicable technologies.
B. Division of Digestive Diseases and Nutrition
Dr. Hoofnagle began the Division report by describing initiatives for FY 1999, which included three on obesity (a clinical trial and initiatives on prevention of obesity and the molecular basis of obesity). Topics for other initiatives included GI motility and the enteric nervous system, hemochromatosis, celiac disease, inflammatory bowel disease, and hepatitis C. He said that program announcements were planned on the prevention and recurrence of disease after liver transplantation, liver disease in women and minority populations, and small grants for clinical trials and epidemiologic studies focusing on hepatitis C.
Dr. Hoofnagle gave an update on hepatitis C, pointing out that it contributed to one-third of the cases of chronic liver disease in the U.S. and is the single most common reason for liver transplantation. He said that it was estimated that four million Americans were infected with hepatitis C, with the majority of them unaware that they had the disease. He described some of the planned activities to address this disease which included expansion of the NIDDK Intramural Program and co-funding with CDC of a national surveillance system for chronic liver disease.
C. Division of Kidney, Urologic, and Hematologic Diseases
Dr. Briggs gave the Division report, and began by describing potential initiatives for the next fiscal year. She described the lack of information on genetic factors that cause susceptibility to end-stage renal disease and outlined activities, techniques and workshops planned to address these issues. She described a workshop focusing on dialysis patients and their problems with vascular access and nutrition. Another initiative was in hemochromotosis and iron transport and she said there were plans to strengthen these programs. A third initiative was in urinary incontinence and she pointed out that there was a need for clinical work in this area.
Dr. Briggs gave an update on the trans-NIH zebrafish project. She pointed out that the purpose was not to describe the complete genome in the zebrafish, but to sequence the expressed genes. She described a number of ways that the zebrafish could be used to elucidate molecular events.
Discussion
A Council member asked about the nutritional assessment of diabetics on dialysis and if Dr. Briggs might use the high mortality in diabetic patients from coronary disease as an end point to evaluate the effects of nutritional state and supplementation with Vitamins E and C and other antioxidants in this population.
Dr. Briggs responded that there was an increased cardiovascular mortality in end-stage renal disease patients and that the diabetic patients were the subgroup at greatest risk. She said that the role of antioxidants was only one part of the nutritional picture, but that cardiovascular events were a huge problem in the end-stage renal disease and diabetic patients.
VIII. Consideration of Review of Grant Applications
Summary Table 1
| Applications Taken to Council by Budget Category |
| Budget Category | Scored Applications | NRFC Applications | Deferred Applications | No Action | Total Applications |
| Regulary Research * (P01, R01, R29, R37, R43, R44) | 671 | - | - | - | 671 |
| Other Research * (R03, R13, R15, R21, K08) | 131 | - | - | - | 131 |
| Centers (P50) | 18 | - | - | - | 18 |
| Training * (T32) | 21 | - | - | - | 21 |
| MBS (S06) ^ DK Secondary only | - | - | - | - | - |
| Totals | 841 | - | - | - | 841 |
* Includes both DK primary and secondary
^ Minority Biomedical Support Program. (This program is administered by the NIGMS but jointly funded by other ICD's. The Council concurred with NIDDK recommendations for scoring these grant applications.)
Of these applications, three were received from institutions outside the U.S.A.
Summary Table 2
| Applications Taken to Council by Support Mechanism |
| Support Mechanism | Scored Applications | NRFC Applications | Deferred Applications | No Action | Total Applications |
| Program Projects (P01) | 7 | - | - | - | 7 |
| Research (R01) | 522 | - | - | - | 522 |
| FIRST Awards (R29) | 40 | - | - | - | 40 |
| MERIT Awards (R37) | 3 | - | - | - | 3 |
| STTR (R41) (R42) | 11 1 | - - | - - | - - | 11 1 |
| SBIR (R43) (R44) | 64 23 | - - | - - | - - | 64 23 |
| Small Grants (R03) | 23 | - | - | - | 23 |
| Conferences (R13) | 52 | - | - | - | 52 |
| AREA (R15) | 14 | - | - | - | 14 |
| Exploratory/Developmental (R21) | 12 | - | - | - | 12 |
| Careers (K08) | 30 | - | - | - | 30 |
| Special Centers (P50) | 18 | - | - | - | 18 |
| Training (T32) | 21 | - | - | - | 21 |
| MBS (S06) * | - | - | - | - | - |
| Totals | 841 | - | - | - | 841 |
* Minority Biomedical Support Program
Council did not concur with IRG recommendations on 13 applications.
Summary Table 3
| Applications Not Taken to Council |
| Categories by Support Mechanism | Bottom-Tier Applications | NRFC Applications | Excluded by Institute Staff | Non-Comp | Total Applications |
| Traditional Research (R01) | 8 | 2 | - | 303 | 313 |
| FIRST Awards (R29) | - | 1 | - | 54 | 55 |
| STTR Phase I (R41) | - | - | - |
| 11 |
| SBIR Phase I (R43) | - | 1 | - | 60 | 61 |
| SBIR Phase II (R44) | - | - | - | 7 | 7 |
| Small Grants (R03) | - | 1 | - | - | 1 |
| AREA Grants (R15) | - | - | - | 7 | 7 |
| CIA (K08) | - | 3 | - | - | 3 |
| Special Centers (P50) | - | - | - | 1 | 1 |
| Exploratory/Developmental (R21) | - | - | - | 5 | 5 |
| Totals | 8 | 8 | - | 448 | 464 |
IX. Adjournment
Dr. Gorden thanked the Council members for their attendance and advice. There being no other business, Dr. Gorden adjourned the 147th meeting of the NDDK Advisory Council on May 28, 1998, at 12:05 p.m.
I hereby certify that, to the best of my knowledge, the foregoing summary minutes and attachments are accurate and complete.
Phillip Gorden, M.D.
Director, National Institute of Diabetes and
Digestive and Kidney Diseases
and
Chairman, National Diabetes and Digestive and
Kidney Diseases Advisory Council
