Liver and Biliary Disease Research Supported by the National Institutes of Health

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1 Special Article Liver and Biliary Disease Research Supported by the National Institutes of Health THOMAS F. KRESINA The National Institutes of Health (NIH) is the major Fed- and biliary disease research are the National Institute on eral agency supporting both biomedical research and training Alcohol Abuse and Alcoholism (NIAAA), which supports in the digestive diseases. Among the Institutes of the NIH, alcohol-related liver studies, and the National Institute of the National Institute of Diabetes and Digestive and Kidney Environmental Health Sciences (NIEHS), which supports he- Diseases (NIDDK) provides the largest share of funding in patic toxicology research. These five institutes NIDDK, digestive diseases and specifically in liver diseases. The pres- NCI, NIAID, NIAAA, and NIEHS provide almost 90% of ent article summarizes the Liver and Biliary Diseases Re- the research dollars for NIH-supported liver research. Fundsearch Program of NIDDK as well as liver and biliary disease ing by these institutes over the past 5 years has increased, related research supported by other Institutes and Centers though by differing increments. Data from the Veterans Adof the NIH. The period covered in this review is fiscal years ministration are provided for comparison (Fig. 2) to present. Data for 1987 through 1994 are from the Liver and Biliary Disease Related Research of the NIDDK. The NIH Data Book 1 and the Extramural Trends and Data Book. 2 NIDDK is comprised of six divisions, one intramural (located For fiscal years 1995 through 1997, the data are from NIH on the campus of the NIH) and five extramural (off-campus). Institutes. The Extramural Trends and Data Book can now Extramural are the Division of Kidney, Urologic, and Hemabe accessed by the internet through the NIH home page. The tologic Diseases (DKUHD); the Division of Diabetes, Endobook s direct address to the preface, which opens the table crinology, and Metabolic Diseases (DDEMD); the Division of contents, is: of Digestive Diseases and Nutrition (DDDN); Division of PREFACE.HTM. Extramural Activities (DEA); and Division of Nutrition Coor- Table 1 provides a listing of grant mechanisms used by dination (DNC). These administer their designated programs the NIH. and work within a distribution of funds to the NIDDK extramural program. The total NIDDK budget for fiscal years 1992 LIVER AND BILIARY DISEASE RELATED through 1996 and the estimated budgets for 1997 and 1998 RESEARCH OF NIH are presented in Table 3. From 1992 through 1996, the Liver and biliary disease related research is supported by NIDDK budget increased by 16.2%, from $661.4 million to 13 Institutes and Centers of the NIH (Table 2). The level of $768.4 million. The success rate for grant applications refunding in fiscal year (FY) 1996 was approximately $185.6 ferred to NIDDK increased in parallel from 20% in 1993 to million, with the largest fraction (28.1% of the total) coming 26% in In FY 1996, 2,249 research project grants were from NIDDK. The multiple research programs for the liver funded by NIDDK; for 1997 and 1998, the projections are and biliary area in NIDDK are shown in Fig. 1. The majority 2,352 and 2,389 awards, respectively. are administered by the Division of Digestive Diseases and Expenditures by NIDDK for liver and biliary disease re- Nutrition (DDDN); within DDDN, they are assigned to the lated research have represented 6.1 to 6.4% of the Institute s Liver and Biliary Program, the Clinical Trials Program, or the total budget. Between 1992 and 1996, this funding increased Digestive Diseases Centers Program (Fig. 1). The National 13%, from $41.8 million to $47.3 million. Of the total, the Cancer Institute (NCI) and the National Institute of Allergy largest fraction comes from the Liver and Biliary Disease and Infectious Diseases (NIAID) also support substantial Program of DDDN (Dr. Thomas Kresina, Program Director), liver and biliary disease related research, representing 24.6% accounting for approximately 50%. The remainder is proand 17.6% of the total, respectively. The research portfolio vided by the Clinical Trials Program of DDDN (Tommie of the NCI focuses on hepatocellular carcinoma and the car- Sue Tralka, Program Director), the Digestive Diseases Center cinogenic potential of viral infections and toxins. The liver Program (Dr. Judith Podskalny, Program Director), the intraand biliary disease portfolio of the NIAID primarily supports mural program, which includes the Liver Diseases Section investigations of immunological and infectious diseases of (Dr. Jake Liang, Chief), and funding for liver and biliary the liver. Two other institutes adding further depth to liver disease related research within other divisions of the NIDDK, encompassing projects with liver-research components but in the context of other organ-system diseases such From the Division of Digestive Diseases and Nutrition, National Institute of Diabetes as nephritis and diabetes. DKUHD and DDEMD support 58 and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD. grants with a liver component at a total cost of $12.7 million. Received July 15, 1997; accepted September 1, The Digestive Diseases Centers Program funds shared re- Address reprint requests to: Thomas F. Kresina, Ph.D., Room 6AN-12A, Building sources, or core facilities, that foster interdisciplinary re- 45, DDDN, NIDDK, NIH, Bethesda, MD Fax: (301) This is a US government work. There are no restrictions on its use. search among established investigators in digestive diseases /97/ $0.00/0 Among the 12 currently active centers, liver disease is the 1355

2 1356 KRESINA HEPATOLOGY November 1997 TABLE 1. NIH Grant Mechanisms R01 Investigator-initiated grant-in-aid (regular research project grant) R03 Small grant award (varies by Institute NIDDK provides $50,000 per year for 2 years) R15 Academic Research Enhancement Award (AREA) award (undergraduate teaching institutions) R29 First Independent Research Support and Transition (FIRST) award (for newly independent young investigator) R37 MERIT award (senior investigator award) R44/45 Small Business Innovation Research (SBIR) Grant S06 Minority Biomedical Research Support (research and training at minority institutions) P01 Program project (multiproject grant with a major or basic theme) P50 Specialized Center grant K series Training and Career awards F series Fellowship awards T series Training grants U series Cooperative agreements (interactive grant between NIH staff and PI) N01 Federal research and development contract FIG. 1. The Institutes of NIH and Subdivisions of NIDDK that support major amounts of liver research. primary focus in 4 and a subtheme in the majority. The Program budget for FY 1996 was $9.8 million, of which the Clinical Trials Program provided a total of $5.6 million approximately 50% supported liver and biliary-related re- in funding for liver and biliary disease research. search. An additional DDDN program for liver and biliary disease The Digestive Diseases Clinical Trials Program currently research is the Small Business Innovation Research (SBIR) funds 11 major clinical trials or epidemiological studies as Program (Dr. Judith M. Podskalny, Director). It has ear- R01 grants, of which 6 deal primarily with liver disease. The marked funds to promote technical innovation within the latter include the natural history of cholestatic liver disease, American small-business community. It is an effort by Con- emergency portocaval shunting for variceal hemorrhage, preof federally funded research. In FY 1996, the program sup- gress to involve the private sector in the commercialization vention of portal hypertension using b-blockers, use of transported seven projects at the level of $1,150,000. jugular intrahepatic portal systemic shunt stents for variceal hemorrhage and for intractable ascites, and therapy of priencompasses basic and clinical research on both the normal The portfolio of the Liver and Biliary Diseases Program mary biliary cirrhosis with methotrexate. The Clinical Trials Program also funds small pilot (R03) grants, which investigaareas of basic research include: liver growth and repair, gene function and the diseases of the liver and biliary tract. The tors may use to prepare applications for clinical trials or to carry out small pilot studies. Clinical trials may be funded therapy, liver cell injury, bile formation and biliary physiol- also as Cooperative Agreements or Contracts. For FY 1996, ogy, and basic and applied projects on liver transplantation including studies of preservation and storage. The diseaseoriented research includes pathogenesis of chronic hepatitis TABLE 2. Funding of Liver and Liver-Related Activities of the NIH and its complications, gallstones, autoimmune liver disease, and genetic diseases. Five grant mechanisms are utilized by Institute, Center, FY 96 Extramural the Program: the investigator-initiated project (R01), the or Office (in $1,000s) % of Total FY 96 FIRST award (R29), the small grant award (R03), the MERIT NIA 1, ,985 award (R37), and program projects (P01). The funding level NIAAA 14, ,772 for fiscal years 1992 through 1996 is presented in Table 3 NIAID 29, ,448 and the support by grant mechanism in Table 4. Although NCI 41, ,502 the level of support during this 4-year period rose by 4.7%, NICHD 3, ,081 from $25.3 million to $26.5 million, as a percentage of the NIDDK 47, ,236 NIDA overall NIDDK budget it declined from 3.8% to 3.4%. The NIEHS 14, ,700 nadir was in FY 1995, at 3.1%; this reflected a decrease in NIGMS 4, ,284 funding of R01 grants to 75 awards, compared with an aver- NIMH age of 88 in other years. This drop was caused by a large NHLBI 5,549 (22,525) 3.2 5,549 (22,525) number of competing renewal proposals and a relatively low NINDS success rate for R01 applications overall in FY In 1996, NCRR 5, ,035 the success rate rebounded with funding of 90 grants (Table NINR ). Total: $185,600 The titles and abstracts of currently active grants can be NOTE. Data taken from the report of the DDICC. The data in parentheses grouped to provide an unofficial profile of the scientific areas for the NHLBI are the newly reported value for liver disease research and supported by the Program. For FY 1996, cholestasis/bile are included in the total support value. acids was the area with the largest number of grants and

3 HEPATOLOGY Vol. 26, No. 5, 1997 KRESINA 1357 TABLE 4. Number of Awards and Research Dollars Supported by the NIDDK Liver and Biliary Diseases Program Number of Awards (support in millions of $) Fiscal Year R01 R29 R ($17.7) 21 ($2.1) 8 ($3.6) ($18.1) 19 ($2.1) 8 ($3.7) ($18.1) 18 ($1.9) 9 ($4.2) ($16.3) 20 ($2.1) 8 ($3.7) ($20.3) 21 ($2.3) 7 ($2.7) research. Perhaps the most successful mechanism is the RFA or PA, which is prepared by the program staff of NIDDK. These arise usually in response to advisory groups or through communication from the community of researchers or lay groups. They are published in the NIH Guide for Grants and Contracts, advertised on the NIH homepage ( and distributed at meetings. RFAs and PAs differ in that an RFA has a single application receipt date, an ad hoc (special) initial review group, and earmarked funds. By contrast, a PA generally is active for a full fiscal year, is evaluated by the standard chartered review groups, and does FIG. 2. Liver research support for FY 1990 through ( ) NIDDK; not have earmarked funds. Although applications submitted ( ) NCI; ( ) NIAID; ( ) NIEHS; ( ) NIAAS; and ( ) VA. in response to a PA compete directly with regular research proposals in study sections, they receive special consideration for funding through secondary review by the Institute, dollar support; second was liver cell biology and transport. National Advisory Council, and program staff. Together, these areas accounted for approximately 50% of Generally, a NIDDK initiative will be discussed with prothe awards and funding in the Program. Other areas of em- gram staff of other institutes, often at the Digestive Diseases phasis are noted in Table 5. The number of awards and Interagency Coordinating Committee or the NIDDK Adviamounts of funding are determined largely by peer review, sory Council. It is prepared as a program concept by Institute a process whereby new and competing proposals undergo staff and presented to the NIDDK Advisory Subcouncil for evaluation and prioritization by initial review groups (study the Division of Digestive Diseases and Nutrition for advice sections) of the NIH. Research in viral hepatitis and in cancer and clearance. On approval, the RFA or PA is administraare not represented, as these are part of the mission of NIAID tively processed for incorporation into the Institute s budget and NCI, respectively. plan. RFAs may increase the numbers of grants funded, but Several mechanisms, which are broadly referred to as because they have a monetary set-aside, they may reduce the planned initiatives, are used to expand and vitalize research pay line of regularly submitted grant applications. The pay in specific areas. These include the Request for Applications line is the cutoff for funding of approved applications, ranked (RFA) and Program Announcement (PA). Initiatives can also by percentile, in a given review cycle. In past years, the pay take the form of a workshop or symposium, or development of a contract or cooperative agreement in a specific area of TABLE 3. Liver and Biliary Research Funding as a Percentage of the NIDDK Budget line has varied from as low as the 14th percentile to as high as the 27th. In fiscal years when the pay line is below the 20th percentile, proposed initiatives and particularly RFAs may not be launched, as they can have the effect of further reducing the funding of investigator-initiated R01 applica- NIDDK Liver and Liver and Biliary NIDDK Budget Related Research* Disease Program Fiscal Year (in millions $) (%) (%) TABLE 5. Focused Research Areas of the Liver and Biliary Disease Program, FY (6.3) 25.3 (3.8) Number Funding (6.3) 25.6 (3.8) Area of Awards (% of total) (6.4) 26.2 (3.7) (6.1) 23.1 (3.1) Cholestasis and bile acids 32 $7,972,000 (30%) (6.2) 26.5 (3.4) Liver biology and transport 30 $5,538,000 (21%) 1997 (appropriation) Genetic liver disease 8 $1,802,000 (7%) 1998 (budget proposal) Liver fibrosis and necrosis 11 $2,285,000 (9%) Transplantation and immunology 22 $4,431,000 (17%) * Total expenditures by the NIDDK for liver research and liver-related Liver regeneration 11 $1,382,000 (5%) research. Gene therapy and hepatocyte engineering 9 $1,612,000 (6%) The Liver and Biliary Program is restricted to regular research projects Gallstones 9 $1,216,000 (5%) that comprise the following grant mechanisms: the investigator-initiated Liver toxicity 1 $251,000 (1%) R01 grant, the FIRST (R29) award, the small grant (R03) award, merit (R37) Total: 130 $26,480,000 awards, and program projects (P01). tions.

4 1358 KRESINA HEPATOLOGY November 1997 The Liver and Biliary Diseases Program has published sis, polio virus (vaccine vector), hepatic adenovirus, and hepatitis seven initiatives over the last 6 fiscal years. In 1993, a PA A, B, C, D, and E. In FY 1996 and 1997, the Institute was announced for isolating the genes for Wilson s disease sponsored an RFA for multidisciplinary centers for hepatitis and hemochromatosis. In 1995, a PA entitled Stent Patency C research. Four centers were awarded, one in collaboration and Stenosis in TIPS was developed from recommendations with NIDDK and the Office for Minority Health Research. of the National Digestive Diseases Advisory Board, to encourage These focus on hepatitis C virology, epidemiology, immunol- research on the biology of stent patency and stenosis. It ogy, and vaccine development. Collaborative effort between complemented a PA from the Clinical Trials Program on the NIAID and NIDDK continues with the currently active use of TIPS in portal hypertension. Also in 1995, a PA was Program Announcement Enteric and Hepatic Infectious Diseases published jointly with the Gastrointestinal Mucosal Immunology (PA97-053). Program (Dr. Frank Hamilton, Director) on autoim- Liver and Biliary Disease Related Research of the NIAAA. The mune digestive diseases including autoimmune hepatitis, primary NIAAA supports 74 extramural research projects at $14.8 biliary cirrhosis, and primary sclerosing cholangitis and million. The major subject areas include mechanisms of in- inflammatory bowel disease. In 1996, a PA was announced flammation and fibrogenesis, alcohol and intermediary me- offering seed money for digestive disease related pilot tabolism in the liver, free radical formation, genetic regulation projects (R03 grants) within currently funded international of alcohol metabolism and of collagen, effects of alcohol NIAID center grants. This initiative, which is currently active, on hepatocellular transport, membranes, subcellular organelles seeks to expand international collaborations in digestive and and proliferation, progression and complications of alseeks infectious diseases that have unique clinical aspects. Other coholic liver disease, and treatment including transplantation. currently active initiatives and announcements in liver and biliary disease research include PAs to support studies of Liver and Biliary Disease Related Research of the NIEHS. The pediatric liver disease (PA ), hepatic and biliary stem NIEHS supports 84 extramural research projects ($12.7 mil- cells (PA ), and enteric and hepatic infectious diseases lion) as regular research projects, centers, and superfund (PA ). These last three PAs are currently active and grants. The latter are multiproject awards on biological prerequest investigator-initiated R01, R29, and R03 applications. dictors of exposure to environmental toxins, toxic metal contamination, Individuals interested in submitting applications are encouraged and risk assessment for chemical toxins. The to contact NIH program staff for additional information. liver-related research focuses on drug metabolism, hepatotoxicity, Liver and Biliary Disease Related Research of the NCI. The and environmental factors in liver cancer. NCI provides approximately $41.4 million for liver and bili- Liver and Liver-Related Research of the NCRR and NHLBI. The ary related research, a level of funding that is second only NCRR supports 73 extramural grants at $5.035 million, the to that from NIDDK. The number of awards is divided almost majority of which goes to General Clinical Research Centers equally between research project grants (138 grants at $26.7 with a hepatobiliary component. Other specialized awards million) and cooperative agreements (129 grants at $8.2 mil- are for imaging resource centers and regional primate facilities. lion). The latter are large multiproject, multidisciplinary programs One research project is on the pathogenesis of mouse with a common theme or goal such as liver cancer. hepatitis virus infection. The National Heart Lung and Blood Cooperative Agreements require a substantial effort from Institute Institute funds 22 liver and biliary disease related projects, staff to facilitate and monitor the research activities. which it valued at $5.4 million in its report to the DDICC, The subject areas of the Liver Cancer Grant Portfolio but at $ to the Office of Financial Management (Table include liver cell growth, genetics and pathogenesis of liver 2). The latter is the official level of liver research support for cancer, carcinogenesis, liver cell metabolism and extracellular the institute. NHLBI funds R01 grants as well as program matrix, markers of hepatocellular carcinoma, imaging, projects, centers, cooperative agreements, and contracts. and surgical and medical therapy of liver cancer. Themes Eighteen of these are research-project grants involving stud- supported in cooperative agreements include chemopreven- ies of ischemia-reperfusion injury, hepatic sterol and lipoprotein tion of cancer and identification of intermediate markers of metabolism, and protease inhibitors. A single Specialized cancer risk; nutritional topics such as generation of carcino- Center of Research (SCOR) grant is focused on hepatic lipoprotein gens in the cooking process and the use of nutrition in chemoprevention; metabolism and atherogenesis. A cooperative agreegens diagnostic imaging of tumors; the biology of ment, multicenter study deals with diet and lipoproteins in normal versus tumor cells; the epidemiology of hepatocellular coronary heart disease. A large contract deals with the natural carcinoma; tumorigenesis, oncogenes and the genetics of history of posttransfusion hepatitis. liver cancer; and therapy of liver cancer. Specialized grants Liver and Biliary Disease Related Research of the NICHD and deal with development of anticancer compounds including NIGMS. The National Institute of Child Health and Development nucleoside analogues, leucovorin, fluoropyrimidines, metallothioneins, (NICHD) supports 18 extramural research projects at quinones, and phenols. $3.081 million (14 research projects, 2 research centers, 1 Liver and Biliary Disease Related Research of the NIAID. The institutional training grant, and 1 contract). The investigatorpurview of the NIAID includes viral hepatitis, other hepatic initiated R01 grants have specific aims related to liver function infectious diseases, and the immunology of liver transplantation. or metabolism during ontogeny and neonatal jaundice. The institute therefore has a substantial portfolio of The program projects have components related to the gene liver and biliary disease related research with 95 extramural therapy of liver disease; the hormonal regulation of neonatal projects supported at $23.5 million (80 research project hepatocyte differentiation; and liver-derived growth factors grants, 2 research centers, 4 career awards, 1 institutional in lactation. The single contract is a clinical study of hyperbil- training grant, 3 fellowship awards, and 4 contracts). By irubinemia in newborns. infectious pathogen, the awards are for hepatic schistosomiasis, The National Institute of General Medical Sciences hydatidosis, amebiasis, cryptosporidium, trypanosomia- (NIGMS) supports 50 liver and biliary disease related re-

5 HEPATOLOGY Vol. 26, No. 5, 1997 KRESINA 1359 TABLE 6. Support of Liver and Biliary Research by Funding differences emerge. NCI and NIAID favor clinical cooperative Mechanism, FY 1996 agreements, while NIDDK supports a relatively large number Funding Mechanism NCI NIDDK NIAID NIAAA NIEHS of young investigators with R29 or FIRST awards. NIAAA provides a substantial number of R37 (MERIT) awards to Research Project Grants senior researchers in the liver area. The NIEHS supports a R comparatively large number of Federal contracts. R R THE FUTURE: THE FY 1998 BUDGET P Research Center * The next fiscal year for the Federal government begins Career Awards October 1, The budget process began in February, Training Awards , when the President sent his request for FY 1998 to Fellowship Awards Congress, including an appropriation of $ million for Contracts the NIH. This represents a 2.6% increase (or $337 million) Cooperative Agreements over FY 1997 and continues an emphasis on the research Cooperative Agreements, Clinical project grant, with approximately 57% of the total for this * Includes 10 superfund Research and Development sites. type of award. If approved, 26,679 investigator-initiated projects could be funded, of which 7,112 would be new or competing grants, an increase of 3.9% over FY For FY 1998, the NIH director, in consultation with the search projects including 48 regular research grants ($3.6 Institutes and Centers, has identified areas for special emphamillion) and 2 center grants ($0.6 million). The regular re- sis that will be supported by a monetary set-aside, to allow search projects are predominantly R01 awards that focus on for funding beyond that available with the established approliver physiology and metabolism as well as gene expression priations to the Institutes and Centers. The areas are as foland regulation. In general, NIGMS funds basic physiology lows: and metabolism rather than specific diseases or pathology. 1. Therapeutics and Drug Development ($40 million), with The Institute supports a limited number of R29 grants on emphasis on new drug development in cancer, studies of prognostic factors for clinical trials, cryobiology of hepato- drug and alcohol addiction, new interventions in infectious cytes, and the response of the liver to sepsis and injury. Small diseases, new treatments for sensory disorders and mental minority (S06) grants focus on cytoskeletal structure and illness, new methods in the bioengineering of tissue repair, gene regulation in hepatocytes. and improved care at the end of life. Liver and Biliary Disease Related Research of NINDS and 2. Biology of the Brain ($36.7 million), with emphasis in NIMH. The National Institute of Neurological Diseases and the fields of molecular genetics, imaging cell biology and Stroke (NINDS) supports few liver-related projects. A sub- cell signaling, with expanded activity in neural development, project of a program project investigates the role of the liver neurodegeneration, the biological basis of autism, physiology as a reservoir of macrophages, in abnormalities and complica- of pain, traumatic injury to the brain, and the use of mouse tions that follow brain trauma. The National Institute of Men- models to study addiction behavior and the regulation of tal Health supports a career award (K05) with a multiorgan weight and appetite. focus on postingestive conditioning of appetite by carbohy- 3. New Approaches to Pathogenesis ($34.6 million), with drates including an assessment of the nutritive uncondi- emphasis on new insight into genes, proteins, and cells tioned stimulus in the liver. related to disease processes such as animal models of carci- Liver and Biliary Disease Related Research of the NIA and nogenesis, using new informational integration methods NIDA. The National Institute of Aging supports 12 extramu- to study complex biological processes, applying new and ral awards for liver research, of which 10 are research projects diverse methods to the study of osteoarthritis, birth defects, (six R01s, one R37, one R03, two R29 awards); 2 are training growth disorders, and infections of the liver, lung, and (K08) awards. Major areas of study include the effect of gastrointestinal tract. aging on hepatocellular synthetic processes and intermediary 4. New Preventive Strategies Against Disease ($51.1 milmetabolism, mitochondrial function, oxidant protection, lion), with emphasis on novel approaches to disease prevendrug metabolism, hepatotoxicity, and cell death. The Na- tion using both animal models and human disease, and tartional Institute of Drug Abuse supports research on the he- geting cancer, diabetes mellitus, cerebral palsy, asthma, patic effects of illicit drugs. alcohol abuse, and drug abuse; vaccine development for infectious agents such as human immunodeficiency virus as NIH SUPPORT FOR LIVER AND BILIARY DISEASE well as new and resurgent infections; and training of health RELATED RESEARCH: SUMMARY care professionals on new genetic information that can be Thirteen institutes and centers of the NIH provide funding used to prevent disease. for liver-related research. Although the portfolio for each is 5. Genetic Medicine ($40.9 million), with an emphasis on unique, more than 50% of the dollar support comes from methods for efficient genetic analysis and distribution of gene NIDDK, NCI, and NIAID. When NIAAA and NIEHS are maps and sequences; definition of genetic damage in cancer added, almost 90% of the liver and biliary disease related cells; identification of inherited mutations that contribute to support reported to the DDICC is accounted for. This fund- cancer risk; developmental abnormalities, immunodeficiencies, ing is presented by the grant mechanism shown in Table 6. mental and neurological disease, and gene-environment As can been seen, for all of these institutes the predominant interactions. mechanism is the research project grant, primarily the R01 6. Advanced Instrumentation and Computers in Medicine or investigator-initiated grant-in-aid. Beyond this, individual and Research ($20 million), with emphasis on early detection

6 1360 KRESINA HEPATOLOGY November 1997 of cancer; determination of DNA sequences; improvement of REFERENCES links between research groups and physicians; and visualiza- 1. NIH Data Book (Basic Data Relating to the National Institutes of tion of the nervous system and the eye. Health), Office of Science Policy and Technology Transfer, Depart- ment of Health and Human Services, Public Health Service, Acknowledgment: The author gratefully acknowledges 2. Extramural Trends and Data Book. (Basic Data Relating to the National Institutes of Health), Office of Science Policy and Technology the critical review of the manuscript by Dr. Jay Hoofnagle, Transfer, Department of Health and Human Services, Public Health Dr. D. Montgomery Bissell, and Dr. Jackie Maher. Service, APPENDIX For Liver and Liver-related research projects, individuals that can be contacted are: Name Affiliation Address and Phone Number Andre J. Premen, Ph.D. NIA Geriatrics Program, Gateway Bldg., Room 3E327 (301) Dr. Vishnudutt Purohit NIAA Health Scientist Administrator, Willco Bldg., Room 402 (301) Dr. Dennis R. Lang NIAID Microbiology and Infectious Diseases, Solar Bldg., Room 3A-21 Dr. Leslye D. Johnson (301) Dr. Andrew Chiarodo NCI Chief, Organ Systems Coordinating Branch, Executive Plaza Bldg., Room 512 (301) Dr. Ephraim Y. Levin NICHD Medical Officer, Endocrinology, Nutrition and Growth Branch, CRMC Bldg. 61E, Room 4B11 (301) Dr. Eleni Kousvelari NIDR Director, Salivary Research and Organ Biology Centers Program, Natcher Bldg., Room 4AN-18A (301) Dr. Thomas F. Kresina NIDDK Director, Liver, Biliary and AIDS Programs, Bldg. 45, Room 6AN-12A (301) Dr. Geraline C. Lin NIDA Project Officer, Biomedical Research Branch, Division of Preclinical Research, Parklawn Bldg., Room 10A-19 (301) Dr. George Malindzak, Jr. NIEHS Program Administrator, Organ Systems Toxicology Branch, Mail Drop 3-02, P.O. Box 12233, Research Triangle Park, NC (919) Dr. Scott Somers NIGMS Program Director, Pharmacology, Physiology and Biological, Chemistry, Natcher Bldg., Room 2AS-49J (301) Ms. Nancy Ernst NHLBI Nutrition Coordinator, Two Rockledge Center, Room 8112 (301) Dr. Fred Altman NIMH Chief, Behavioral Medicine Program, Health and Behavior Research Branch, Parklawn Bldg., Room (301) Dr. Robert Zalutsky NINDS Program Analyst, Legislation and Analysis Branch Bldg. 31, Room 8A03 (301) Dr. Hilary Sigmon NINR Program Scientist Administrator, Natcher Bldg., Room 3AN-18 (301) Dr. Bernard Talbot NCRR Medical Officer, GCRC Program, One Rockledge Center, Room 6124 (301) Dr. John Chah Office of Alternative Research Development and Investigation, Mail stop 2182, Bldg. 31, Room 5B-38 Medicine, OD (301) Dr. Mushtaq Khan DRG Scientific Review Administrator, GMA-2 Study Section, Two Rockledge Center Room 4124 (301)