SPECIFICS ABOUT THE ETHICS PROGRAM

Question. You have stated that you intend to devote 38 of your budget to studies on ethical and legal issues related to the genome project. Can you be more specific about what types of activities you plan to support in this area? What are some of the questions that you think are most important to address? Will this simply be an academic discussion or will the public be involved?

Answer. The successful accumulation of genomic information will require that we as a society be prepared to know how to use that information sensibly for the benefit of individuals and society as a whole. The goal of our ethics program is to define the problems that may arise and develop useful safeguards, as well as provide information to the public. We have organized a joint NIH/DOE working group on ethics, legal, and social issues to provide us with advice on how best to achieve this goal. This group is now working on defining the research agenda and has recently held a workshop that brought together a number of interested scientists and non-scientists to discuss priorities in this area and to help plan a series of town meetings that we intend to sponsor in 1991 to solicit public input on these issues.

We also plan to support conferences that will bring geneticists together with lawyers, bioethicists, sociologists, theologians, representatives from labor, and the insurance industry to discuss the impact of the information generated by the Human Genome Project on their particular areas.

Additionally, we will support research training of scholars and scientists who wish to study ethical, legal, and social implications of the genome project.

INVOLVEMENT OF MINORITY INVESTIGATORS

Question. Tell me how you propose to increase the involvement of minority investigators in the human genome project?

Answer. The NCHGR is anxious to have minority students and faculty participate in our research and training programs.

We recently sent letters to all NCHGR grantees advising them of the Minority Supplement Program established by the NIH and encouraging them to apply for supplements to support minority students and faculty interested in genomic research. We are preparing to send a similar letter to the program directors of the Minority Biomedical Research Support grants and the Minority Access to Research Career grants. Additionally, we plan to fund eight students under the Minority High School Student Research Apprentice Program sponsored by the Division of Research Resources. Through this program we hope to kindle an interest in genomic research in those very young people needed to see this Project through to completion.

Furthermore, we are currently having discussions with leaders of the Association for Minority Health Professional Schools (AMHPS) and the director of the Research Centers in Minority Institutions (RCMI) program about sponsoring a scientific conference involving scientists from minority schools to discuss the Human Genome Project and how these schools can participate.

WHY THE ENTIRE GENOME APPROACH?

Question. Many scientists believe that the genome project should be approached by first targeting the study of disease genes or other interesting genes. Why have you not chosen this approach for the project and what is the advantage of the approach you have chosen? How are the results of the genome project being communicated to scientists who are more directly studying human disease? Are these scientists participating in the project?

Answer. We have chosen to approach the project from the point of view of the entire genome because we believe that this is the only way in which we will accomplish the whole project. The gene by gene approach would lead to a loss of momentum because we would become prematurely engaged in the analysis of the biology of an interesting region and because we would be likely to

completely miss regions that will turn out to be extremely important but which do not appear to be interesting at this time. While I encourage genome scientists to begin to analyze interesting regions as they map and sequence them, I believe that we would miss important information in the unexpressed DNA if we concentrated only on the expressed regions.

The results of the genome project are being communicated to other scientists in many ways, including the normal channels for the distribution of scientific results: publications, scientific meetings, and databases. We are also looking to improve existing databases and develop any new ones that will be necessary to make the products of the genome project readily available to those scientists who need and want them.

Many human geneticists are involved in the project through individual research grants and we expect more to be involved through the research centers and research training programs. While we do not intend to fund searches for individual genes, we do encourage projects that involve improvement in the technology available for identifying genes of importance. Human geneticists are actively involved on all of the advisory committees, councils, and review panels that NIH uses in planning and effecting the genome project. We have developed close liaison with the American Society for Human Genetics, especially their committee on the human genome.

THE NUMBER OF HIGH QUALITY CENTER APPLICATIONS

Question. Dr. Watson, I see you plan to fund nine research center grants in FY 1991 compared to three in FY 1990. That is a large increase. Will you be able to get enough applications of high

quality?

Answer. I am confident that we will. We anticipate about a dozen applications for FY 1990, all from highly qualified groups. Since we have only budgeted for three centers this year, there will be carry over applications from FY 1990 that can be funded in FY 1991. In addition, we are already aware of several new applications that will be submitted for funding in FY 1991.

COMMERCIAL DEVELOPMENT OF INVENTIONS

Question. How will you make sure that the inventions coming out of this program are developed commercially as effectively as possible?

Answer. On February 22, 1990, I met with the Industrial Biotechnology Association (IBA) at their annual meeting. We are anxious to improve communications with all the interested industrial groups and develop a plan for how we can assist them. We are currently recruiting for an individual who will specialize in this area to join our staff. The role of this individual will be to make sure that industry has rapid access to our information and to make us aware of industry needs and any barriers that are impeding technology transfer so that we can deal with them.

COORDINATION WITH OTHER INSTITUTES AT NIH

Question. How are you coordinating your project with the other Institutes at NIH which are pursuing the isolation and analysis of specific disease genes?

We

Answer. At the NIH we have a coordinating committee for this purpose. provide information regularly to the other Institutes, my staff has visited a number of the Institutes and their Advisory Councils and conversely they have sent representatives to our Advisory Committee meetings. In organizing conferences we generally include individuals who are likely to use the data and technology produced by the genome project and are grantees of other

Institutes.

QUESTIONS SUBMITTED BY SENATOR ARLEN SPECTER

Question. Dr. Watson, I understand it is estimated that the Human Genome Project, when fully operational, will cost $200,000,000 per year. The fiscal 1991 budget requests an increase of over 80% for this project, but the NIH as a whole receives less than a 4% increase. In lay terms, how do I respond to the people of Pennsylvania when they ask me why we are spending so much on this single project?

Answer. I believe that the Human Genome Project represents an extraordinary opportunity to make a significant advance in our understanding of human biology. Genetics has been a significant component of the research programs of many, if not all, of the Institutes at NIH for years, increasingly so over the past decade. One aspect of this work has been the mapping and sequencing of individual genes. Thus, the NIH has been supporting genomic analysis, but in a necessarily piecemeal manner. In contrast, the genome project will accomplish the characterization of the entire genome of the human and other organisms in a systematic manner. I believe that this approach will make this significant information resource available to the scientific Community much more rapidly, much more completely, and in a much more costeffective manner than would otherwise occur. In turn, this will aid the biomedical and biotechnological research communities in their attempts to improve the health status of the U.S. public and the economic status of the U.S. biotechnology, pharmaceutical, and other industries.

With regard to the increase in the budget for the NIH component of the Human Genome Project, this is a new program that needs to grow to a mature size rapidly in order to be completed within the time frame proposed. The rate of progress in scientific achievement that we have witnessed in the past 2 years is evidence that the program can usefully sustain this rate of growth. For example, scientists have recently shown that they can construct overlapping sets of human DNA clones representing about 2 million base pairs of DNA. This is in contrast to the situation just 2 or 3 years ago, at which time the region that could be isolated in this way was only about 200,000 base pairs in size.

Question. When this project is completed, how will the data be used and how will it contribute to understanding and treating disease?

Answer. The ways to use information developed by the Human Genome Project will be myriad, limited only by the imagination of the scientific community. When finally interpreted, the genetic messages encoded within our DNA molecules will provide the ultimate answers to the chemical underpinnings of human existence. They will not only help us understand how we function as healthy human beings, but will also explain, at the chemical level, the role of genetic factors in a multitude of diseases such as cancer, Alzheimer's disease, and schizophrenia, that diminish the quality of the individual lives of so many millions of our people.

By knowing the structure of genes, we will be able to design and test, in an informed and targeted manner, a variety of new therapies. One particularly exciting possibility is targeted drug design, in which new medicines are planned at the chemical level based on their predicted interaction with the specific proteins that are affected in particular diseases. While the ability to do this will depend on research advances in the area of structural biology as well, genome data will be essential for rapid progress in this area.

NATIONAL LIBRARY OF MEDICINE

STATEMENT OF DR. DONALD LINDBERG, DIRECTOR

SUMMARY STATEMENT

Senator HARKIN. Last, Dr. Lindberg, National Library of Medicine, we appreciate the efforts you pursued over the last year to increase the outreach of your services to world communities and the underserved areas of the country. We have talked about that before, and I am pleased to see your progress in those regards.

For fiscal year 1991 you are asking for $89.92 million, a 4.89-percent increase. Welcome.

Dr. LINDBERG. The mission of the National Library of Medicine is to acquire, organize and disseminate the biomedical information of the world for the benefit of the public health.

That has been quite well understood for 154 years, but things are changing fast. We are rapidly finding that we are truly in an information revolution and a computer age. To a great extent, NLM is at the center of those aspects that concern biomedicine.

I think some of the examples of the priority programs I mention to you will illustrate that for you.

During the last year we performed 5 million online searches; that is up 4.5 from the year before. There are 50 subset licenses to commercial and university clients. There are 17 overseas centers for MEDLARS services.

We are now using CD-ROM's, a new electronic form of the MEDLINE data base. In this case, they were developed with 10 private information vendors. We did it that way because marketing research was needed rather than basic research.

Senator HARKIN. What do you have on those?

Dr. LINDBERG. The CD-ROM's are magnetic recordings of the MEDLINE data base. They are on 54-inch disks which can be used on the little machine, very similar to the audio machines. With them the data base would be available on one's desk.

They are still somewhat expensive in that they are sold to institutions like libraries, medical schools, or partnerships. They are sold by commercial outfits to whom we lease the tapes-we guarantee the quality of them-and they are now present in 45 countries. The information is really reaching the Third World and beyond, as well as the United States. The CD-ROM provides on-your-desk service to places in the world where we cannot get our services directly. This is in addition to the 5 million inquiries of the NLM online system.

NATIONAL CENTER FOR BIOTECHNOLOGY INFORMATION

Another example of the new information age being upon us is the faith the Congress had in creating the National Center for Bio

technology Information 2 years ago. I should report to you that it's off and running and a great success. The brilliant new director of that group, Dr. David Lipman, is working extremely well with Dr. Watson and his colleagues and others around the country.

They have the mission to do research on the new information systems needed to handle this wealth of new sequence and mapping data, to be simple about it. There are lots of details to it, of

course.

By way of a kind of breakthrough, I thought I would mention the thing that Dr. Lipman told me last week. One of the basic things one would assume would be done when any data is deposited in the genbank or the depository for sequence data, is to ask the question: Is what I have just put in identical with or like something that is already there? In other words, is it a discovery? Is it a real addition?

Now you would think, just as a bank would ring up your deposit and verify it against the account, that this would be automatically done, but it's not. It is not done automatically by any stretch of the imagination. It has to be requested. It is an overnight service. It takes hours on a big computer.

Last week Dr. Lipman and company found a new way to do it with a program they call BLAST, in which any sequence you specify can be compared with all the sequences-30 million I guess now if I am not mistaken, in 5 seconds. So while you hold your breath, the whole comparison is done.

We are very proud of that, but also knowing that with the progress Dr. Watson and his centers will make, there will be 1,000 times, maybe 1 million times as much data by the time his project finishes. So we have to keep working on the informatics as well.

AIDS INFORMATION SERVICES

In the AIDS area, the Congress required certain new information systems of us, and broadly these are successful. There are data bases such as AIDSline, AIDStrials, AIDSdrugs, and they are all running.

OUTREACH

Our top priority in the last year has been the outreach efforts as the chairman mentioned, and as recommended by the DeBakey panel as part of our long-range planning effort. The panel told us to be sure that American health care professionals are aware and capable of using the innovations and information systems that we are developing.

We should be prepared to provide health professionals with access but they have to meet us half way. We have to go out and be sure that they are informed and using the best systems that are available.

The panel urged us to work through the existing regional medical library network to initiate a new series of grants and to improve library access and information system grants, to continue the IAIMS programs, to train more health care professionals in computer systems, to create a kind of production line of new products