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Now, as far as significant advances, I think we were asked last year by Congress to look over our budget and to say are we really going to meet the $3 billion figure. So, we have presented to Congress a reevaluation of the program, and it really falls into two parts.

The first is looking at the mapping problem. Here there has been a series of technological developments which really ensure that the mapping can be done for approximately a $500 million sum. So, we are very confident that that can be done. And this will be very important. This is the part of the project which will directly lead disease gene hunters to that section of the chromosome where they can home in on their gene. It was knowing the map position which let Francis Collins find the cystic fibrosis gene. You have to know the map position. That is why we have concentrated on maps and now we can make them. Because we know how to make them, we have created a number of specific human genome research centers whose function is to make these maps and get them out to the medical researcher. We think this will really permit a much larger number of people to join in the effort to find disease genes.

The second effort we are moving on is the whole question of actually working out the exact messages, what we call DNA sequencing. Currently, sequencing costs roughly 10 times more than we believe it should, and so a great deal of our emphasis is placed on trying to develop new technologies which will reduce the costs. Over the next 5 years we think we can achieve this reduction but, of course, until we do, I cannot say we have accomplished our goal. We have put out a number of grants with the aim of sequencing roughly 1 million base pairs per year. Now, there are 3 billion of them, and we want to get people up to the point where 1 billion base pairs does not seem like a big effort. A lot of that will be done by machines, and the machines that conventional wisdom said aren't that good really are good. We have been encouraged over the past year that a machine-I am happy to say it is an American machine-probably can do much of the job.

Now, the last thing I want to mention is that we are very pleased to have set up our ELSI program—that's the ethical, legal, and social implications program. Due to the throws of the genetic dice, some people have a better opportunity for living a fuller life than others, and we are very concerned that this new genetic knowledge does not lead to a form of a genetic underclass which will not only get a bad throw of the genetic dice, but then be treated worse than other people by society as a whole.

Senator HARKIN. I'm sorry. I want to understand what you just said, Dr. Watson.

Dr. Watson. When you are born-
Senator HARKIN. Yes.

Dr. WATSON (continuing). The exact genes you get are one-half your mother's genes and one-half your father's genes. Now, as a result, children in a given family don't always look the same, they are very different at times. Sometimes they can look quite similar, sometimes very different. When you make a gene, the copying process isn't always perfect. It is largely perfect, and that is, of course, why we can exist. But occasionally it goes wrong and you get a gene such as is responsible for muscular dystrophy. The gene isn't copied correctly. So, some people are going to inherit faulty genes, and faulty genes will always be here because they arise from mistakes in DNA replication.

Now, muscular dystrophy tends to occur in boys, and it depends which of the two chromosomes from your mother you inherit. You can get a good one or you can get a bad one. So, that is why I say there are some people who are victims of unjust throws of the genetic dice. It is not their parents' fault. It's not their fault, but they've got it. What we have to do is develop ways to treat these people compassionately, both in trying to cure their diseases and in trying to take care of the disabilities which they may have to live with throughout their lives.

So, that is really why we have to have a strong ethics program. When I took over, I said we should spend 3 percent of our money on ethics. In fiscal year 1991, we hope to spend 4 percent and in fiscal year 1992, 5 percent. This will be a growing program. And, of course, the disabilities law which you have helped bring into existence is one which can protect, in part, people who are victims of their genetic heritage. So, we view this ethics program as important as any other aspect of our program. It cannot precede the program. It has to go hand in hand with it because often the exact ethical issues you will face you will only know when you see your bad gene. You will know really what dilemmas it creates. So, they have to go hand in hand. We have an excellent advisory committee on these issues. We have a very strong person, Dr. Eric Juengst, running it in our office, and it is perhaps going to be our most visible component because that is what the general public wants to know, how this is going to influence their lives.

PREPARED STATEMENT

So with that, I will say that the fiscal year 1992 request for the National Center for the Human Genome Research is $110 million

this year.

Mr. Chairman, I will be pleased to answer your questions. (The statement follows:)

STATEMENT OF DR. JAMES D. WATSON

Mr. Chairman, I am delighted to have this second opportunity to share with

you and the members of the Committee my enthusiasm for what I believe is one

of the most exciting and significant biomedical research undertakings of this

century.

With strong support from the Congress and the Department of Health

and Human Services, the Human Genome Project officially began work on its

goals for the first five years on October 1, 1990.

I am pleased to describe

to you today the accomplishments we have already achieved as well as the new

initiatives the National Center for Human Genome Research (NCHGR) has laid out

to reach its goals as rapidly as possible.

Indeed, the faster we accomplish

these goals, the sooner we will get on with the business of truly

understanding the complex contributions our genes make to so many, trágic

human diseases.

Very simply, the goals of the Human Genome Project are to develop

biological maps for each human chromosome and to read the genetic text written

in the chemical sequence, or letters, of human DNA.

DNA is the substance that

carries genetic information contained in the chromosomes of all plants and

animals.

Why should we do this?

Because we believe it is the only way we will make

swift progress toward understanding the thousands of human diseases caused by

malfunctioning genes.-diseases like Huntington's, Alzheimer's, birth defects

of all sorts, Tay-Sach's, and scores of other metabolic defects.

Faulty genes

also most certainly contribute to the more common killers of our day--cancer,

diabetes, high blood pressure, and heart disease.

Over the

past several

years, biomedical research has increasingly looked

to the gene to understand the mechanisms of human disease.

The tools of

recombinant DNA technology, which were developed nearly 20 years ago, have led

us to the doorstep of that knowledge. They have given us provocative glimpses

of the wonders we might work if we could only cross the technological

thresholds that now keep us from understanding the molecular essence of

genetic disorders.

We have undertaken the Human Genome Project to provide biomedical

researchers with the technologies and information they need to step across

that threshold and into new arenas of understanding and progress.

Chromosome

maps will lead researchers more quickly and much more cheaply to the genes

they wish to find. They will enable younger researchers in smaller

laboratories..those who now do not have the technological resources for

genomic research--to apply their ample talents to research problems that now

evade them.

A second product of the Human Genome Project, the chemical sequence of

human DNA, will give researchers the information they need to understand what

genes actually look like.

We must be able to "see" genes in their most

exquisite detail before we can begin to learn how they function in health and

malfunction in disease.

The chemical sequence of human DNA will also offer

the basis for strategies for development of new classes of drugs for treating

diseases.

with the establishment of Human Genome Research Centers at U.S.

universities, NCHGR began its support of large-scale, high-resolution mapping

of entire human chromosomes.

These centers will focus on physical mapping of

large, connecting expanses of human chromosomes as well as development of new

technologies to store and analyze genome research data generated in these

projects.

NCHGR now supports large-scale mapping of chromosomes 4, 7, 11, and

X.

In the coming year, we plan to award new centers to expand our support of

whole-chromosome mapping research.

In addition, NCHGR-supported researchers began a large-scale effort to

develop a physical map of the mouse genome. Because of the close similarities between the mouse and human genomes, this project will provide valuable

information to the large number of health researchers who use the mouse in

comparative studies to gain insights into the structure and function of human

genes.

Two important NCHGR initiatives begun in FY 1991 are aimed at delivering

powerful new tools to the biomedical research community in a very short time.

The first, an initiative to construct a "framework" map consisting of 300 or

so evenly spaced, high-quality markers among the human chromosomes, is slated

for completion in the next two to three years.

As these markers begin to

enter the public domain in FY 1992, this so-called "index" map will likely be

the first research tool the Human Genome Project dispenses to the research

community.

Index markers are expected to be especially useful to scientists

in search of genes responsible for diseases and other biological traits.

The

index map will serve as an extremely useful interim tool until the complete

map of all the human chromosomes is finished, which we anticipate well before

the turn of the century.

With the second initiative, we have begun to tackle the technological

problems of DNA sequencing. Sequencing DNA, or determining the order of its

letters, is now the backbone of the body of biomedical research that seeks to

understand how genes control cell function.

Because DNA sequencing is very

time consuming and expensive with current methods, the secrets of genes are

locked away in indecipherable DNA sentences.

These sentences consist of long

strings of only four letters, ordered in very precise ways.

If we could read

these sentences easily, we would have access to the genetic instructions that

control the chemical processes in our cells.

We know already that errors in

these sentences result in genetic defects and supply cells with misinformation

about how to function normally.

Several projects to improve the efficiency, accuracy, and cost of DNA

sequencing were begun by NCHGR-supported scientists this year.

These pilot

sequencing projects will focus on biologically important sites in the human

genome and on the genomes of model organisms, including the common intestinal

bacterium E. coli, yeast, a roundworm, and another bacterium known as

Mycoplasma, which are of broad interest to the large sector of researchers

studying the basic biological structure and function of genetic molecules.

Recent ex

ience has shown that many of the genes of these model organisms

are extraordinarily similar to human genes, so the knowledge gained will

simultaneously benefit medical research.

The main objective of these pilot DNA sequencing projects is to bring down,

cost.

We will not support systematic sequencing of the human genome until

costs are low enough and technology good enough to do it efficiently.

This year we will begin supporting studies of molecules called

complementary DNA, or cDNA.

These molecules will lead scientists to DNA

regions that are actually known to instruct a cell to produce proteins.

While

some genome scientists are working to isolate large segments of human

chromosomes, others will be using cDNA and other methods to develop new

technique's to scan those regions for active genes.

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