Genes a A New Measure of Man
William A. Haseltine
Human Genome Sciences, Inc.
About the Lecture
In perpetual search of self, we ask: What are we? Whence to we come? Whither do we go? What distinguishes us from other living things? What distinguishes the quick from the dead? What is our place in the natural world? We are on the brink of a new set of answers to these vital, age-old questions. Our entire genetic blueprint will soon be open to view to provide yet another set of answers to these questions.
What are we? Our form and function are determined by a set of genes each specifying a small element of our design. We are our genes, and now we know them. Whence to we come? What we call ourself is the physical manifestation of the DNA molecule that encodes our genes. This DNA molecule has passed for three billion years, from generation to generation.
The DNA molecule within us is, in a very real sense, the same molecule as existed long ago. Our past is our present. Whither do we go? Our knowledge of genes has the potential to free us at last, from the whims of chance that have guided our physical destiny. Whither we go, is now a matter not only of chance but also of will. What distinguishes us from all other living things? All life is related by a thread called DNA. In a deep sense, all life is one.
What distinguishes the animate from the inanimate? We are molecular machines, each piece architected at atomic resolution, each piece shaped by the information of our genes. There is no fundamental difference between the animate and inanimate. All are subject to the same cosmic laws. What is our place in the universe? How far down we have stepped from our classical pillar—at the center of the universe, we now see ourselves as inhabitants of a speck circling a spark. A genetic and molecular understanding reduces unique characteristics still further. We are of earth, from earth, to earth.
About the Speaker
William A. Haseltine holds a doctorate from Harvard University in Biophysics, and is a Professor at Dana-Farber Cancer Institute. Currently on leave of absence from Harvard Medical School and Harvard School of Public Health, he is the CEO of Human Genome Sciences, Inc., a Rockville, Maryland company working in the area of research and development related to novel genes from human, animal, plant and microbial origin.
The President, Mr. Ohlmacher, called the 2038th meeting to order at 8:27 p.m. on January 20, 1995. The Recording Secretary read the minutes of the 2036th meeting and they were approved with a correction. The President then read a portion of the minutes of the 430th meeting January 19, 1895.
The President introduced Mr. William A. Haseltine, President, Human Genome Sciences to discuss “Genes — A New Measure of Man”.
It had long been observed that “like begets like”, but close observation of how inheritance of measurable traits really appeared to work (by Gregor Mendel and his successors after 1900) led to an initial, abstract definition of the gene. A gene is a discrete, nonmiscible, heritable trait. The nonmiscible aspect is most evident in the reappearance of recessive traits in the offspring of hybrid parents. DNA is now recognized as the physical material that embodies the abstract concept of genes. The most fundamental characteristic of DNA as the material of genes is that it manages to duplicate itself exactly on an atomic scale. Our current understanding leads us to a physical and functional definition of the gene. A gene is a length of DNA that specifies the biochemical instructions to make something, like a protein. When occasionally a new trait does appear, there has been a variation in the structure of a gene, a mutation, resulting in a change in a single piece of information, and altered instructions have led to the production of a different product.
The new medicine enabled by these advances uses our own genes or gene products to correct or overcome disease. We now have the means through genetics to produce human proteins in other organisms, and harvest those proteins to use as drugs. Genetics can be used to predict future health patterns and problems. To continue these advances and use them effectively it is important that we have and be able to understand the total collection of human genes. The Human Genome Project began at the DOE and is being carried on by the DOE and the NIH.
The technology of Expressed Sequence Tags (EST) was developed as one part of the Human Genome Project. EST technology isolates pieces of DNA from genes whose instructions are being actively interpreted. For various reasons this became an orphan technology that could not be conducted at or funded by the NIH. Human Genome Sciences took up this orphan technology, and after two years we believe we have now been able to isolate EST's from at least 95% of all human genes. This has been accomplished by means of robotics. The processes of picking colonies of cells from growth medium plates, growing those cells, isolating the EST's from their DNA and sequencing them have all been automated. We have a factory that produces information about the human body on an assembly line basis. Prior to our work 4,000 EST's had been isolated and sequenced. We have isolated 800,000 EST's and sequenced 400,000 of them. We can estimate that we have EST's from 95% of the human genes, because 95% of all known gene sequences can be found in an average of 4 of our EST samples, and each new gene reported can be found among our EST samples 95% of the time.
In answering some age-old questions we would now say that we are atoms. There is no material difference between animate and inanimate, except in the level of organization of the material and its energy. Having a complete collection of genes can give us a deeper appreciation of how closely related we are to other living organisms. We know that life began about 3 billion years ago and was relatively stable as single-cell and simple multicell forms until about 600 million years ago when sex appeared and evolution really took off.
Approximate number of genes
bacteria (Escherichia coli) 3,000
yeast (Saccharomyces cerevisiae) 6,000
worm (Caenorhabditis elegans) 12,000
fly (Drosophila melanogaster) 30,000
mammal (Homo sapiens) 100,000
The 3,000 genes in bacteria probably represent the approximate minimum number of genes that would be required by a self-reproducing organism. The increasing numbers of genes beyond that appear to arise chiefly by replication and variation of the basic set.
In addition to enabling us to correct and overcome disease and to predict future health patterns and problems, these new genetics technologies will also permit gene therapy. Even more controversial, it will permit manipulation of the genetic heritage. The genetic future need no longer be a matter of chance.
The President thanked the speaker on behalf of the Society. The President presented the name of one new member. The President then announced the speaker for the next meeting, made the parking announcement, and adjourned the 2038th meeting at 9:56 p.m.
John S. Garavelli