It is called a "human library", but it is not a roomful of books about humans nor is it a collection of people.
It is a little tube half a finger high, which sits in a rack in the refrigerator in Thomas Maniatis' lab at Harvard University. The tube holds the DNA, short for deoxyribonucleic acid, specifying one whole human being. In this case it is a female lab assistant who donated a few cells to make the library.
There are other libraries in Maniatis' refrigerator, and others around the country: monkey libraries, sea urchin libraries, rat libraries, frog libraries. They are key elements in gene engineering because scientists now can order a human library, and from it extract any gene for study.
Each library contains all the genes of one human, cut into 150,000 pieces, each piece long enough to contain only a few genes. To pick out single genes for study and manipulation is a totally new capability in science, and these little libraries are the source of genes for many experiments.
Genes are the particles of life, the strings of information that govern all the life chemistry of creatures on earth from bacteria to dandelions to frogs to man.
Until recent years man did not know what genes are made of, or how they worked in even roughest terms. Now scientists know genes atom by atom. They can manipulate them and the critical chemicals they make to govern life.
The power to manipulate genes has allowed scientists to make stunning advances in fields ranging from the study of the immune system to cancer research, to public health, to agriculture, to the study of evolution and human history.
From the human library, a scientist can pick out by chemical processes any gene to study. It may be the gene that makes insulin, or inteferon, or hemoglobin, or any of the other critical substances in the human body. Then--and the entire existence of scores of new biotechnology companies depend on this--bacteria can be made to accept the foreign gene so they will manufacture its products as if they were their own.
The little bits of DNA called plasmids in the bacteria can be cut open chemically. The new foreign gene can be inserted and the plasmid chemically closed again. Thus baker's yeast, intestinal bacteria and other such common bugs can be made to produce easily, cheaply and in infinite amounts any substance made by genes in plants, animals or man.
Among the substances already made in addition to insulin and inteferon are the human growth hormone, different constituents of pharmaceuticals, proteins that will make vaccines for foot-and-mouth disease and dozens of others.
Dwarfs lack the substance that triggers growth and it is so difficult to obtain that it takes many human corpses to draw off enough hormone for a single patient. Now, the material is made easily by gene-engineered bugs and is being tested for safety.
Vaccines against hepatitis, malaria, venereal disease and a variety of agricultural diseases such as foot-and-mouth, are now being developed by gene splicing techniques.
Enzymes, natural chemical catalysts that make possible a great variety of critical chemical changes, such as turning sugars into alcohol and separating valuable metals from rock, may be made in quantity at a fraction of the current cost.
In agriculture, one of the genes recently isolated and cloned is one that helps prevent plants from drying out in drought. The most talked-about, but far off, advance is one that would make plants self-fertilizing. It would give them the ability to make their own nitrogen sources, as some bean plants do, rather than having to depend on the easily-depleted nitrogen in the soil.
The useful products that will be made with gene engineering techniques, by the most conservative estimates, will have sales measured in the billions of dollars every year. Some estimates go as high as several hundreds of billions per year. Other profound advances include:
GENES AND RACE. One of the most interesting results of the new biotechnology historically and philosophically is a sort of biological archeology that excavates genes to discover the minute genetic differences and similarities between species or to find out when one group split off from another in evolution. One interesting finding, for example, is that the hemoglobin genes of baboons, gorillas and humans are virtually identical.
One of the first general findings involves the question of race. For centuries it has been assumed that humans are naturally divided into large groups called races, identified by a few traits such as skin color and some facial features.
But now it appears that if humans are grouped by how similar their genes are racial groups dissolve. The new picture of human groups makes it clear that humanity around the globe is a uniform group. Genetic differences occur randomly for the most part among indviduals.
"The idea of racial type and, some would argue, of race itself is no longer a very useful one in human biology," says British biologist J. S. Jones in a recent article in the journal Nature.
Genetically speaking, Europeans and Africans are closely related. Both are signficantly different from native Americans, Australian aborigines and Asians. In one test of the genes of 21 people from around the world, the two most nearly identical were a European and an African.
A study of 180 different human populations including six major racial groups found that 84 percent of the genetic differences between people are individual, not racial. Another 6 percent of difference between humans comes from being part of different tribes or nationalities--the difference between the French and Spanish, or between two regions of a nation--and again has nothing to do with race.
CANCER GENES. Within the past three years biologists have also suddenly been able to find, pick out and study the genes that transform cells from normal to cancerous, clues that will probably quickly lead to an understanding of the causes of cancers, though not necessarily cures.
Three years ago, by using the new genetic engineering techniques, researchers found that large pieces of DNA removed from cancer cells and implanted in normal cells can transform the normal cells into cancerous ones. Recently three separate laboratories have located and isolated cancer genes from a variety of different cancers, including cancers of the colon, bladder and lungs, as well as leukemia.
Radiation, chemicals, sunshine and other things are known to cause cancer. It now appears that they trigger cancer by damaging one or a few genes that control growth and keep it at a normal pace. These growth-controlling genes apparently are needed for rapid growth in the early stages of an animal's development and are turned off as the animal matures. But apparently these genes can be restarted by accident to disastrous effect.
THE GENES OF IMMUNITY. One of the best examples of the power of the new technology is how it has solved key mysteries about the body's immune system.
Philip Leder, head of the National Institutes of Health group investigating the immune system, sat up in his attic laboratory some days ago, enthusiastically describing the recent advances.
He proudly showed off his unusual portrait of his family--rows of black smudges on photographic paper. They were pictures of a few genes in each family member. " . . . And this is my daughter. You can see this gene she got from me, and this one from her mother," Leder, the doting father, said.
They are the first such family pictures, and until a few years ago could not have been made. Now, such pictures should quickly end all questions of parenthood in the courts. A few discrete gene photos, comparing genes of parents and children, should end any dispute.
Leder's area of study is the immunesystems. The problem facing the body's immune system is a classic one, not only in human life but in the evolution of man.
The body has been built into a sturdy organism not by making rugged, rigid parts to defeat the ravages of the world. Rather, it is a system that is vulnerable, but has parts able to react quickly and effectively to most dangers.
The immune system is in charge of the body's defense against the hundreds of millions of viruses, bacteria, poisons and damaging chemicals that need to be recognized and disabled. The body cannot tell ahead of time which of the hundreds of millions will suddenly enter the system. In fact, some of the dangerous substances it will face never existed on earth before they were recently created by man.
Still, the immune system can recognize and disable each of these new chemicals and hundreds of millions of other possibly lethal substances. It does so with antibodies. Each antibody is specific; it recognizes one chemical substance among the hundreds of millions of hazards and immobilizes it.
Leder and his colleagues began work in the late 1960s, but progress was slow until the new gene technologies appeared. With the technology, Leder said, "We have learned things quickly that we couldn't have hoped to learn for decades, possibly not at all, without these approaches."
"Your body has to be ready to synthesize antibodies against chemicals, all kinds of them, some that have not appeared on the face of the earth yet. And very quickly," Leder said. "Your survival depends on it.
"It all depends on the ability of the system to generate an enormous number of different molecules. You've got to be able to make a hundred million or more, not all at once but quickly, when one is needed. Now that is a hell of a load, a hell of a genetic load. You probably don't have more than a million or so different genes, total," he said.
Each gene in the body can direct the making of only one substance, and all but a few of the million genes in the body are tied up making other substances. So how is it possible for the immune system to produce hundreds of millions of specific immobilizing antibodies?
The answer begins with a fact discovered about genes only in the past couple of years, a fact that transformed thinking about the gene system.
Before then it was believed genes were solid and stable, only occasionally being damaged in one "letter" of its genetic code, changing only gradually over time. The gene was read and copied, and the copy after moving out into the cell made the gene product it was directed to.
But this picture has been proved wrong.
Leder displayed an electron photomicrograph of a piece of DNA showing a strand of DNA running along neatly, interrupted by a section in which the two strands split and had bubbled out from one another. "We caught a picture of this in mid-change. Another 20 million years," he added with a smile, "and it would have been too late."
In comparing DNA letter-for-letter for the first time, scientists were stunned to discover a whole piece of DNA blown out of place, or a segment flipped over so it reads backward, or a strange, useless piece of DNA stuck in the middle of a sequence.
Luckily, the damage in this particular piece of DNA did not affect the survival of the animal. If the burst strands had appeared in the midst of a gene, which makes up the DNA molecule, it would have been fatal. But this dangerous process, in which floating pieces of DNA can pop into the midst of genes, can lead either to nonsense and death or to entirely new and interesting genes. This is the mechanism of evolution.
A sudden, large change in an important gene may prevent an egg from growing even to fetal stage. Other changes may allow a person to live, but only a defective, brief life. One such genetic disease is called thalassemia, and it is a defect in the gene for making hemoglobin, the critical part of blood cells. The life of the thallasemic is one l way in the laboratory. We believe it can be proved on a large scale in less than two years."
Establishing the process for one product should establish it for hundreds of others because the gene technology to get an antibody to bind to some substance and to produce large amounts of it by putting it in the plasmids of E. coli or yeast will be identical in all cases.
The work with the immune system has scientists excited both for the logic of the system and the heady sensation of imbibing knowledge no man has had before. Businessmen are beside themselves with thoughts of the power and efficiency of this natural system doing things man has until now done only clumsily.
The immune system is only one part of the biotechnology boom. There is similar excitement over the knowledge, and the possible profits, in other branches of biotechnology.
For molecular biologists, who for so many years had been poorly paid laborers in an unknown field, the Trappist monks of science, the state of affairs may be described as nirvana.