Clues Gained on Path to Genetic Map : Science: About 600 scientists will gather here for the Third Annual Human Genome conference.
Scientists’ 15-year, $3-billion quest to identify the 3 billion chemicals in the human genetic blueprint is called the “Holy Grail” of genetics.
It also has been likened to a Rosetta stone that could revolutionize medicine, allowing doctors to treat diseases before there are even symptoms.
It also has been blasted as a pork-barrel project that will deprive individual scientists of funds and squash creativity as the big science endeavor sops up more than its share of money and talent.
The international Human Genome Initiative, described by some as the most important project in the history of biology, holds the promise of creating a genetic map that researchers could use to find and repair defective genes that cause diseases such as Huntington’s and Alzheimer’s.
“It’s like a manhunt for a criminal. If you don’t know where the criminal is, you can’t mount a good search,” said Theodore Friedmann, professor of pediatrics at UC San Diego and a pioneer in gene therapy. “But, if you know he’s in Des Moines or San Diego, you can surround the town and start looking.”
Starting Monday, about 600 of the world’s scientists will gather in San Diego for three days to discuss their progress and debate thorny ethical issues during the Third Annual Human Genome conference.
Although the endeavor is touted as international, about 75% of the research is now conducted by U.S. scientists, said Charles Cantor, the principal scientist for the Department of Energy on the Human Genome Project. England, France, the Soviet Union and Japan also are participating in the work, and U.S. scientists hope those countries will step up their involvement as the research promises to be beneficial to all mankind.
“This could be a turning point in medicine. Medicine is currently treating a disease once it happens,” said Ron Davis, professor of biochemistry and genetics at Stanford University. “But, with this, you can determine someone will suffer problems, and you treat those problems before they happen. . . . Many doctors have said that $3 billion is very inexpensive when you think of the impact on health.”
The same project, however, has been criticized by others as a folly that’s squandering scientists’ time and valuable resources.
“This project was so clearly pork barrel,” said Martin Rechsteiner, co-chairman of the biochemistry department at the University of Utah School of Medicine. “This is not scientifically valuable. It’s not a smart way to spend money. We don’t need to know this information, and I still maintain that most of this will be gibberish that we won’t be able to understand.”
But the chorus of opposition is clearly quieting as scientists plow ahead with the Human Genome Project, a scientific mega-venture with a $140-million budget for U.S. researchers for the 1991 fiscal year, Cantor said.
The human genome is the genetic blueprint of human beings. Deciphering this blueprint, or map, scientists believe, will eventually allow them to determine cures for as many as 4,000 diseases caused by single genetic defects and others that are caused by many genes working together that cause diseases such as cancer, diabetes, and alcoholism.
As a result of this project, scientists hope to create the gene map of a “generic” human being. This map will hold 3 billion bits of information, but among that mass of information, only one-tenth of 1% will differ between any two individuals, said Dr. Glen Evans, head of the molecular genetics laboratory at the Salk Institute. Because of the inherent similarities among individuals’ gene maps, the information will be universally useful.
Genetic information is encoded in DNA, or deoxyribonucleic acid. DNA is composed of chromosomes that hold smaller units called genes, which determine a person’s individuality. Humans have about 100,000 genes in 23 pairs of chromosomes.
There are four chemicals called bases in DNA. The 3 billion bases in the human genome are strung together like colored beads on a necklace. If the DNA in one human cell could be unwound, it would form a thread more than 5 feet long and less than 50-trillionths of an inch across.
Today, scientists are trying to identify the location of each of those 3 billion bases, a process called sequencing. It now costs $1 to $4 to sequence each base, Cantor said.
But, with 3 billion bases to identify, the cost is prohibitive. “We would spend every dollar on the bases alone, and obviously we can’t do that,” Cantor said.
Scientists are on schedule in sequencing DNA and mapping genes, which is slated to take 15 years, Cantor said. But that schedule depends on advances still expected to be made in laboratory technology.
“Progress is being made in bits and pieces,” said Davis of Stanford University. “It’s going to be slow. The problem is we can’t tell people that life is going to be better next year. There is not going to be much impact on Americans by next year; this is long-term.”
This week, scientists will grapple with several key issues, including whether to patent the sequencing information.
One of the most controversial issues to rock the genome community is whether it’s appropriate to patent the genetic information that’s being deciphered, said Dan Koshland, professor of molecular biology at UC Berkeley and an organizer of the conference.
Last summer during a congressional briefing, molecular biologist Craig Venter said that the National Institutes of Health plan to file a patent on his sequencing of the human brain genes. His announcement caused a firestorm.
“The argument is that, if you don’t allow some patenting, companies will be unwilling to go in on this,” Koshland said. “Others, however, say this is basic information, and one shouldn’t patent it.”
During the conference, scientists also will focus on several other issues, including:
* Model organisms. Because portions of genomes share similarities, scientists are sequencing animals and plants to help them pinpoint the locations and functions of human genes.
“We find sequences of other organisms are very helpful,” Koshland said. “You can’t carve up human beings. . . . Fruit flies aren’t cuddly and loving like cats, so people aren’t upset if you study their genetics.”
Scientists will present their latest discoveries on model organisms, having forged ahead with gene sequences of the fruit fly Drosophilia melangaster and the worm C. Elegans.
* Specific genes. Several scientists will present their efforts in deciphering specific key genetic sequences, including those responsible for causing the Fragile X Syndrome (a form of retardation), familial breast cancer, and a type of dysfunctional sexual development in males known as Kallman syndrome.
The quest for the human genetic blueprint is peppered with hurdles, including one basic problem: how to keep track of the flood of information that’s being generated. One human genome sequence, if written out, would fill 200 1,000-page phone books, Cantor said. But because scientists will be sequencing genomes for animals as well as plants, the sheer volume of information will be mountainous.
“It’s an explosion of information,” said UCSD’s Friedmann, who studies the X chromosome. “You can’t write things down in little notebooks anymore, and you need to have access to data all over the world. It’s a very difficult problem.”
The problem is so complicated that scientists have even coined a phrase for it: Infomatics, or how a mass of information can be efficiently stored and accessed.
In this way, scientists are trying to catch up to their own project.
“It’s like the space program. When the announcement was first made that we were going to have a space program, it wasn’t completely clear how to do it,” said Evans of the Salk Institute. “We’re now making tools, hardware as well as software, to do this.”
Last year, Evans and his colleagues at Salk received a $10-million federal grant to create a freezer-library of 16,000 DNA fragments that make up human chromosome 11, which has about 5,000 genes.
“Making a map of a genome is like assembling a jigsaw puzzle,” Evans said.
Today, scientists still don’t have enough of the jigsaw puzzle completed to help those suffering diseases.
“We know, for instance, that Huntington’s disease is on chromosome 4. But knowing that doesn’t help the patient,” Evans said. “But, if we know it’s there and, if we can find which gene, we can understand the causes of the disease, have diagnostic tests and get an idea of what type of therapy to apply.”
Genetic Blueprint
In the Human Genome Initiative, biologists hope to learn the identity of each of the 3 billion chemicals that make up the human genetic blueprint, known as the genome, in order to identify the causes of genetic diseases.
Each cell of the human body (except red blood cells) contains 23 pairs of chromosomes, each a packet of compressed and entwined deoxyribonucleie acid (DNA).
The 46 chromosomes contain about 100,000 short segments of DNA, called genes, that define all the characteristics of each human.
The genetic information contained in each gene is encoded in the sequence of four repeating chemicals, called bases, in the same way that information in words is encoded in the sequence of letters. The four bases are called adenine (A), thymidine (T), cytosine (C) and guanine (G).
