In what is being called a landmark of 20th-century biology, the worldwide effort to read the human genetic code has produced its first "text." Scientists have written out most of the message carried by one of the smallest packages of human DNA.
While they haven't yet deciphered its meaning, the move represents a milestone on the route to writing out the entire genome - the effort to list the order of some 3 billion chemicals that make up deoxyribonucleic acid, or DNA.
Ultimately, the endeavor could revolutionize modern medicine by helping scientists understand the biological roots of many diseases and, for the first time, treat them at the genetic level. At the same time, however, it leads toward profound ethical questions concerning the possibility of manipulating core human traits, such as intelligence, to create designer humans.
So far, scientists in various labs have produced about one-third of the genome in bits and pieces. Yet this is the first nearly complete text of a major genetic unit - one of 46 similar units called chromosomes that, together, carry a cell's nuclear DNA.
The chromosome text published in Nature today is "the first chapter" of a book that "will change the way we see ourselves as profoundly as did the momentous books of the first two millennia - the great books of religion and [Darwin's] 'Origin of Species,' " says biochemist Peter Little at Imperial College in London.
"If knowledge of gene differences can be combined with an understanding of the richness of environmental influences, we will have the key to unlocking the cause of most of the common disorders that kill or otherwise cause suffering," he adds.
Dr. Little doesn't expect the whole book to be printed. It would take up a half-million pages. Nevertheless, he does expect it will "inexorably alter our perceptions of human health, attitudes to each other, and understanding of our uniqueness."
It is in this sense that many geneticists believe decoding the human genome will open up a "Book of Life" - a phrase coined by James Watson, co-discoverer of the molecular structure of DNA.
Difference of opinion
But not all biologists see it that way.
They value a deeper knowledge of human genetics for the profound biological insight it provides, and they welcome its medical promise. Yet they note that knowing the genome better will not unravel the complexities of organic life, let alone penetrate the mysteries of human individuality.
Harvard University evolutionary biologist Mathew Thompson says it is "a clear mistake to call any [DNA] sequencing a 'Book of Life' " or even a "blueprint."
"Once you have the gene sequence, you don't really have a blueprint," Dr. Thompson says.
The same gene can have quite different functions in different organisms, he explains, using an automotive metaphor. If cars evolved biologically, what we call a carburetor could operate differently in different models. In one, it would function as a carburetor. In another, it might be an air conditioner. Yet we would call them both carburetors because they looked the same.
For this reason, Thompson says those researchers who speak in terms of "blueprints" and a "Book of Life" oversimplify a situation where "the scientific message is kind of cloudy."
The race to decode the human genome is under way in commercial, governmental, and university laboratories in Japan, Britain, Sweden, and the United States. Some of the research teams form collaborations. Some commercial investigators restrict their findings, hoping to patent significant genes. This is a contentious issue within the genetic research community.
Human Genome Project
Most of the university and government work, however, is published freely, and many investigators coordinate their work through the international Human Genome Project. This cooperative effort aims to write out virtually all of the human genetic code by 2003. Last year, the project decided to concentrate first on getting out a rough draft by 2001. But the work reported today was already so far advanced that the researchers went ahead to produce their final product.
This work, published by Ian Dunham of the Sanger Centre in Cambridge, England, and colleagues around the world, deals with chromosome 22. It's the next-to-smallest of the 46 human chromosomes.
Their paper lays out a sequence of 33.4 million units (called base pairs) that encode genes and other information. The sequence of the base pairs contains at least 545 genes. There are 11 small gaps. The researchers say it will take "considerable time and effort" to narrow, let alone close, those gaps - if it can be done at all.
Meanwhile, they claim that what they have published "provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome."
The greater challenge ahead
When that landscape is fully charted, geneticists will face a bigger challenge. They began with rough maps of the chromosomes' DNA structure. Now they're filling in the detail.
When that is done, they have to discover which DNA sequences are genetically potent, which can be ignored, and how the genes interact to form the complex mechanism of the human body.
The geneticists are like explorers trying to understand a densely populated alien city. Having mapped out the streets, the explorers now are detailing what lies along them - every house and building, every address, every open lot. This work will only have meaning when they find out who lives at those addresses and how they interact to form a community.
"Biology is entering a new world.... I am not sure we are prepared for the full impact," says Little. "The challenge is now to translate the new biology into tangible benefits for humanity."
(c) Copyright 1999. The Christian Science Publishing Society