But of course, no flash flood of new treatments resulted. In fact, the drug-development pipelines of many pharmaceutical companies got skinnier, not fatter. And stock prices of genomic companies tanked.
The main reason: Biology is complicated. Knowing the genetic code of humanity is only one step toward understanding what each gene does, how genes are involved in disease, and what treatments work best. So after the human genome project was over, the National Institutes of Health held a series of meetings to figure out what the next steps should be. "We put together a vision of the future on the advice of 600 or so of the best and brightest minds we could convince to come to NIH," says Dr. Francis S. Collins, director of the National Institute for Human Genome Research.
"FANTASTIC FOUNDATION." The result of these deliberations was a road map that charted a research path that should finally lead to all the medical advances promised in those original headlines.
Take one component, the HapMap project. "The human genome sequence is a fantastic foundation," Collins explains. But to know why people get diseases, "that 0.1% of DNA that differs between people is something you want to understand in great detail." Why, for instance, does one smoker get lung cancer when three others don't? Or why do some people come down with heart disease when others -- with similar diets and lifestyles --remain healthy?
The reason often lies in those very few genetic differences between people. Of the 3 billion "letters" in the human genome, about 10 million are believed to vary. In a gene 5,000 letters long, Joe might have a letter "T" at position 491, while Mary has a letter "G" at the same spot. The difference could explain why Joe has higher blood pressure than Mary does.
STAGGERING SLEUTHING. Once researchers find the genetic variation that increases the risk for, say, diabetes, they also gain a better picture of the biological pathways underlying the disease. That could lead to novel treatments.
But how do researchers find those genetic variations? One way is to collect samples from 1,000 people with a disease and 1,000 people without a disease. Then, you look at all 10 million of the genetic variations in each person, searching for those variants that are associated with the disease. But that would be a staggering amount of genetic sleuthing.
The HapMap offers a shortcut. It turns out that some of these DNA variants are almost always found together on a chromosone. So if you discover what one of them is, then you will know what several others are as well. Groups of linked variations are called haplotypes. The government has been funding researchers to map those haplotypes -- hence the name HapMap.
NEW WINDOW. The scientists have learned that instead of having to search 10 million individual variants, they need only look at a set of perhaps a 250,000. That makes a huge difference -- and the HapMap is leading to new discoveries.
Earlier this year, three separate teams of researchers simultaneously reported that they had used HapMap data to find a genetic variation linked to macular degeneration, the most common cause of blindness in the elderly. People with one copy of the variation have a two- to fourfold increase in risk of the disease. People with two copies have a five- to sevenfold increase.
What's especially interesting is that the gene in which the variation is found makes a key protein in the immune system. Not only does that provide a whole new window into how this eye disease occurs but it also offers a possible new target for drugs.
TARGET PRACTICE. That's one strategy. The NIH is also backing another innovative approach to understanding biology and finding new targets for drugs. It's setting up several centers around the country that will have the ability to test 500,000 chemicals a day in so-called biological assays. Researchers around the county will bring every biological test that they can dream up to one of these facilities. The expectation is that some of the chemicals tested will "hit" the target. The chemical could then be used as a probe to understand a particular biological pathway or as the basis for a new drug.
Drugs now on the market target less than 500 proteins or genes in the human body. But some 30,000 genes make proteins, and several proteins per gene. Plus, stretches of DNA don't make proteins but clearly have important biological roles, such as regulating other genes. So the universe of potential targets is vast -- at least 100 times greater than what the pharmaceutical industry has tapped so far.
Industry will explore a fraction of those new targets, since most have no obvious connection with disease. But academic scientists are typically interested in understanding biology, not finding drugs. The expectation, therefore, is that the academic researchers will use the NIH-funded screening centers to explore thousands of poorly understood biological pathways. And as usually happens during the pursuit of basic research, some of those pathways may have unexpected utility, offering whole new ways of tackling disease.
DISCOVERIES VIA CONNECTIONS. What's more, the NIH plans to put all the information gleaned from these tests into public databases, with a network of links to all the relevant scientific papers. So an obscure paper on some fruit fly gene might immediately be linked to information on the analogous human gene and all the chemicals that are known to affect the gene and the pathway it's in.
That way, it will be possible for scientists around the world to mine this vast collection of data. Indeed, Dr. David Lipman, director of the National Center for Biotechnology Information (NCBI) (a division of the National Library of Medicine) has a vision for a new type of research, where scientists will be able to make new discoveries simply by making new connections in existing data. Already, says Lipman, "such serendipitous discoveries are being made using freely available tools and online data. There are real tangible results."
In other projects, scientists are planning to read the entire genetic codes of many types of cancers and to disable every gene in the mouse to try to better figure out what each gene does.
BUILDING BLOCKS. Ultimately, the expectation is that people will be able to have their genomes sequenced -- and know what their risks of developing certain diseases are. By then, we should know enough to take the right steps to prevent those diseases from occurring.
It won't happen for years or even decades. But just as biotechnology itself is beginning to pay off 30 years after the foundations were first laid, these projects that are building upon the reading of the human genome should eventually lead to an even greater transformation of medicine. By John Carey in Washington