Revolution in Health Care Promised, but Decades of Work Lie Ahead

Now, the hard work begins.

For all the celebration Monday over deciphering “The Book of Life”--the genetic information that controls most of what goes on in the human body--scientists know that they will need decades to fully comprehend the text.

In the end, they promise a new era of medicine with new treatments for nearly every medical ailment--treatments that come from tweaking the genes that tell cells how to go about the work of daily life.

Instead of poisoning a cancer patient with chemotherapy, doctors might simply switch on the genes inside tumor cells that tell them it is time to die. Instead of giving clotting factors to hemophiliacs, doctors might fix a patient’s flawed genes as though changing a broken gasket on a car. Dozens of other ailments might be eased or cured as researchers invent drugs that tell certain genes to work harder in the body, or to stop working altogether.

“This genome sequence is really going to create revolutionary change in everything associated with human health,” said Richard Young, a gene researcher and biology professor at the Massachusetts Institute of Technology. “It will range from a better understanding of basic biology to new diagnostic tests for the major health problems to new cures for disease.”

But getting there will be a massive project. Today, scientists cannot even agree on how many genes exist in humans, with guesses ranging from 38,000 to 140,000.

The “Book of Life” contains the chemical sequence of DNA, the famed double helix that resides in almost every human cell. Genes are small segments of DNA that contain the recipe for specific proteins, which in turn handle the body’s basic chores, such as helping to metabolize food into energy or to signal to another cell.

Wayward genes can produce flawed proteins that cause disease. Accordingly, many cures of the future will not seek to change the genes themselves but instead try to intercept the bad proteins before they can do any damage.

Devising those cures is the work of the next 20 or 30 years. But already, the benefits of genetic research are finding their way into doctors’ offices.

Julie Louviere had beaten breast cancer, but three years ago, she found herself hospitalized again with cancer of the bones and liver. As it turned out, the Memphis mother of two was one of the 25% to 30% of breast cancer patients with an overactive gene, called the HER2 gene, that was spurring her cancer on by making too much of a growth protein.

A new drug called Herceptin inhibits the extra protein. While not a panacea, the drug can extend the life of many patients.

“I’ve had two extra years of my life because of this,” said Louviere, 36, a former triathlete. She said that 18 months of Herceptin, combined with chemotherapy, have shrunk or eliminated many of her liver tumors. “I’m living proof that this can work,” she said.

There are bound to be more successes like Herceptin, which was developed before scientists had much of the human genome in hand. Now researchers hope to find new drugs merely by scanning the text of DNA.

Amgen Inc. has already done just that. Researcher William Boyle trolled electronically through Amgen’s private database of mouse DNA and found an interesting gene.

To find out the gene’s function, Amgen bred mice with extra copies of it. The result was mice with very dense bones. And when Amgen bred mice that lacked the gene, the result was thin, brittle bones.

“With very little hands-on lab work, we were able to find a gene that leads to higher bone density,” Boyle said. Amgen found an analogous human gene and is testing a drug on humans that is based on the gene protein. It could help patients whose bones are deteriorating from age or cancer treatments.

Studying genes is also showing scientists the limits of their traditional tools--for example, the microscope. Specialists still label some kinds of cancer--diffuse-cell cancer, cleft-cell cancer--according to what they see in a microscope.

But by examining genes, researchers have made a startling discovery: What looks like one type of cancer under the microscope is actually a whole family of diseases, each of which probably requires a different treatment strategy.

Of the 25,000 Americans diagnosed each year with a common form of non-Hodgkin’s lymphoma, for example, about 10,000 respond well to chemotherapy and survive. The other 15,000 will suffer through the painful treatment, only to die.

Now researchers think they know why. Dr. Patrick Brown of Stanford University and Dr. Lou Staudt of the National Cancer Institute have shown that the genes active in some patients’ tumors are different from those in other patients diagnosed with the same form of lymphoma.

By analyzing genes, doctors soon will be able to tell which patients with this type of lymphoma are likely to benefit from chemotherapy and which should receive some other treatment.

Understanding human genes “frees us from the microscope,” said Dr. Richard Klausner, director of the National Cancer Institute. “It frees us to look at the actual mechanism of disease and not just at the consequence of that mechanism, the symptoms in the body or what a cell looks like, as we do now. We can look right into the machinery.”

Studying which genes are at work in an illness could even help doctors diagnose infectious diseases. “When you have an infection, or just feel terrible, it’s not even evident that it is an infection. It could just be bad food,” said Young, the MIT professor, who is also a researcher at the Whitehead Institute for Biomedical Research in Cambridge, Mass.

Recently, Young has shown that it may be possible to figure out what infection is at work. He is studying macrophages, the free-floating cells that are the first line of defense against disease-causing agents. The genes active within macrophages vary, depending on what kind of intruder they encounter.

Young says he has been able to distinguish a macrophage fighting tuberculosis from one fighting HIV, influenza or any of seven other infections. Ultimately, he said, a clear diagnosis will require doctors to study the genes in other cells involved in the immune response, as well as those in macrophages.

Many of the breakthroughs came before the text of human DNA was in hand. But the pace of the work has accelerated over the last two years as the chain of 3.1 billion chemical units in DNA has become known. In recent weeks, scientists in the publicly funded Human Genome Project have posted their work on the Internet at the rate of 10,000 units a minute.

How fast will the research go? Dr. Francis Collins, who leads the largely public effort to sequence human DNA, predicted that within 10 years, doctors will be able to tell patients whether they have genes that make them susceptible to such diseases as high blood pressure, diabetes and heart disease. “That kind of predictive information could be quite useful to you . . . because it would allow you to practice individualized preventive medicine focusing on the things that are most important for your own health,” he said.

In 15 to 20 years, he predicted, it will be common for doctors to prescribe drugs targeted directly at genes and their protein products.

(BEGIN TEXT OF INFOBOX / INFOGRAPHIC)

Genome’s Potential Uses

Improved diagnosis of disease; earlier detection of genetic predisposition to disease.

*

Gene therapy: repairing defective genes with healthy ones.

*

New drugs from identifiying genes, the proteins they produce and their role in disease.

*

How the DNA directs the cell: 1. Instructions from the DNA code in the chromosomes are “read” by RNA, or ribonucleic acid. 2. RNA leaves the nucleus and links up with ribosomes, which are protein-making units within the cell. 3. The RNA and ribo-somes interact to assemble amino acids based on the instruction from the DNA. code. 4. Amino acids are folded into proteins that direct the cell’s function.

*

Sources: “From So Simple a Beginning”; Ultimate Visual Dictionary 2000; Human Genome Project