1/23/01

John Sanford, News Service (650) 736-2151; e-mail: jsanford@stanford.edu

Terry Shtob, associate dean of the Continuing Studies Program (650) 725-6729; tshtob@stanford.edu

Top researchers give overview on developments in genetics

If you were among the more than 300 people who crowded into Cubberley Auditorium last weekend for "Breaking the Code: Genetics Research at Stanford," you would have learned that some human DNA sequences resemble those of baker's yeast -- a brainless, one-celled organism whose existence enters our consciousness mainly when we're baking bread or looking at the ingredients on a beer bottle.

You also would have learned that scientists are probably less than two years away from completing a final draft of the human genome, our genetic blueprint, and that zebrafish are excellent animals for genetic study.

These are just a few interrelated facets in the exploding field of genetics, in which some of the most significant and newsworthy research is happening today. Four of the world's top genetic researchers, who also are Stanford professors, gave an overview of their work and explained how their fields are helping scientists better understand, among other biological functions, evolution and disease.

The free event was sponsored by the Stanford Continuing Studies Program.

Presentations were made by Richard Myers, a professor of genetics and director of the Stanford Human Genome Center; David Botstein, chair of the Genetics Department at the School of Medicine; Luca Cavalli-Sforza, an active professor emeritus of genetics and chair of the Human Genome Organization International Committee of the Human Genome Diversity Project; and William Talbot, an assistant professor of developmental biology and director of the Stanford Zebrafish Genome Project.

Terry Shtob, associate dean of Continuing Studies, introduced the speakers and the topic. Along with creating new weapons for fighting disease, Shtob said, "there's a host of issues with both individual and policy implications that derive from genetics research and discoveries."

These include, to name just a few, issues related to the privacy and confidentiality of genetic information; genetic testing; and the use of genetic information in making reproductive decisions, she said.

"It becomes ever more important for the general public to be well educated about the science of genetics research," Shtob said.

But if there was any doubt about the public's eagerness to learn about genetics, it was likely dispelled by the large and diverse audience -- from high school students and their parents to other scientists doing work in genetics or related fields -- that showed up for the program.

The U.S. Human Genome Project was started in 1990. Working with researchers in laboratories around the world, scientists predicted it would take 15 years to completely map the human genome. But thanks to advances in technology, that date for completion likely will be 2003, if not earlier, said Myers, who presented "The Human Genome Project: Defining Our Genetic 'Parts List' and Using It to Understand Human Biology."

While the technology for determining genome sequences is the same as it was a few decades ago, machines have made the process much faster, he said. The human genome contains 3 billion base pairs of nucleotides, which are composed of a sugar, a phosphate and a nitrogenous base. Nucleotides form long, repeating strands to create those famous DNA double helixes that resemble twisted ladders.

Myers said that when he was in graduate school, the process of sequencing DNA was laborious.

"If you worked nonstop on this and really were a hard worker, you could get about 400,000 base pairs of sequence in a year," he said. But nobody could sustain that pace.

"You'd go crazy," he added. "So we really couldn't ever dream about getting 3 billion base pairs."

The audience laughed when Myers noted that some people had come up with a brainstorm of having prisoners do the sequencing. However, it takes one person with a doctorate to oversee every three to four researchers, "and there weren't enough Ph.D.s in prison, I think," Myers quipped.

The advances in machines used to sequence DNA have happened only over roughly the last five years, making the process much cheaper, faster and more accurate, he said.

The final draft of the genome will allow scientists to identify genes more effectively and try to figure out what they do. A gene is a sequence of nucleotides that determines a specific characteristic in an individual -- whether that individual is a human, chicken or lizard. One of the main goals of the genome project is to discover the DNA sequences responsible for causing disease.

Scientists already know that single-gene mutations can cause so-called Mendelian traits -- afflictions such as muscular dystrophy and Huntington's disease. Many other diseases are thought to have some genetic component, but they are more complicated because multiple genes are involved.

Indeed, understanding what DNA sequences mean is the real challenge. "Cells have no trouble understanding what's written in DNA," said Botstein, the Stanford W. Ascherman, M.D., Professor of Genetics, who presented "Genome-wide Gene Expression in Cancer." "But we don't understand. So it's like you go to Uzbekistan, and these people are speaking to each other and understanding each other, and you don't understand a thing. And that's pretty much where we are."

However, there is a "huge motivation" to understand what genes do, Botstein said. "Any of them could be useful, directly or indirectly, in dealing with disease."

Genetic research has revealed that there are several different types of breast cancer. Understanding the differences between the cancers at the level of DNA could help scientists develop drugs that are better at fighting a specific cancer.

Studying DNA also has helped scientists discover how our ancestors moved around the earth. Genetic traits can be used in tracing the migration of certain populations. Cavalli-Sforza, who presented "Genes, People and Languages: A Picture of Recent Human Evolution," noted that the genetic difference between two people in the same population is huge ­ only slightly less than the difference between two individuals in separate populations on two different continents, for example.

Two individuals from one population have 85 percent of the number of differences that are seen between any two individuals from two different populations, Cavalli-Sforza said.

He added that this is because humans have a custom of marrying "outside their usual range."

"We don't know it, but we are geared to do that," he said. "It's very wise, because otherwise we'd be full of diseases."

Cavalli-Sforza also said this fact is a great argument against playing up racial difference.

"The differences between the same races are so large that it's ridiculous to think of races as different -- or of even existing," he said.

Talbot, the final speaker in the program, analyzes genetic mutations in zebrafish, which are considered a "model organism" for such studies. He presented "Zebrafish Mutation and Functional Analysis of Vertebrate Genome." The goal is to find out what certain genes actually do, Talbot said.

Understanding the function of genes in such model organisms can help scientists find out about biological processes in humans. Researchers can generate models of genetic diseases in fish that are similar to those in humans.

Myers, however, offered a kind of disclaimer for knowledge gained through genetic research.

"Genes don't determine everything," he said. "They contribute a lot, but some variation is due to the environment, due to lots of things ­ due to things we don't even understand. So don't let any geneticist fool you into thinking genes are everything."

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By John Sanford