"Natural selection always has, and probably always will, select out such a catastrophic defect. If it did nothing good, you'd expect it to be gone forever by now. But it's not; it's amazingly common. One in every 20 Caucasians carries it.
"So there's a good possibility that this gene is involved in something beneficial that we don't know about. Personally, I believe the disease is a side effect of something else, something important, that we haven't found out about yet.
"It seems obvious at first--just get rid of this horrible defective gene--but I'm worried that we won't have the insight to manage such things wisely."
For the power to reach into human genes and change them "is not that far off," Wasmuth says. "It can be done in mice right now. If it can be done in mice, it won't be too long before it can be done in humans. Ethically and legally it's not going to happen for a long time, but technically it could be done fairly soon."
These are relatively new worries for Wasmuth, he concedes. "When I first started, I hadn't even considered it."
He started in Greenville, a small farming community in southern Illinois. Born in 1946 to a grocer and a registered nurse, he developed a passion in high school for sports and science. They turned out to have more in common than he thought.
"In science, being competitive makes a lot of difference," he says. "It's a competitive world, more than most. No one ever remembers who made a discovery second."
No one in Wasmuth's family had ever earned a college degree. "The people I knew there either didn't go to college and stayed in town or they went to college and didn't come back."
Wasmuth joined the latter group and set off for Southern Illinois University with medical school in mind. The path led through Purdue University and the Baylor College of Medicine, where a genetics professor took Wasmuth under his wing. Not surprisingly, medical school was eclipsed by an increasing interest in the clinical aspects of genetics, Wasmuth says.
By then he had married Judy Schwierjohn, "a real, bona fide German. Her parents were farmers in Illinois, and we had been high school sweethearts." They have been married 30 years and now live in a large house overlooking Lake Mission Viejo. His wife works for a firm that auctions real estate.
His introduction to genetics at Baylor changed his life, Wasmuth says. Until then he had envisioned a teaching career "at some reasonably sized college. It would be a nice, sedate way to make a living, I thought. But the more I got into genetics, the more I liked research, and that means a high-powered university."
In 1977, Wasmuth was hired at UC Irvine to teach biochemistry to first-year medical students and to conduct the research of his choosing. "I'm really not sure how I wound up here, but once I got here, everything really sort of fell into place. UCI was a good career move. There was not much genetics being done here."
Wasmuth began basic genetics research, shifting in the 1980s to intensive research into gene defects that cause disease. In 1993, he established UCI as one of the 16 universities with a Human Genome Center, a part of the National Institutes of Health's long-term effort to map the location and purpose of every human gene.
It's a monumental task, Wasmuth says, "probably the most difficult yet most interesting thing in biology." It appeals to him, he says, for the same reason mystery stories appeal to him. "You have clues all along the way, and you really have to think about them. To me, this is just the biggest mystery of all."
Gene-mapping is literally code-breaking, for the string of molecules in a gene is eerily like computer code. No one knows the method this genetic code uses to instruct its cell in how to form and what to do, but the code itself can be read. Laboratory equipment can take sections of genes and print out their sequences as a string of letters.
The genetic alphabet has only four letters--A, C, G and T--each representing one of the four kinds of coding molecules. The sequence carries the meaning. Just as ..- means \o7 U \f7 but -.. means \o7 D \f7 in Morse code, A-T-G means this is the beginning of a gene sequence but T-A-A means this is the end. What lies between may be a string of 1,000 molecules, but it may also be as many as 1 million.
There are 3 billion coding molecules in a complete set of human genes, and just one misplaced molecule can cause immense changes in human development. Researchers like Wasmuth search for that molecule by meticulously comparing the genes of afflicted people with the genes of normal people. Find the sequence in all the afflicted that is never seen in the normal, and you've solved the mystery.
You have also laid a foundation for future research, for if your gene causes, say, dwarfism, it must be in a gene that affects bone growth. Those seeking the genes for other genetically induced bone disorders are sure to search that region once your results are published.