Blum, "Scientists in Open War over "Neutral Theory"
of Genetics," Sacramento Bee, March 16, 1992, p. A1.
-- When geneticists came up with the term "neutral" theory to explain some of the finer details of evolution they made a mistake. They should have called it "open hostility" theory. Or maybe even "total warfare" theory.
Over this one idea - an elegant explanation of how living things differ at the molecular level - researchers have started shouting at each other during cocktail parties. Scientists have boycotted confer ences because members of the opposition were also speaking.
And John Gillespie, a population geneticist at the University of California, Davis, has been given an unusual nickname. Just last month, Gillespie published a book that contains a tough, sophisticated attack on the theory. An eminent Japanese scholar who takes the opposite view now refers to Gillespie as "the evil scientist from America."
Scientists say that the furious battles over molecular genetics may yet help define how species on Earth took shape, tracking in better detail the evolution of life. The science may also yield new insights into inherited diseases, such as muscular dystrophy or cystic fibrosis.
And, if nothing else, it is a field of study that will never be dull.
"It's the greatest topic in the world," says William Provine, a science historian from Cornell University, who is researching the international battles over the neutral theory. "I can't even begin to tell you how much fun it is. People just fight like crazy."
The neutral-theory wars began in 1968, almost as soon as the theory was proposed. It was born out of the increasing ability of biologists to peer into the body's smaller structures, stripping apart proteins to see the amino acids that build them. Scientists were astonished at the amount of variation at the molecular level.
For instance, the red-rich protein in blood, hemoglobin, might seem to be identical from person to person, species to species. But it isn't.
Taken down to its basics, there are odd little flickers in the protein shapes. At first look, it was almost shocking to see the differences, as if the body was fundamentally unstable, wildly prone to change.
The neutral theory said, in effect - calm down.
Its fundamental idea was that all those little dings and gaps in the protein structures were "neutral" - they really didn't mean anything. Hemoglobins might look different under the microscope, but they all still serve the same purpose, to carry oxygen through the bloodstream.
The theory suggested that the tiny variations were a result of the natural genetic drift, simply that the instructions carried within genes didn't always repeat themselves perfectly. That scientists were seeing the results of a bunch of meaningless genetic typos.
"It was a radical idea," Gillespie said. "The controversy started immediately."
The followers of Charles Darwin, which meant basically everyone in biology, reacted with outrage. Under Darwin's famed theory every change matters, natural variations are essential to evolution.
Darwin argued that sometimes variations would provide advantages to an animal. Those with the advantage might survive better than those without; the new trait would be passed on; and slowly the species would take a new shape.
Biologists assume, for instance, that the long neck of the giraffe evolved in just such a way, starting with a small, natural variation, an extra stretch, which allowed some animals to better reach leaves. As the longer-necked animals ate better and lived longer, that variation was passed on - and improved - through generations. The process is called natural selection - or sometimes, survival of the fittest.
But the neutral theory said that at the fine molecular level, especially after millions of years of evolution, natural selection was less important, that tiny changes could come and go without effect.
When biologists Thomas Jukes, of the University of California, Berkeley, and the late Jack King, of University of California, Santa Barbara, published their arguments for neutrality in 1969, they called it "Non-Darwinian Evolution" - and then prepared for the fight.
"Did we ever catch flak," Jukes says, recalling occasions when outraged geneticists began screaming at him during parties. "Our article was like blasphemy."
If Jukes and King began the fight in this country, the most powerful proponent of the neutral theory on the international scene was Matoo Kimura, director of Japan's National Institute of Genetics. Kimura began publishing on the theory in 1968. He has worked tirelessly on its behalf since, and he considers it his own.
"I published one year before Jukes did," he said in a telephone interview. "But even I had been brainwashed by the natural selectionists. It was hard for me to emotionally accept my own theory." In 1983, having overcome reservations, he published a book explaining the theory and its importance.
That was the beginning of John Gillespie's problems with Kimura. He reviewed the Japanese scientist's book for the prestigious journal Science. Gillespie was annoyed by the tone of Kimura's book: "He devoted an entire chapter to telling us that he had saved us from ourselves." The UC Davis scientist complained about it in the review.
"He said Kimura was a glory hog, and he scolded him for it in public," said Cornell's Provine. "In Japanese society, that's very insulting."
Even Gillespie says now that he wishes he had left that one paragraph out of the review: "If I had, my whole life would be different."
That was brought dramatically home to him in 1988 when he attended an international genetics conference in Japan. He was barred from the Japanese National Institute of Genetics, forced instead to meet colleagues privately. "It was stupid," Gillespie says.
To that, Kimura replies that it was time-saving: "I wouldn't waste my time meeting with a scholar whose research is so trivial."
But the disagreement has not stopped Gillespie from taking on the neutral theory. "For years, John almost single-handedly carried the banner for natural selection," says Martin Kreitman, an experimental geneticist from the University of Chicago. Kreitman's own work, tinkering with the genes of fruit flies, has convinced him that Kimura is wrong, that natural selection does exert pressures, even at the tiny molecular level.
Gillespie's newly published book, "The Causes of Molecular Evolution," is a potent argument for rethinking the neutral theory: "Not everyone would agree with this, but I think this is the most serious challenge to the neutral theory," he said.
The theory predicts that genetic drift will occur at a steady rate, so constant that by measuring DNA differences between two species, one can calculate how long ago they separated on the evolutionary tree. For instance, based on the tiny variation between humans and chimpanzees, scientists believe the two species separated about 5 million years ago.
That steady tick of variation is known as the "molecular clock." But Gillespie says that new technology - allowing better pictures of proteins and genetic material - has shown clearly that the variation is not steady, that there are sudden rapid bursts of change. The neutral theory fails to allow, as Gillespie does in his work, for some real complications, such as a changing environment.
Geneticist Francisco Ayala, of the University of California, Irvine, says the neutral theory rose in power in part because it was so simple - clean mathematical models could be built out of it. "The people who introduced it have fallen in love with their own beautiful math," Ayala said. "They've forgotten that it isn't necessarily reality."
But Ayala also thinks neutrality will remain important. He suspects that it will simply become a smaller part of the story, with more allowance for natural selection. For instance, he said, the molecular clock concept still should hold: "The time spans involved - 500 million years, 700 million years - are so huge that a little wobble doesn't mean that much."
Neither Jukes nor Kimura concedes even that much. Kimura says many have tried to knock down the theory and failed. He insists it will stand. Gillespie tried recently to talk to Kimura about their differences. He approached the scholar during a conference in Wisconsin, while covering his name tag with a stack of books. He managed to compliment Kimura on a speech he had given before the other researcher saw his name tag.Kimura turned and walked away.
This page was assembled by Michael Dietrich. It was updated on 26 March 2001.