Eighty years ago, Texas researcher conducted X-ray experiments that won Nobel Prize

Sept. 28, 2007

In the 1920s, J.T. Patterson, the chairman of the Department of Zoology at The University of Texas at Austin, wanted to push his school into the top ranks of genetic research. So he did what Texans do, he recruited a top player for his team.

The recruit was Hermann J. Muller, a born-and-raised New Yorker who had spent most of his academic career as a student and researcher at Columbia University. He was establishing a reputation as an innovative thinker in genetics.

Muller made good on Patterson's decision by making one of the most significant discoveries at The University of Texas at Austin.

He demonstrated that radiation from X-rays would change the genetic makeup of fruit flies and that the mutations would be passed to subsequent generations. It was the first time that men had intentionally altered the genetics of another creature.

It changed understanding of the gene, revolutionized genetics research, made headlines around the world and put Texas on the science map.

In 1946, the research won the Nobel Prize for physiology or medicine. But by then Muller was long gone from Texas and was settling in to what would be a 20-year stay at Indiana University in Bloomington, Ind.

Gone to Texas

When Muller arrived in Austin, the city's population was about 35,000 and fewer than 7,000 students were enrolled at the university.

Muller took a room at a university boarding house on San Antonio Street and went to work.

Patterson and T.S. Painter, a zoologist who later became the university president, took up the fly for their research. They, Muller and others worked in a "fly room" that measured 72 feet by 24 feet. They crammed it with rows and stacks of bottles containing their experimental flies as they worked to puzzle out genetic mysteries.

Muller had long conceived the gene as the basis of life and had been laying the groundwork for his discovery for years.

He believed that genes "play a fundamental role in determining the nature of all cell substances, cell structures and cell activities," wrote Evelyn Witkin, a Rutgers University professor, in a 2000 essay about Muller.

That view was not appreciated in the 1920s, Witkin wrote, when genetics was seen as a peripheral discipline of biology.

In that context, she wrote, "Muller's early recognition of the pivotal and pervasive role of genes was a profound insight."

Earlier Muller experiments looked at the effect of temperature on mutations. In hot Texas summers, he draped wet cloths over fly containers and blew a fan on them to keep them cool.

The fly room was the center of activity for Muller and his colleagues, but it was in a smaller room that Muller made history. It was the box-like, six-foot-square room lined with lead in which the X-ray experiments were carried out.

James F. Crow, professor emeritus at the University of Wisconsin-Madison, was a graduate student at Texas in the 1930s and later became friends with Muller. He described how he conducted radiation experiments when he was at the university:

"I operated it (the X-ray machine) by turning it on and then getting out of the box until the radiation period was over—usually a half-hour or so."

Muller and the radiologist assisting him would have done their experiments in much the same way.

The Discovery

Muller's findings excited the science community when he published them in Science in July 1927. They also received much mainstream attention.

"Altered Heredity of Flies By X-Ray" was the headline in the New York Times.

The significance of Muller's discovery might get lost in the early 21st century, when scientists manipulate genes at will.

Then, however, it opened scientists' eyes to the vast possibilities of genetics.

"At that point, no one really knew how mutations were caused or what factors were involved in mutations," said David Hillis, a professor of integrative biology at The University of Texas at Austin. "So the connection between radiation and mutation was a big step."

"In a few months Muller found more mutant genes than the total from all the Drosophila labs up to that time," Crow said.

Besides the impact on the study of genetics, Muller realized the experiments showed radiation posed threats beyond the laboratory. He made that point in his first paper on the experiments.

He spoke out about the dangers of radiation on people. The Nobel Prize in 1946 increased his stature to speak out about it after atomic bombs were dropped on Nagasaki and Hiroshima in 1945.

"He understood the dangers of radiation much sooner than most people did," said Chandra Muller, his granddaughter and a professor of sociology at the university. "In our family, growing up, whenever we'd go to the dentist, my mother would get in a fight with the dentist. We couldn't have the X-rays."

"My grandfather was quite politically involved and used his position as a Nobel Laureate and an authority on the ionizing effects of radiation to speak out forcefully against nuclear arms," said Ken Muller, a neuroscientist at the Miller School of Medicine at the University of Miami. "I'd like to think that much of our concern about nuclear proliferation is in some small way due to his efforts."

Private Life

While the world celebrated Muller and his discovery, his life in Austin was coming undone.

Some of the problem could, no doubt, be attributed to Muller's contentious personality.

"He was a charismatic person, but also a very strong personality," Chandra Muller said. "He could really make some people angry."

"Other people who were biologists at the time were fairly competitive and resented the limelight he was getting. He was getting invitations to go to Europe. Probably there was a sense here that he was getting a little too big for his britches."

Considering his prickly personality, she said, "I'm guessing that he wouldn't care too much if he ruffled some feathers if he felt the people were out of line."

There also had been tension between Muller and the university over his wife, Jesse Marie Jacobs, an accomplished mathematician. She might have contributed to the mathematical rigor of Hermann Muller's papers, Chandra Muller said.

When she became pregnant with Chandra Muller's father, David, in 1923, Jesse had to resign her position in the Mathematics Department, according to department policy.

That might have added to the pressures on the Mullers.

"My grandmother had this great intellectual strength. It was a time when it was much more difficult for a woman to maintain a career and be a mother. When she got married and she lost her job she also lost her academic life in some ways and she became second to him, which must have put stress on their relationship," Chandra Muller said.

Hermann and Jesse divorced in 1932.

But while they were married and thereafter, Hermann and Jesse had strong social consciences, Chandra Muller said. Their sense of social justice had an impact on her decision to study sociology, Chandra said.

One of Hermann Muller's activities was to support an underground student newspaper called The Spark. It carried articles that called for rights for workers.

When Muller took a Guggenheim fellowship in 1932 to conduct research in Germany, it appealed to him and the university. According to the writings of Bentley Glass, a graduate student of Muller's, Patterson told Muller he would not be welcomed back. Still, Muller didn't formally resign from the university until 1936.

So ended Muller's relationship with The University of Texas at Austin.

Faded from Memory

By the time Crow, the Wisconsin professor, arrived in Austin Muller was gone.

But Muller was remembered—at least in the early years after his departure.

Wilson Stone was one of Crow's professors and Stone had been a student of Muller.

Stone, Crow said, "often spoke very respectfully of Muller, and several things in his course came directly from Muller."

Patterson, on the other hand, didn't like Muller, Crow said, "but he was always careful to say that Muller was brilliant."

Even more telling, Patterson, Painter, Stone and others carried on research that Muller had started or suggested.

Today, there are two reminders of Muller on The University of Texas at Austin campus.

One is a plaque in a room in the Biology Building, where he conducted the prize-winning experiments.

The other is the X-ray machine used in the experiments. The machine, made by the Victor X-Ray Corp. of Chicago, is housed in a display case at one of the entrances of the Molecular Biology Building.

A yellowing hand-lettered placard explains the machine's significance.

"In 1927, Professor Hermann Joseph Muller first demonstrated that X-rays caused inherited genetic changes. He used this X-ray machine for his early investigations. For this work he was awarded the Nobel Prize in Physiology and Medicine in 1946."