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A Late-Night Discovery

In 1953, Betty Geren proved her mettle as an “Iron Man.”
February 18, 2014

It was two in the morning when MIT postdoc Betty Geren called her supervisor, Francis Otto Schmitt.

Betty Geren
Betty Geren, shown here in 1955, had two years earlier captured a telling image with an electron microscope like this one.

“What the hell do you want at this time of night?” he said.

Geren told him that she had just discovered how a protective lining called myelin forms around neurons.

“My God! Bring it over tomorrow morning,” Schmitt exclaimed.

It was 1953, and molecular biology was taking off. New imaging techniques were giving scientists a detailed look at the cells and fibers of living things, and Schmitt’s lab was at the forefront. Geren, who had earned an MD in 1945, had joined the lab in 1948, hoping to address the general ignorance of cellular structure within the medical community.

“The discoveries out of that lab were flowing by the day,” Jerome Gross, a fellow postdoc in Schmitt’s group, would later recall. “Everybody would be finding new things all the time, and Frank was the presiding wizard of this whole thing.”

When Geren had told Schmitt that she wanted to figure out how myelin formed, he said, “That’s your problem—don’t worry me about it.” And so she got to work.

Schmitt had been one of the first scientists to use x-ray diffraction to study biological tissue. By directing x-ray beams at nerve fibers, muscles, collagen, and other biological building blocks, he and fellow MIT professor Richard Bear had studied the patterns of deflected photons to deduce the structures of the samples.

One of these patterns in a nerve fiber cross-section caught Geren’s attention. Schmitt and his colleagues had already determined that the diffraction pattern indicated a concentric layering of fat and protein in the myelin sheath around the nerve’s central axis, but they didn’t know how the layering formed.

Geren decided to find out using the lab’s electron microscope. The newly developed instrument produced images of much finer resolution than x-ray diffraction, because the wavelengths of electrons are much smaller than those of x-ray photons. And just as with x-ray diffraction, Schmitt’s lab was one of the first to use it on biological tissue.

The electron microscope wasn’t always easy to deal with in those early days, so Geren spent a lot of time looking at fuzzy and unusable images of nerve fiber cross-sections that she had extracted from chick embryos. But that night in her lab at the Children’s Cancer Research Foundation in Boston, she got a good shot, and everything became clear. The concentric layers actually spiraled out from the center of the nerve fiber. Geren realized that after the neuron formed, fatty protective cells engulfed it and wrapped around its circumference multiple times.

Other scientists soon confirmed this “jelly roll” idea. Geren’s discovery showed that myelin was generated by dynamic cellular interaction. And understanding how it forms would later prove crucial for scientists trying to prevent and treat diseases like multiple sclerosis.

Shortly after her discovery, Geren got a letter from Herbert Gasser, a Nobel Prize–winning physiologist and one of her mentors at Washington University, where she’d earned her MD. Written in Latin, the letter read, “Old charming fellow, you have hit the nail on the head.” Indeed, the paper on her findings has been cited more than 500 times. And today Geren, who is 91 and goes by the name Betty Uzman, lives on a farm in Arkansas, where she keeps Gasser’s framed letter on the wall of her office.

About 30 years after her breakthrough, Carroll Williams, who at the time was a biology professor at Harvard University, said that Geren’s work would be one of the defining achievements of the Schmitt lab. “That probably is the one investigation that topped them all, because it came right out of left field,” he said. “That was really a smashing discovery.”

To single out Geren’s work from the lab’s many accomplishments is high praise. “We were doing better electron microscopy than anybody in the world at that time,” Gross later said. In fact, Schmitt called his group the “Iron Men of MIT” because it captured the swagger of such an eager group of young scientists.

The name “reflected a sort of swashbuckling attitude and the stamina to talk science all day and during dinner, then drink and talk science all night, at least until one or two the next morning,” Geren later remembered. “And then be up and fresh, and repeat the same schedule the next day.”

Perhaps that explains why Geren’s call to Schmitt came well after midnight.

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