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Academia / Science

‘For him, it was an adventure:’ Pittsburgh inventor Alan Waggoner leaves behind a legacy of practical discovery

Colleagues remember the long-tenured CMU professor, who helped revolutionize microscopy with CyDye, as intellectually omnivorous — and somewhat unconventional.

Alan Waggoner, professor and inventor of CyDyes (Courtesy Carnegie Mellon University)
The local legacy of Alan Waggoner, a longtime Carnegie Mellon University professor who died at 82 this May, stretches far beyond his place as a top authority in the field of cellular microscopy.

He not only made scientific breakthroughs, but also helped pioneer the idea that for lab discoveries to be truly impactful, they had to be commercialized and put to use in real-world applications. 

A resume of his achievements doesn’t get at the importance of his work nor the respect he held among his colleagues, several former collaborators told Technical.ly. 

“Alan was a tremendous human being. He was compassionate, inclusive and kind to everyone,” said D. Lansing Taylor, professor and director of the University of Pittsburgh Drug Discovery Institute. “That was his personality and style, but that was coupled with being a brilliant and inquisitive scientist, teacher and entrepreneur.”

Waggoner’s best known invention, called CyDye, helped revolutionize fluorescence microscopy. That’s the process by which cells are illuminated with bright light after being exposed to synthetic dyes, which allows scientists to track individual molecules within cells, mainly by labeling proteins and genetic material.

He didn’t like doing what others did. For him, it was an adventure.Christopher Szent-Gyorgyi Chemist who worked with Waggoner

CyDye, along with other fluorescent dyes, led to major advancements in biomedical research and health care.

Surgeons have used them in rare instances to remove cancerous tumors, scientists used them to help complete the Human Genome Project, and biologists now regularly wield them to “explore almost any question in the life sciences,” per Pitt Med magazine. 

Collaborators of Waggoner’s remember a kind and generous colleague who was intellectually omnivorous and somewhat unconventional, they told Technical.ly. Known to be casual in the office, he would sometimes walk around in his stocking feet or lie on the floor of his office. 

CMU research background helped build startups

Waggoner came to Pittsburgh in 1982 to help get CMU’s new Center for Fluorescence Research off the ground. Taylor, a cofounder of the fluorescence center, said he knew he needed Waggoner from the start. 

“I realized this wouldn’t work without the world’s best fluorescent probe chemist, and that was Alan Waggoner,” said Taylor.

While working at CMU, Waggoner developed and patented a new type of cyanine dye, called CyDye, and in 1992 left the university to co-found the company Biological Detection Systems, Inc with Taylor. BDS Inc. continued development of CyDyes and built a research imaging platform, said Taylor.

When the company was sold to Amersham PLC, Waggoner went along. But he returned to CMU in 1999 to direct the Molecular Biosensor and Imaging Center (MBIC). More recently, he helped establish Sharp Edge Labs, now Sharp Therapeutics, Inc., a company that develops treatments for genetic diseases. 

CyDye changed how scientists capture images of cells

CyDyes are Waggoner’s biggest claim to fame, according to Christopher Szent-Gyorgyi, a visiting researcher in CMU’s chemistry department who worked with Waggoner at MBIC. These dyes offer critical advantages that scientists rely on, he said. 

They are highly water soluble, essential when most of the cell is composed of water. They also reliably change color when hit with light, or “excited,” said Szent-Gyorgyi. CyDye makes it easier for scientists to label and track tiny proteins and genetic material within the cell. Though small, these molecules are vital in understanding why and how cells work the way they do.

The dyes are also fairly easy for chemists to work with, compared to other synthetic dyes. New colors can be synthesized merely by adding two carbon atoms and two hydrogen atoms, according to Bruce Armitage, professor and head of the Chemistry Department at CMU.

CyDyes stay fluorescent for longer periods of time than most other dyes, too. That makes the molecules they are attached to visible for an extended time and allows researchers to take high-quality images of the cells, Armitage said.

Researchers have used CyDyes for breakthroughs in the fields of flow cytometry, genomics and the study of antibodies. These have in turn led to advances in disease diagnosis and treatment. 

Waggoner’s legacy of pragmatic, helpful results

It was the drive to create pragmatic applications for discoveries in the lab that led Waggoner to start companies to get their work into the world, according to Taylor.  

He was doing that almost from the beginning. In 1971, Waggoner worked with a team of neuroscientists at Yale University trying to visualize electrical impulses in squid giant axons, the largest known nerve cells.

“The brain works on electrical events, and we wanted to see if we could measure the electrical activity of cells using optics instead of electrodes,” said Brian Salzberg, one of the neuroscientists, and now a professor of neuroscience and physiology at the Perelman School of Medicine at the University of Pennsylvania and vice-chair of the Department of Neuroscience.

Waggoner synthesized dozens of compounds for the team. In the end, a compound the team acquired from Eastman Kodak was the one that worked, but Salzberg said Waggoner’s participation was essential to the project’s success.

Through it all, his colleagues said, Waggoner wanted his work in the lab to translate to something practical and useful. 

“He didn’t like doing what others did,” Szent-Gyorgyi said. “For him, it was an adventure.”

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