Bud Ryan: a role model for faculty, students, grandkids

Through the crackle and static, a 1940s radio tale unfolds. The intrepid scientist hacks through tangled jungle in search of treasure. The object of his quest? Plant life containing unknown chemicals that could benefit mankind.

A young Bud Ryan, listening in rapt wonder, is inspired.

These many decades later, the program title, “Better Things for Better Living Through Chemistry,” has proved the theme of Ryan’s life’s work. His biochemical research and teaching have inspired work and products to (just for starters) enhance the environment, improve human nutrition and block cancerous tumor production.

In honor of his achievements,

Washington
State
University
will confer its highest award — an honorary degree — upon
Clarence A. “Bud” Ryan at spring commencement, 8 a.m. Saturday, May 7, at Beasley Coliseum. He will receive an honorary doctor of science degree.

The university has not awarded an honorary doctorate since 1995. It has awarded only four such degrees in the last half century. (For more on honorary degrees, please see http://www.wsu.edu/president/committees/honorary-granted.html)

“It is rare for

Washington
State
University
to award the honorary doctorate degree and still more rare for us to award it to one of our colleagues,” said WSU President
V. Lane Rawlins. “Bud has made such an impact on the world and is so much a part of the fabric of WSU that this honor seems especially appropriate.”

The degree recognizes individuals who have achieved eminence in their fields and whose literary, artistic or scientific contribution enhances the intellectual climate at the university.

“WSU is well known around the world among scientists and educated people, especially in the area of plant research, because of the accomplishments of Clarence A. Ryan,” said
College of
Sciences Dean
Michael Griswold
and

College of
Agricultural
, Human and Natural Resource Sciences Dean
R. James Cook in their letter nominating Ryan for the award.

Ryan is the Charlotte Y. Martin Distinguished Professor of Biochemistry and Plant Physiology at WSU. He was the first WSU faculty member to be admitted to the National Academy of Sciences. Several of his research articles have been ranked among the most cited in their discipline.

With all these accomplishments, Ryan is quick to recognize the mix of contributions that through the years yielded such achievement. Among them, he credits mentors, colleagues, hard work, patience, perseverance and what could be called serendipity, epiphany or even just luck.

“It has been a team effort,” he says, explaining that he sometimes thinks in sports metaphors — a remnant of his undergraduate days playing basketball for the Carroll College Fighting Saints in Helena, Mont. “On a team, it all works together.”

He had a good coach early on — Sister Evangelista. A teacher at his Catholic high school, she encouraged students to use their minds and solve problems. “She always liked to talk about ‘mental gymnastics,’ ” Ryan says, not mentioning that hers was also a sports comparison. “She had a great science class, and that really got me interested.”

Later, an enthusiastic college friend took it upon herself to make an appointment for Ryan to talk to the chemistry chair at

Montana
State
University
. The chair offered him a job that got him through graduate school there. He pursued post-doctoral work at
Oregon
State
University and then was hired by H.K. Balls at the USDA lab in

Albany,
Calif.

Balls had become famous in the 1940s for demonstrating an active site on an enzyme; that is, for identifying the location on the enzyme where the chemical reaction occurs as the enzyme digests protein.

Before agreeing to take on Ryan at his lab, Balls asked the young man if he were lucky. On the spot and having no idea how to answer, Ryan very honestly said, “Dr. Balls, if you hire me, I’m lucky, and if you don’t, I’m unlucky.” Balls slapped his knee and hired Ryan the next day.

“What happened at that lab changed my life,” Ryan says. “That’s when I really started my science.”

Although Balls’ research focused on animal proteinase enzymes and substances that inhibit them, an unrelated journal article of the time prompted Ryan to look for proteinase inhibitors in plants — specifically potatoes. When he found the lab was out of the tubers, he ran across the street to get three russets from the neighborhood grocer.

After three months of trying to isolate the enzyme inhibitor, Ryan was in the lab at 6:30 a.m. As the mixture in his test tube cleared, the early morning sun glinted off a sheen in the tube. The microscope revealed “beautiful hexagonal crystals,” Ryan recalls. They were protein crystals, and they were the enzyme inhibitor.

Prior to this, proteinase inhibitors had been known to be storage proteins in soybean seeds that could inhibit enzyme action. But the one Ryan isolated from potatoes was from vegetable (not seed) tissue. This opened a new field of investigation into the role of proteinase inhibitors, Ryan says.

Based on this work, Ryan obtained grant funding from the National Institutes of Health to pay his salary for 10 years. But he needed a university where he could continue his science. WSU was that university. In 1964, Ryan came to

Pullman
to begin work on the proteinase inhibitor mechanism. He was WSU’s only biochemist totally dedicated to plant research.

With patience, perseverance and team effort, the work progressed incrementally. Ryan found the inhibitor not just in the potato tuber, but in the leaves. Then he found it in leaves of tomato plants (closely related to the potato).

After noticing more inhibitor in plants near open windows, Ryan speculated that damage from insects or microorganisms entering the window caused the plants to respond. More testing found this was the case. What’s more, the leaf damage caused the plant to produce inhibitor throughout, and not just at the site of damage.

“That was a huge discovery,” Ryan says. “That was the first demonstration that a plant can send signals throughout the plant from wounded leaves to unwounded, telling them the plant is under attack and to make the proteinase inhibitors as defense chemicals.”

These defense chemicals inhibit enzymes the insects use to digest protein. If they can’t digest what they’re eating, they get sick and stop eating. The plant defends itself.

In 1972, Ryan’s team reported these accumulated findings in the journal Science. Then they started looking for the component that turned on the inhibitor.

They thought they’d found it in a piece of cell wall, but suffered a setback a year later when a group in Scotland showed that these fragments didn’t move throughout the plant. After working through the 1970s and 1980s, Ryan’s lead technician
Greg Pearce in 1992 isolated a peptide (an amino-acid compound) that signaled the inhibitor. They called the peptide systemin.

“Plants had never been known before to have a peptide hormone regulate anything,” Ryan says. “Animals use polypeptide hormones for just about everything — insulin, pain, development, endorphins for happiness. It was always thought plants were entirely different from animals in regulating genes. So this was really quite new.

“It’s like hitting a home run when you see these things happen,” Ryan says. “I mean, you realize nobody’s ever seen this before.”

Within a year, Ryan’s lab also discovered the signaling system that the hormone regulated. “It causes a cascade of reactions that end up activating the genes after many, many, many steps,” he says. “So systemin was just the first step in a whole series of reactions leading to a defense response.”

And systemin spawned a whole series of work by Ryan’s team and other scientists on how polypeptide signals might be involved in regulating plant genes. Today, Ryan says, there are about 20 identified hormones in plants that regulate such things as defense, development, reproduction and undoubtedly many other processes.

In 2001, Ryan’s lab identified the initial steps of the inhibitor-enzyme pathway by isolating the systemin receptor, the location on the cells where systemin makes contact. He had been working toward this goal at WSU more than 35 years.

“I try to tell young people that research is incremental,” he says. “There are many small advances. Sometimes there’s a quantum leap, but even that comes only because of each small advance.”

His research today is focusing on finding polypeptide hormones in other plant species that might also act as signals for defense.

“Now that we have the peptides and the receptor identified, we can think about using their genes to improve the ability of plants to defend against insects and pathogens,” Ryan says. That can be done by selective breeding or genetic engineering.

Ryan believes in the future of genetic engineering. “It offers wonderful promise if it’s done correctly,” he says. He hasn’t encountered criticism for his work, he adds, probably because none of the genes he works with are as yet in the field in the

U.S.

Ryan also believes in certain qualities — employed by himself and those he’s worked with — that have made his research a success. Commitment is one of these. WSU colleges, deans and presidents through the years have committed time, money, people, support and space to his work. The top floor of Clark Hall, newly built in the early 1970s, was dedicated to the Institute for Biological Chemistry (IBC), which he helped found in 1971.

He appreciates taxpayer commitment to higher education. “My teaching and research at this university have been paid for by the state’s and nation’s citizens,” Ryan says. “It has really been a privilege, and I feel an obligation not to waste the opportunity they’ve given me.”

And, sounding a bit like a coach, he encourages commitment on the part of his WSU colleagues — in their teaching, research and especially in the sometimes discouraging area of getting grant money.

“Grant money comes from your success,” Ryan says, so you must be committed to doing excellent work. Grants are extremely competitive, he says, so you must be committed to preparing a standout application. “You’ve got to go back, review what you’ve done, focus on where you want to go. It’s a terrific exercise in focusing, like giving a good lecture. You’ve got to get in all the information, but it must be structured and concise.

“It’s a learning experience, as well as a chore.” But even the chore must be rewarding, he says. “If getting grants and doing research isn’t fun, get out of it.” Find something instead that you enjoy working at.

Perseverance also is a characteristic Ryan esteems. For years, when he suspected proteinase inhibitors were defense-related in plants, the other people working on them were focusing on animal systems and the biochemical characteristics of the inhibitors and did not appreciate their potential importance in plants. But Ryan and his research team kept working until nature revealed his suspicions.

Later, a

U.S.
scientist came up with a different mechanism for how an enzyme and its inhibitor come together. For years, his mechanism was accepted and touted at national meetings. Ryan collaborated with Robert Huber of the Max Planck Institute in

Germany
(who later won the Nobel Prize for his structural research on proteins) to help show the mechanism was different. The

U.S.
scientist previously had told Ryan he should quit his work because he was wrong. Of course, he wasn’t, as time and effort bore out.

Perhaps the most severe challenge came from competitors in

England
who convinced many in the discipline that systemin was not the wound signal at all. Instead, they said, it was an electrical signal. Ryan reviewed their paper for the journal Nature and found the methodology faulty. Nonetheless, “they dogged the editor until he published the paper,” Ryan says. The New York Times picked up on the work, then scientists in
Germany and

Nebraska
.

“I walked around battered for a year,” he recalls. “I was getting people in the audience (at professional presentations) really giving me a hard time because I wasn’t buying this electrical phenomenon.

“And we just kept going. The scientists finally refuted that data about three years ago, in one sentence, in an obscure article, and said they don’t believe that anymore.

“You just have to work through those things and not let that kind of nonsense influence you.”

Perseverance has also seen Ryan through the changes that technology fosters, such as the abilities to separate proteins or isolate and identify genes.

“When we first started really studying the system, say in the late 1970s, if somebody had told me that by 1984 we would have the gene for the inhibitors identified and by the late 1980s we’d have it in plants, expressed, I would never have believed that. And now it’s just a piece of cake.”

Ryan promotes cooperation as a necessary quality. In choosing colleagues to join his lab, whether students, post-docs, technicians or visiting scientists, he not only looks for their keen interest in science and research, but also their willingness to get along and work together. Of the dozens who’ve passed through the lab, he still gets together with many at national conventions and keeps in touch with more through Christmas cards.

His students have gone on to faculty positions at universities worldwide and to jobs in industry and agriculture. Three are setting up their own biological centers or institutes, much like Ryan’s IBC.

“A former student who visited recently made the comment about how much fun everyone had working here, and how so many of them have turned out well,” Ryan says with more than a little satisfaction.

He’s also pleased with how well WSU is turning out.

“When I first came here, people wondered ‘Why there?’ Now, they think you’re lucky to be coming here,” Ryan says. To maintain this upswing in reputation, he says WSU must continue to hire good people. “The reputation of a university rides on its faculty.”

Ryan himself considered leaving WSU at least a few times in his career. He took sabbaticals to the
University of
Washington and Harvard in 1980 and 1981, but then returned to

Pullman
. Offers became more insistent after he was named to the National Academy of Sciences.

“They were lucrative,” he admits, “but I’ve never been in this for the money.

“We had a dream of making this (IBC) into a world-class unit,” he continues. “We had something unusual going. Those dreams were coming true. People here were making a name for themselves. We had established an identity that would have been hard to give up.”

The lifestyle and proximity to family would’ve been tough to lose, too.

“Here, my door is always open. I get to do what I love doing; it’s not everywhere you can say that.”

What he loves doing these days is research. After retiring two years ago, Ryan was hired back at 40 percent time, “which is about 90 percent in reality,” he says. His last graduate student,
Alisa Huffaker (shown with him in the accompanying photo), will graduate this spring. He has applied for grant renewal, but the grant would last three to five years, not long enough for the five- or six-year commitment required to take on more graduate students.

The IBC today has 10 faculty members, 150 people in all, and they’re almost entirely supported by grant money.

Colleagues at WSU and elsewhere are building on Ryan’s work. Among other projects, Ryan is collaborating on using the inhibitors as appetite suppressants. Also, the potato inhibitor has been shown to block carcinogenesis (cancerous tumor formation) in human tissue cultures. He’s working with Kemin Industries in

Des Moines,
Iowa
, on that research.

Not entirely coincidentally, Ryan’s former graduate student Christopher Nelson is president of the company. He also is scheduled as the speaker for the commencement ceremony where Ryan will receive his honorary degree.

Also sharing the moment with Ryan will be his wife, Pat, and his children and grandchildren.

“What’s nice more than anything is what this honor does for my family,” Ryan says. “It gives my grandkids a sense that Gramps has been successful. I’m a role model for my family. Nothing like this has happened to my family.

“Receiving this honor was a shock to me. I was really touched.”

As his science no doubt will continue to touch many others — “Better Things for Better Living.”

“You never know when you do research how it will turn out,” Ryan muses. “You discover something that might be useful to mankind and it just drives you all the time. It drives a lot of people.

“I’ve had a fantastic career.”

Also contributing to this article are the WSU News Service and video interview transcripts by Julie Kerssen for the
Museum of
History and Industry in

Seattle
.

Next Story

Recent News

Regents start search process for next WSU president

The Board of Regents will begin the search process for WSU’s 12th president this week. Applications for the Presidential Search Advisory Committee are now available.