Theodor Diener, who discovered the smallest infectious agents, dies at the age of 102

Finding something infinitely small is never easy. But it is much more difficult if the seeker does not know what to look for.

Theodor Diener, a plant pathologist with the Federal Agricultural Research Service, faced that problem when he began researching spindle tuber disease, a condition that makes potatoes scrawny and misshapen.

Dr. Diener, who was 102 when he died March 28 at his home in Beltsville, Md., worked for years to find the culprit, resulting in the discovery of the smallest known infectious agent, which he called a viroid.

Spindle tuber disease, first identified in the 1920s, can sometimes have disastrous consequences for crops. Studies show that the condition can lower potato crop yields by up to 64 percent; only strict quarantine and in some cases destruction of entire crops can contain this highly contagious disease. But even decades after the disease was diagnosed, scientists still weren’t sure what caused it.

Dr. Diener and colleagues like William B. Raymer of the Research Service, part of the Department of Agriculture, spent most of the 1960s trying to solve the puzzle.

They studied the pathogen in tomato plants, which they found had a much shorter incubation period for tuber rot disease than potatoes, and used advanced techniques to find out that this infectious agent contained no proteins and that RNA, or ribonucleic acid, is one of the building blocks of life was crucial.

Dr. Raymer left the research service for a job in private industry in 1966, and Dr. Diener “spent the next five years isolating and characterizing the viroid, verifying his experiments, filling in the gaps” and “preparing to meet the skepticism that generally greets proposals of new ones,” impossible’ concepts,” according to a 1989 article in the journal Agricultural Research titled “Tracking the elusive Viroid.”

At the time, scientists thought something as small as viroids, which are one-eightieth the size of many viruses, were too miniscule to cause infection.

Like viruses, viroids reproduce by invading healthy cells and reprogramming them to duplicate the genetic makeup of the viroid rather than that of the cell.

But viruses, which can be made of DNA or RNA, have a protective coat made of proteins and code for proteins once they’ve entered cells. Viroids, on the other hand, are made only of RNA, do not have the protein coat, and do not code for proteins.

“The method of causing disease is fundamentally different from that of all other viruses,” said Dr. Diener at an international meeting of virologists in 1972.

After identifying the viroid that caused spindle tuber disease, he helped develop a test to detect it. He was subsequently awarded the National Medal of Science by President Ronald Reagan at a Rose Garden ceremony at the White House in 1987.

William Haseltine, a virologist and former professor at Harvard Medical School who has a series by Article about viroids for Forbes magazine this year, said in a telephone interview that Dr. Diener “discovered an entirely new branch of life, probably the most fundamental branch of life, at least by my definition.”

The discovery of Dr. Diener has implications for the scientific understanding of the origin of life and for medicine, contributing to breakthroughs such as the use of messenger RNA to develop vaccines for Covid-19, said Dr. Haseltine.

Since the discovery of Dr. Diener, scientists have identified more than 30 different viroids that cause diseases in plants, such as the avocado sunblotch, coconut cadang-cadang, pear bladder cancer and hop latent viroids, which can be devastating to hemp and cannabis crops.

Theodor Otto Diener was born on February 28, 1921 in Zurich, the only child of Theodor and Hedwig (Baumann) Diener. His father was a postman, his mother an accountant.

As a child he was fascinated by animals and kept a colony of mice, a turtle and a canary, much to the dismay of his parents. His father, he wrote in a self-published memoir, “Of Humans, Humanoids, and Viroids” (2014), did not appreciate his consuming interest in “little living creatures.”

He “often shook his head in disbelief when I was narrating enthusiastically—describing properties of a small insect, worm, or fungus,” wrote Dr. Diener.

Dr. Diener did aircraft maintenance for the Swiss Air Force during World War II and in 1948 he completed his doctorate in biology at the Swiss Federal Institute of Technology.

He emigrated to the United States in 1949 and, after a short time in New York City, moved to Spokane, Washington, for a position at Washington State College (now Washington State University). About ten years after coming to Washington, he moved to Maryland to work in the government research department.

Dr. Diener’s first marriage, to Shirley Baumann, ended in divorce. In 1968 he married Sybil Fox, who died in 2012.

He is survived by three sons from his first marriage, Michael, who confirmed death, Theodore and Robert; five grandchildren; and three great-grandchildren.

Other awards from Dr. Diener include his election as a member of the National Academy of Sciences and to the American Academy of Arts and Sciences. In 1987 he received the Wolf price in agriculturea $100,000 prize awarded by the Wolf Foundation in Israel.

Viroids can be much more than agricultural pests. Research suggests they existed in the earliest stages of life on Earth, unnoticed until Dr. Diener’s search began.

Dr. David A. Relman, a microbiologist at Stanford University, wrote in an email about Dr. Diener: “His discovery of viroids and their role in plant diseases helped to reveal the role of RNA molecules in fundamental biological processes, and possibly in the origin of life itself.”

Ashley Shannon Wu contributed reporting.