The space in between

Decades ago, when a journal editor removed the term ‘nano’ from an article he had submitted, pioneering researcher Raoul Kopelman (1933-2023) was at a loss for words. The prefix, which is Greek for ‘dwarf,’ stands for one-billionth of a meter — or 10^-9 — in the International System of Units. It was an accurate descriptor for the teeny, tiny particles at the heart of Kopelman’s study, but the editors feared readers wouldn’t know the term. They opted for ‘sub-micro’ instead.

Kopelman, who joined the U-M chemistry faculty in 1966, was less concerned with the label than the realm it described. Mostly, it was the space between those atoms, molecules, and clusters that really intrigued the scholar.

“Whole universes are in there,” he told Michigan Today just months before he died in 2023.

Let’s get small

Kopelman and mentee Panos Argyrakis pose with a Kopelman Research Poster at the Chemistry Building, 2023. (Image courtesy of Shirli Kopelman.)

Some 57 years after he arrived at Michigan, Kopelman remained an active participant in ‘NanoWorld,’ advancing breakthroughs in precision medicine and developing interdisciplinary graduate-level courses in chemistry, technology, climate science, and artificial intelligence.

Research topics ranged from solid-state physics to biomedical engineering. All of his work was characterized by a rare focus on interdisciplinarity and most of it featured collaborations with treasured mentees who continue to have an impact in the industry; many are tenured professors at prestigious universities around the world.

Kopelman authored more than 700 scientific papers, patents, and books, and is perhaps best known for developing the Hoshen-Kopelman algorithm, a simple and efficient algorithm for labeling clusters on a grid, where the grid is a regular network of cells, with the cells being either occupied or unoccupied. The algorithm’s practical application is so widespread in modern technology that scholarly citations of the work pop up every single day on Google Alerts. Some 5,000 citations have appeared since publication of his 1976 paper “Percolation and Cluster Distribution. I. Cluster Multiple Labeling Technique and Critical Concentration Algorithm.”

The mentor’s journey

Argryakis leaves Kopelman’s office for the last time. A regular visitor to Ann Arbor since 1980, Argryakis often arrived at his co-author’s office with a vexing challenge to solve. (Image courtesy of Shirli Kopelman.)

In his final months, Kopelman was eagerly preparing for a reunion, on what would have been his 90th birthday, with more than 70 doctoral students and dozens of postdocs who had been trained in his U-M lab. Before arriving in Michigan in 1966, he was at the Technion (the Israel Institute of Technology), Columbia University, Harvard University, and Caltech. Four of his former students are Nobel laureates: Richard Smalley, Eric Betzig, Roald Hoffman, and Arieh Warshel.

One of his closest colleagues and former students, Panos Argyrakis, PhD ’79, had been visiting his mentor and longtime co-author twice a year since 1980. Argyrakis is a professor of computational physics at Greece’s University of Thessaloniki. It was Kopelman who set Argyrakis on that path five decades ago as together they discovered the nascent technology of computer modeling.

Converting data from analog to digital in the early days (using a computer that consumed the entire floor of a university building) offered a scientifically robust method to analyze, corroborate, and advance Kopelman’s research. He was working with lasers in the ’70s and when Argyrakis demonstrated an aptitude for computational modeling, Kopelman seized upon his mentee’s skills.

“He realized early on that I was better at calculations than doing measurements in his lab,” Argyrakis says. “I was able to study the same systems as Raoul, but computationally, rather than from the lab bench.”

A glass half full

In October 2023, Michigan Ross professor and Raoul’s daughter, Shirli Kopelman, curated and hosted a memorial symposium to celebrate her father. Stellar Multidisciplinary Research hosted more than 100 of Kopelman’s mentees and colleagues; they spent the day reflecting on the scholar’s research impact, which transcended academic disciplines, inspired entrepreneurial and institutional innovation, and contributed to the public good.

“Raoul was competitive but collegial, a ‘glass-half-full’ guy,” said Betzig, co-recipient of the 2014 Nobel Prize in Chemistry. “Today’s medical molecular cancer research is an extension of Raoul’s original idea.”

Betzig is a professor of molecular and cell biology, the Eugene D. Commins Presidential Chair in Experimental Physics, a Senior Fellow at the Janelia Research Campus, and Investigator of the Howard Hughes Medical Institute at the University of California, Berkeley. His mentor inspired an ability to move between fields as he made publishable, important contributions in multiple areas.

“Raoul had an immense imagination and sought impact in everything he did,” Betzig said.

That imagination allowed Kopelman to reinvent himself as he investigated new areas, said Theodore Goodson III, the Richard Bernstein Collegiate Professor of Chemistry at U-M.

“No matter what we were going to talk about — the theory of excitons or some applications about biomedicine — I knew that when I walked out of the room a couple of hours later, we would have some kind of solution to the problem,” Goodson said.

Mad skills

Argryakis would arrive at Kopelman’s office with data recorded from his computer in Greece. The label on this early version of a flash drive reads “ZEUS1.” (Image courtesy of Shirli Kopelman.)

Argyrakis, a scholar of theoretical condensed matter physics, remembers using his prehistoric computer in Greece in the early ‘80s. At the time it was considered cutting edge and small, considering the early ’60s version took up an entire room. Before trekking to Ann Arbor, Argyrakis would transfer his data onto a hard floppy disc the size of a vinyl record album that “weighed about 10 pounds.” Much of his work with Kopelman revolved around particle systems and diffusion, dubbed the “random walk.” The phenomenon exists throughout nature, from single atoms to entire galaxies. The duo co-authored numerous papers on the topic as Kopelman successfully attracted funding to continue.

“Raoul was among the top faculty for bringing money to the chemistry department, which at times was very difficult,” Argyrakis said. “One of his biggest satisfactions was to pursue groundbreaking, high-impact research and at the same time, guide his students to become independent thinkers.”

Kopelman’s determination could not be contained, even as heart issues and other medical conditions temporarily affected his movement and eyesight. U-M’s Xueding Wang, the Jonathan Rubin Collegiate Professor of Biomedical Engineering, was co-writing a proposal with his colleague when he suggested they defer until Kopelman was in better health.

“Raoul said, ‘Why? I still have one hand that can type. I still have one eye that can look at the screen.’ So we worked on it together — and we got funded,” Wang said.

A reception in Kopelman’s honor, October 2023. (Image courtesy of Shirli Kopelman.)

Kopelman’s energy wasn’t all about academics, though. He placed an equal emphasis on social discovery. He was known to invite students to live with his family as needed and opened his door for dinners and other casual interactions.

“He treated everyone like a big family and you got to see how scientists really worked, what they really thought,” said Eric Monberg, PhD ’77, of Optical Fiber Research.

“Raoul was a model mensch,” said Rachel Goldman, Maria Goeppert Mayer Collegiate Professor, U-M professor of materials science and engineering, professor of physics, and associate director of the Program in Applied Physics. She had planned to invite the scientist to join the department’s advisory board before she learned he had passed away.

In an editorial published in ACS Sensors, “Remembering Raoul Kopelman (1933–2023),” Heather Clark, PhD ‘99, described her mentor’s unique approach to science and his genuine kindness as a person.

A mentor’s legacy

Argryakis and Kopelman met in the late ’70s when Argryakis was pursuing his PhD. They remained friends and collaborators for life. (Image courtesy of Shirli Kopelman.)

It’s mind-boggling to consider the dramatic progress in the field of computing since Kopelman first recognized its potential. In the 1960s, he advocated the use of computing in the chemistry department, despite detractors who dubbed the effort “anti-educational.” Even so, he introduced the use of computer punch cards in his undergraduate lab course in physical chemistry. In 1977, while serving on the Rackham Graduate School Executive Board, he proposed that PhD students write and print their theses using the university computer. The faculty were dubious.

Argyrakis, though, was up to the challenge. He’d spent so much time in the university’s computer lab on Kopelman’s behalf that he’d befriended the author of a rudimentary, experimental, and text-only word-processing program. To locate the cursor, the user twirled knobs to control a vertical and horizontal hairline until they intersected, because the mouse had not been invented yet. Printing a huge document that complied with the university’s stringent doctoral standards wasn’t easy, but in 1978, Argyrakis became the first doctoral candidate at Michigan to write and print his entire thesis using a computer.

At the symposium in 2023, Argyrakis had tears in his eyes when he spoke: “Raoul was an integral part of my life for 50 years minus three months. He was always there to encourage, to offer his empathy at difficult times, and help to elevate one’s spirits. With his acumen, he offered himself and all his resources to that purpose.”

Fantastic

From 2003-23, there were two “Professor Kopelmans” at the University of Michigan: Chemistry’s Raoul Kopelman and Michigan Ross professor Shirli Kopelman. Father and daughter were good friends and close colleagues. (Image courtesy of Shirli Kopelman.)

In his final years, Kopelman focused on precision medicine, covering novel diagnostic and therapeutic techniques for cancer and heart disease. Implanting nanoparticles that precisely and specifically target and kill dangerous cells, the technology uses noninvasive and otherwise harmless red light, instead of high-energy lasers, X-rays, or gamma rays. With collaborators in U-M’s Medical School, Kopelman applied this technology to treat cancer and heart arrhythmia in rodents and sheep.

He may have been captivated by the nano, but Kopelman always favored the big picture. He preferred to focus on the future instead of the past — unless he was reflecting on his early childhood in Israel. His family had fled Vienna during World War II to escape the Nazis. They settled in Tel Aviv when Kopelman was five years old.

“I would stare at the night sky and could see galaxies beyond the Milky Way,” he said.

When he read Jules Verne’s Twenty Thousand Leagues Under the Sea as a child, and later, The Fantastic Voyage by Isaac Asimov, Kopelman set his sights on the undiscovered and as-yet-unnamed world of nano. Asimov’s plot tracks a research crew reduced to a microscopic fraction of their original size, boarding a miniaturized atomic submarine and being injected into a dying man’s carotid artery.

Metaphors like that tiny submarine inspired Kopelman throughout his career, said daughter Shirli Kopelman.

“He saw fractals where others saw trees,” she said. “His work will continue to light the path of future generations.”

(Lead image courtesy of Shirli Kopelman: Raoul Kopelman and his mentee/colleague Panos Argyrakis, PhD ’79, met twice a year for decades, continuing to collaborate until Kopelman’s death in 2023.)