Penn’s John Trojanowski, 76, remembered as neuroscience pioneer

Anyone at a scientific lecture attended by the fellow with a familiar, wild mop of hair atop his 6′4 frame could be sure of this much: When the talk was over, he would be the first with a probing question.

“Hi, I’m John Trojanowski from the University of Pennsylvania,” he would begin, though he hardly needed to say who he was.

Dr. Trojanowski, who identified just about every important brain protein key to a number of neurodegenerative diseases, died on Feb. 8 in Philadelphia. He was 76, and until nearly the end of his life he was still writing grants and papers, and overseeing tens of millions of research dollars to better understand the many pathological proteins that he and his wife and scientific partner, Virginia Lee, had identified or studied during their 45 years together.

By all accounts, their shared passions for science and each other led the pair to some of the most significant findings in their field. When they arrived at the University of Pennsylvania in 1980, Dr. Trojanowski told Lee, a biochemist who was also completing an MBA, that they should look for proteins involved in neurodegenerative diseases.

“We can do this,” he told her. “And we can be successful at it.”

He was given the task of opening up a brain bank at Penn, and after doing an autopsy on a person with Alzheimer’s disease decided that they should take this one brain and isolate the stuff in tangles, one of two major pathologies seen in such brains.

They went on to identify different forms of the tau protein, and the two of them championed the importance of tau at a time when the Alzheimer’s field was obsessed with amyloid, the other common pathology.

“Let’s go after Lewy bodies,” he said shortly after the tau discovery. Lewy bodies were part of the pathology of Parkinson’s disease and dementia with Lewy bodies, but their biochemical composition was not known. The team at Penn identified alpha-synuclein as the key player in Lewy bodies. They started making animal models of these diseases. It would be the only route to identifying molecules and testing them on the road to developing treatments.

They continued their search for proteins and identified TAR DNA-binding protein 43 — TDP-43 for short — in brains of people with frontotemporal dementia, language and behavioral diseases that occur in mid-life. Nobody had even linked TDP-43 to a disease.

Then, they saw something very strange. The abnormal protein was also in the brains and spinal cords of patients with amyotrophic lateral sclerosis, or ALS. By then, in 2006, this team had come to believe that many people with neurodegenerative diseases have a mix of pathologies — meaning it will take a mix of medicines to stop or slow these diseases.

The lab also got some of the first federal grant money to open up the Alzheimer’s Disease Research Center, and they began recruiting and training the next generations of scientists. Dr. Trojanowski led the Biomarker Core for the Alzheimer’s Disease Neuroimaging Initiative, a longitudinal study that has changed how patients are diagnosed.

“They helped create the modern world of neuropathology,” said Michael Weiner, a professor of radiology at the University of California-San Francisco. “For many neurologists, dementia was a clinical diagnosis, but pathologists knew it was a disease and they qualified it and defined it. John was a leader in the field.”

“Any one of their accomplishments in identifying the pathologies in these diseases would be a capstone to an individual’s career,” said John Morris, a physician and director of the Knight Alzheimer’s Disease Research Center at Washington University in St. Louis. “John was never limited to a focus in Alzheimer’s. He understood the complexity and breadth of these neurodegenerative lesions. What a life they have had.”

John Trojanowski was the son of a career Army officer who took his family to live in 10 different places — including two years in Guam — by the time John left home at 18. He was the second of seven children and rather than joining his father’s post-war real estate business in Connecticut, he majored in German at Kings College in Wilkes-Barre on a full scholarship. He got into an MD/PhD program at Tufts University School of Medicine, and studied and worked in Rotterdam for a few years.

His mentor at Tufts, Stan Jacobson, was giving a lecture one day in 1974, and Dr. Trojanowski was passing time reading the notice board when Lee, a Harvard post-doc, spotted him standing nearby .

“I thought he was so handsome,” Virginia Lee would later say. But two more years would pass until she was standing at a bar drinking a Coke when that same guy walked in, and she got up the nerve to make the first move, asking, “Haven’t I met you somewhere before?”

In 1979, Lee was offered a job at a Philadelphia pharmaceutical company and he followed, getting a job at Penn. They married several years later, and he convinced her to work with him, sparking careers that made them standouts in their fields.

The last several years were not easy for Dr. Trojanowski, according to his wife. He slept a lot, and he had several minor falls inside their house, his wife said. He would get up and brush himself off. But in mid-December, a day before his birthday, he had another fall. He climbed up the stairs, sat down on their bed and turned to her. “I think I need to go to the hospital,” he said.

An MRI put the last few years into focus. There were a number of hematomas along his spine. He was rushed into surgery. Twice. A pulmonary embolism and constant infections made recovery difficult. The spinal cord injuries left most of his body paralyzed, and he required a ventilator.

Always both practical and passionate, the couple held a Zoom call and hosted hundreds of colleagues, friends and family from all corners of the globe. She propped him up on his hospital bed, and she put on his glasses so he could watch the computer screen. The hour was raw, reflective, and, most of all, loving. His doctors thought he had a chance of recovery, but the infections persisted, and antibiotics were not working. He is survived by Lee and five of his brothers and sisters.

Daniel Skovronsky trained with the couple before going on to a distinguished career in drug development. In November, he stopped by the lab for a visit. He had noticed the changes in Dr. Trojanowski, and was struck by the poignancy of his gentle parting words: “Make sure you tell people you trained with John and Virginia.”

Jamie Talan is a science writer who spent her career covering the brain. She is co-author of “The Death of Innocents,” which won an Edgar Award for best nonfiction in 1998, and “Deep Brain Stimulation.” She is an assistant professor of science education at the Zucker School of Medicine at Hofstra/Northwell.