By Dirk Hoffman
Published January 2, 2024
Frederick Sachs, PhD, a world-renowned biophysicist and a SUNY Distinguished Professor of physiology and biophysics at the Jacobs School of Medicine and Biomedical Sciences at the University at Buffalo, died Dec. 27 at the age of 82.
He began his illustrious career at UB in 1975.
A major portion of his career was spent investigating how cells sense physical forces, like touch, at the molecular level. His research interests centered around mechanical and electrical biophysics — from molecules to organs — and the development of scientific tools, such as the creation of an ultra-fast pressure stimulator, and a sensor chip to measure cell volume in real time.
His greatest lifetime achievement – and one that will undoubtedly stand the test of time — is his profound contributions to the field of biomedical research called mechanical transduction.
In 1983, Sachs made his seminal discovery, identifying and characterizing the first mechanosensitive ion channels. Found in every cell of the body, these sensors form the basis of our senses of hearing, touch, balance and tissue volume.
His laboratory rapidly became a center for work on mechanosensitive ion channels and researchers from around the world visited to learn techniques used to study these channels in different cells.
In addition to understanding the basic science of cell properties, Sachs explored how biomechanics is involved in disease progression and the discovery of drugs to intervene.
He led research that resulted in the identification of a peptide found in Chilean rose tarantula venom that suppresses mechanical senses in cells. This discovery entered preclinical testing as a treatment for individuals with Duchenne muscular dystrophy whose muscles have dysregulated mechanical responses.
Beyond spider venom, Sachs also conducted the first voltage clamp studies of isolated adult heart cells. He was also responsible for the first single-channel recording from tissue cultured cells.
Sachs developed novel biophysical concepts through the innovative use of quantitative electrophysiology, bright field, fluorescence, internal reflection, atomic force and electron microscopy, auditory biophysics, mathematical modeling, programming, instrument and software design, and silicon microfabrication.
After developing the tools to characterize the mechanosensitive ion channels, he discovered through natural products screening that a component of tarantula venom could act as a pharmacological agent to specifically block these channels. To date, it is the only biological substance known to possess this property.
He solved the molecular structure of the venom peptide and synthesized it. This work opened an important new area of drug development.
To help develop the peptide as a drug, he co-founded in 2009 the UB spinoff firm Tonus Therapeutics with two colleagues in his department — Thomas M. Suchyna, PhD, research associate professor, and the late Philip Gottlieb, PhD, research associate professor — along with Jeff Harvey, a local stockbroker whose grandson had Duchenne muscular dystrophy.
That tarantula peptide, called GsMTx-4, was modified and chemically synthesized in the laboratory, and is being tested as a potential therapy designed to slow the muscle deterioration that characterizes muscular dystrophy.
The U.S. Food and Drug Administration designated GsMTx4 as an orphan drug for Duchenne muscular dystrophy, a designation recognizing promising methods of treating rare diseases with the potential to fast-track its approval.
Suchyna began working with Sachs in 1997 at the start of his career and said, “at that point Fred was the ‘king of mechanosensitive channel research,’ so I was stepping into a lab that was at the forefront of a burgeoning research field, which was a huge step in my career.”
“Fred was incredible at thinking outside the box, always asking us to try a different, and usually unorthodox approach,” Suchyna said. “He would come up with the most incredible experiments that other investigators would consider too difficult. And for the school itself, his publications brought so much notoriety to our department,” he added.
“When we discovered the peptide, it turned into a tremendous amount of research — from studying its novel mechanism of action, to drug development, and the creation of analogs with new functions,” Suchyna said.
“At this point, we are still developing GsMTx4 further. We are actively modifying the peptide, looking at ways to make it a biomarker for tissues under mechanical stress, and also trying to target the peptide to specific tissues to reduce off-target effects and increase its attractiveness to pharmaceutical companies. Fred was actively advising me on these projects up to last week.”
The clinical implications of Sachs’ findings were applied in studies including atrial fibrillation, stress-induced Ca2+ uptake in dystrophic muscle, volume regulation in red blood cells of individuals with various forms of anemia, and stress-induced endothelin production in glial brain cells.
Sachs also developed an advanced software package called QuB that investigators use for analyzing single channel data.
Sachs was awarded the 2013 Kenneth S. Cole Award from the Biophysical Society. He received the award — given to only one investigator annually — for his significant contributions to the understanding of cell membrane biophysics.
Arnd Pralle, PhD, professor of physics in UB’s College of Arts and Sciences, first met Sachs when he was a graduate student in the European Molecular Biology Laboratory.
“Fred had a deep love for understanding how cells function within the realm of physics. His enthusiasm was contagious,” he said. “Fred shared his insight into biophysics freely and captivatingly. There wasn’t a seminar which Fred attended where he didn’t pose a curious insightful question or gave an encouraging remark at the end.”
Pralle noted Sachs was an active part of the Biophysical Society where he served on the council and the governing body, for each decade of his long scientific career.
He received an Entrepreneurial Spirit Award at UB’s annual Inventors and Entrepreneurs Reception in 2015 and was awarded numerous patents through his research at UB.
He was nominated for the Nobel Prize in Physics in 2011 by Alexander G. Petrov, PhD, a professor of physics and a fellow of the Bulgarian Academy of Sciences.
Recognized for his exceptional contributions, Sachs received several other prestigious awards, including the SUNY Chancellor’s Research Recognition Award (2003), SUNY Distinguished Inventor (2002), UB Distinguished Professor (2002), UB MiniMed Lecture (2002), Stockton Kimball Award (2001), NSF Nanotechnology Review Panel (2001) and a Fogarty Fellowship (1992).
In addition to his numerous accomplishments, Sachs was recognized by the 1987 Guinness Book of World Records as the inventor of the world's smallest thermometer, the ultra micro-thermometer. This device, about one-fifth of the thickness of a human hair, played a pivotal role in measuring the temperature of single cells.
Sachs was a postdoctoral fellow in biochemistry and biophysics at the University of Hawaii, taught organic chemistry at Chaminade College and served as a staff fellow at the National Institutes of Health before beginning his career at UB.
He earned his doctoral degree in physiology from the SUNY Upstate Medical Center after earning a Bachelor of Arts degree in physics from the University of Rochester.
Outside the lab, Sachs spent considerable time on artistic pursuits.
He was an avid banjo player and played a large repertoire of folk songs, getting together weekly to jam with other musician friends.
Sachs also used kayaking as a form of meditation, and enjoyed the rhythm of just floating out on the waves of the Niagara River.
Growing up on a farm in Putnam County, he learned to weld as a young man. Decades later, he returned to welded steel sculpture as an art form, using principles of physics to explore motion, wind and balance.
For Sachs, steel sculpture represented a totally different mindset from doing research in his lab.
“It is possible to represent emotions, such as happiness, sadness, amusement and even something a bit more complex, such as disappointment. It doesn’t take much steel to do it, but it does take imagination and a bit of patience, which I enjoy,” Sachs said in a 2016 interview about his art.
“The return is so immediate compared to writing grants. That, really, is my reward, especially when the piece turns out the way I wanted it to,” he said. “When you can walk away and come back and look at it and like what you’ve done, that is all the applause I need.”
He is survived by his wife, Jane Jacobson; and his four children, Shana Pergande, Janna Willoughby-Lohr, Benjamin Sachs and Bobbie Sachs; four grandchildren; and two brothers, Jon and Dan Sachs. His son, Chris, predeceased him in 2008.