The Tiny Molecules Helping Surgeons See Cancer and Opening New Paths for Treating Disease
An interview with Prof. Bilha Fischer, a medicinal chemistry researcher at the Dangoor Center for Personalized Medicine and in the Department of Chemistry at Bar-Ilan University, about the fascinating journey from a small molecule to the possibility of a major health breakthrough
An oncology surgeon faces a complex challenge: an ovarian tumor hiding beneath fat cells. “How far should you cut? Too much, and you damage healthy tissue; too little, and the cancer keeps spreading,” explains Prof. Bilha Fischer from the Department of Chemistry at Bar-Ilan University.
The solution developed by Prof. Fischer, together with Prof. Yaron Shav-Tal, Bar-Ilan’s Vice President for Research and head of the Dangoor Center, is elegant in its simplicity: dyes that are sprayed onto tissues during surgery. “Within 30 seconds, the dyes penetrate the cells,” she explains. “They selectively stain cancerous cells more than healthy ones, allowing the surgeon to see the tumor and its size even if it is hiding beneath fat cells, because our dye doesn’t stain fat cells.”
This technology, called FGS – Fluorescent Guided Surgery, is part of a growing trend in the medical world: giving surgeons tools to see the tumor and its boundaries. “It’s very critical to give them real-time tools, so they know exactly how far they’re supposed to cut during the operation.”
The advantage of the dyes developed by Fischer and her students lies in their availability. “Other dyes need to be injected into the patient a day beforehand, and that’s a whole operation; here, it happens on the fly during surgery.” In addition, the dyes are non-toxic and their synthesis is simple. According to Prof. Fischer, they developed a “supermarket of dyes,” a range that allows matching each dye to the specific need. “We have dyes that emit in visible light, and we also have dyes that emit at wavelengths in the near-infrared region, which makes it possible to detect deeper into the tissue.”
When personal stories drive big science in degenerative diseases
Developing dyes for imaging cancerous tumors is only one of the projects Prof. Fischer leads. As a medicinal chemist by training, she works on developing drugs for diseases that mainly affect older adults, like Alzheimer’s, glaucoma, and osteoarthritis. “Aging brings not only experience and wisdom, but also many weaknesses of the body and its systems.”
In the case of Alzheimer’s disease, the motivation was especially personal. “It was a family matter; my grandmother had this disease, and so did my mother, so I had a very strong drive to look for drugs that would slow the progression of Alzheimer’s.” There was also a personal motivation behind the cancer-dye project: “It began with the passing of a beloved friend of mine who had breast cancer that spread to the ovary.”
“In all the diseases we’ve studied, you can’t turn back the clock, but the name of the game is slowing the rate of deterioration or sometimes even preventing it,” Prof. Fischer explains. “So with another disease we worked on, osteoarthritis, which causes the cartilage to erode, we tried to prevent the deterioration, maybe even to halt the erosion.”
Multi-target drugs: the magic of science
What does it feel like when a small molecule you synthesized in the lab proves that it can treat a disease?
“Wow, it’s something that to this day I’m not sure I fully grasp,” Prof. Fischer admits. “Because I know just how endlessly complicated biological systems are, I’m honestly amazed that a small, simple molecule can set off a whole cascade of biochemical events that eventually show up on the macro level, in the way it affects a patient’s health.”
Prof. Fischer gives concrete examples: “For example, slowing Alzheimer’s disease, as we saw in transgenic mice (genetically engineered mice into whose genome an aggressive model of the disease was artificially introduced), or in glaucoma, where we manage to dramatically reduce the intraocular pressure in rabbits or rats.” She adds, “The same is true for samples of knee cartilage from patients undergoing surgery; we show that it’s really possible to stop the deposition of a mineral that’s simply destructive to the cartilage, using our compounds,” Prof. Fischer says with a satisfied smile.
And immediately she lights up again: “Even for me, someone who knows these systems, it’s hard to believe. It’s a miracle, really, like magic. How can I, and of course my students, make such dramatic changes in an organism and actually improve its health? It feels like a wonder to me. Even now, after all these years.”
One of the central principles in Prof. Fischer’s work is developing multi-target drugs, a single molecule that can address several targets. “Compounds we developed to slow the progression of Alzheimer’s, for example, can act on several targets at once.”
How does it work? “Through one mechanism of the drug’s action, it binds to a specific receptor and protects nerve cells in the brain, giving what we call neuroprotection. A second mechanism is that the drug can also bind metal ions like copper and iron, which are involved in generating oxidative radicals that are destructive and toxic to the brain and to nerve cells, and by binding them, it neutralizes their activity. We also showed that they reduce the deposition of a toxic protein, which slows the progression of the disease.”
The receptor is activated by the drug and causes the spongy tissue in the front part of the eyeball to contract.
Breakthrough in glaucoma treatment: squeezing the eye’s spongy tissue
One of Prof. Fischer’s major breakthroughs is developing a drug for glaucoma, a disease in which high pressure in the eye damages the optic nerve and can lead to blindness. “First of all, the drop in pressure with the compound we developed is significant. It can reach up to 40 percent, which is a lot, and that makes it better than the compounds currently on the market.”
The process began with understanding the biological mechanism. “We chose to activate a specific receptor that we already knew existed in the eye, inside the tissue responsible for draining excess fluid out of the eye. We looked for an agonist, a compound that would selectively activate that receptor.”
How does it work in practice? Prof. Fischer uses a simple metaphor: “It activates the receptor, which causes the tissue to be squeezed. You can think of it like a sponge full of water; when you compress it, the water comes out. In the eye, there’s a spongy tissue in the front part of the eyeball. When the receptor is activated by the drug, it makes that tissue contract, squeezing the fluid out.” This development is also already in advanced stages. “It worked successfully in rabbits and rats,” Prof. Fischer notes.
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Photo credit: Yoni Reif
“Nucleotides weren’t previously considered potential drug compounds. We showed that these substances definitely have therapeutic potential.”
Reaching the patient: collaboration, commercialization, and personalization
What is unique about Fischer’s scientific approach? “Most of the compounds we’ve worked on in the context of developing drugs for various health disorders share a common denominator, and that common denominator is that they’re synthetic derivatives of nucleotides that we synthesized.” Nucleotides are the building blocks of nucleic acids. These are small, essential molecules with two main roles: storing and using genetic information, and supplying energy to the cell.
Prof. Fischer’s major innovation was demonstrating that nucleotides can serve as a starting point for drug development. “Nucleotides weren’t previously considered potential drug candidates for various reasons. For example, they’re highly soluble in water, so they don’t cross cell membranes. In addition, these compounds may cause side effects because they can bind to different proteins,” she explains, before describing the novelty: “We showed, in a way that still feels like a miracle to me, that these compounds definitely have therapeutic potential, and we tested them on different models of different diseases and on various animal strains. We found creative solutions; in glaucoma, for example, the administration is local, meaning you drip the compound directly into the eye, so there’s no problem of solubility, no problem of penetration, and you don’t have to swallow it orally.”
Have any of these developments actually reached patients yet?
“The problem is always commercialization,” Prof. Fischer explains honestly. “Big pharmaceutical companies are willing to pay huge sums, but only for drugs that are already in the main, final stage of clinical trials in humans. That’s what’s required before a drug company can ask health authorities for marketing approval. Because the failure rate in drug development is enormous, they prefer to play it safe and pay huge amounts for drug candidates that are already in the last stage of development.”
The scientific work, development, and, of course, implementation do not end with the miracle discovery that happens in the lab. Collaborations are essential to Prof. Fischer’s work. “We’ve had, and still have, collaborations with academia, hospitals, and industry. It’s very important because it allows us to expand the research.” She especially highlights “the collaboration with Prof. Yaron Shav-Tal, Bar-Ilan’s Vice President for Research, on developing the diagnostic dyes that help oncology surgeons.”
Prof. Fischer gives an example of a personalized-medicine initiative led by the Dangoor Center: developing tools that enable more precise diagnosis and more targeted treatment. “One of our projects is identifying cancer biomarkers using fluorescent methods so we can determine which subtype of cancer a specific patient has. For example, a subtype of breast cancer is really an entire umbrella of diseases. So we developed a method that makes it possible to identify the specific breast-cancer subtype that the patient has.”
“I didn’t think I’d go into research. As someone who loves calligraphy, furniture restoration, writing, and drawing, both the artistic side and the scientific side are important to me.”
“I wanted to pass on my love for wildflowers.” Book cover.Photo: Courtesy of the interviewee
Creativity in science and art: a children’s book about wildflowers
Beyond her research work in the lab, Prof. Fischer is also a writer and illustrator. She wrote and illustrated the children’s book Agi and Horti’s Travel Journal to the Wildflowers of Israel. “I really love wildflowers, and I went on countless trips to see rare wildflowers, even in far-off places. I wanted to pass that love on,” she shares. “I wanted to write a children’s book and dedicate it to my grandchildren, who at the time I didn’t yet have. Now, thank God, I have five grandchildren, and by the time I wrote and illustrated the book, they were already born, and their names appear in it,” Fischer smiles.
“Nature has always been a source of inspiration for me, both for art and for science. I think both require creativity. Science is definitely something very, very creative. For me, it’s a hobby no less than illustration.”
When she’s asked what the young Bilha would think of Prof. Bilha the researcher, she laughs: “I think she wouldn’t believe it. I didn’t think I’d go into research. Not at all. As someone who loves calligraphy, furniture restoration, writing, and drawing, both the artistic side and the scientific side are important to me. In the end, the scientific side won. It wasn’t an easy decision.”
I asked Prof. Fischer to choose the project closest to her heart. She hesitated: “They were all my children. I don’t know. I’m proud of all of these projects. Each one is wonderful to me. There isn’t something specific; each one is something astonishing and moving. The fact that a tiny molecule can do such work, it’s like a butterfly flapping its wings in Alaska causing a volcanic eruption in the Philippines. Something just like that. Here too, the butterfly’s wings are that tiny molecule that triggers some kind of effect that heals or helps patients. So to me, it’s incredible, truly the butterfly effect.”
Last Updated Date : 29/12/2025
