ISRAEL AT WAR - DAY 145

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Israel at 75: InterviewSchwartz is only the 4th woman to receive award for science

For scientist Michal Schwartz, Israel Prize is rewarding milestone in ongoing journey

Weizmann Institute neuroimmunologist bucked convention to prove that brain is not isolated from immune system, leading to possible therapies to treat Alzheimer’s and other diseases

Renee Ghert-Zand is the health reporter and a feature writer for The Times of Israel.

Israel Prize recipient Prof. Michal Schwartz (Courtesy of Weizmann Institute of Science)
Israel Prize recipient Prof. Michal Schwartz (Courtesy of Weizmann Institute of Science)

Internationally renowned Weizmann Institute of Science professor of neuroimmunology Michal Schwartz will receive the Israel Prize for life sciences on Wednesday, Israel’s 75th Independence Day.

A trailblazer in her field, Schwartz is being recognized for her discovery of the connection between the brain and the immune system, which has led to possibilities for harnessing the body’s immune system to treat neurodegenerative brain diseases such as Alzheimer’s and dementia.

Schwartz is only the fourth woman to receive an Israel Prize for science since the prize’s inception in 1953. The Israel Prize is the country’s highest award.

More than 20 years ago, Schwartz began to challenge the medical and scientific dogma that the brain was self-contained. For many decades, it was believed that the brain was separate from the immune system because of the blood-brain barrier and that any immune activity in the brain was a sign of pathology.

“It didn’t make sense to me that an organ that is so precious, that cannot be replaced or transplanted, would give up its evolutionary potential of being assisted by the immune system,” Schwartz told The Times of Israel in a recent interview at her office at the Weizmann Institute in Rehovot.

Her office is a testament to her ultimate success in proving to the scientific community that the brain is not immune-privileged. One wall is completely covered in framed covers of journals in which her articles and studies have been published. The other walls and shelf space are filled with Israeli and international awards and certificates of recognition.

“We published our first papers challenging this dogma in 1998-1999. They were met with a lot of skepticism,” Schwartz said.

“But I decided to keep going. I decided it was my responsibility to continue to dig into the mechanism and to support our observation with more data,” she said.

Prof. Michal Schwartz stands in front of wall adorned with covers of journal in which her work has been published at her office at the Weizmann Institute of Science in Rehovot, Israel, April 20, 2023. (Renee Ghert-Zand/Times of Israel)

The major turning point came when Schwartz and her team demonstrated that young animals with healthy brains, but defective immune systems, suffer from a reduction in cognition and the ability to cope with mental stress.

Schwartz’s student Jonathan Kipnis (now at Washington University in St. Louis) showed that even social behavior is impaired if the brain is young and healthy but the immune system is compromised.

“When we restored the immune system by bone marrow transplantation, we restored cognition and other functions of the brain,” Schwartz said.

Schwartz and Kipnis discovered that the immune cells that help the brain reside at its borders, including the brain-meninges barrier and the cerebral spinal fluid (CSF)-brain barrier. These immune cells help the brain from afar, but if the brain needs them for its repair, it will control when and how to use them.

Schwartz has coined the term “brain-immune ecosystem” to describe how the brain and the immune cells on its borders interact with one another.

This illustration made available by the National Institute on Aging/National Institutes of Health depicts cells in an Alzheimer’s affected brain, with abnormal levels of the beta-amyloid protein clumping together to form plaques, brown, that collect between neurons and disrupt cell function. (National Institute on Aging, NIH via AP)

The possibility of treating Alzheimer’s disease and dementia came into the picture when it was discovered that communication between the brain and the nearby immune cells is impaired with aging.

“We concluded that cognitive decay or reduction that happens with aging is not necessarily a reflection of chronological aging, but rather of the aging of the immune system,” Schwartz said.

“If the immune system is aging, it will affect the brain. It’s not the primary cause of disease, but it can be a trigger for the timing, severity, and speed of progression of the disease,” she explained

Based on a deep understanding of the cross-talk between the brain and the immune system in health, aging and disease, Schwartz’s team has developed immune-based therapy to treat Alzheimer’s disease and potentially other forms of dementia. The licensed intellectual property was given to a small biopharma, ImmuneBrainCheckpoint.

Clinical trials are now underway in Israel, the UK and the Netherlands to determine whether immunotherapy can arrest or slow down the advance of Alzheimer’s disease and make it a chronic, treatable disease.

Schwartz was born in Tel Aviv to a Holocaust survivor father and a mother from Tiberias whose family had been in Israel for several generations. Growing up in the state’s early years in Holon, she was identified by her teachers as a student particularly interested in science.

“Back when I was 10 or 11, I was in a group of children who loved science. Our teacher took us to visit the Weizmann Institute, and I felt like this was the ivory tower of knowledge, the garden of wisdom. I told myself that that was the place I wanted to be. But I didn’t know how I could do that. My parents didn’t have any advanced education, and I had no one in my family who could mentor me,” Schwartz recalled.

The entrance to the Weizmann Institute of Science in Rehovot, April 20, 2020. (Yossi Aloni/Flash90)

Her dream came true when she arrived at the Weizmann Institute in the early 1970s to pursue a doctoral degree in immunology after having completed a bachelor’s degree in chemistry at the Hebrew University of Jerusalem. Schwartz, who is married to a professor of chemistry and has four children and eight grandchildren, has been at the Weizmann Institute ever since.

The Times of Israel asked Schwartz about her fortitude, what it has been like to be woman in a male scientists’ world, and what receiving the Israel Prize means to her.

How have you dealt with having to fight, to go against the grain?  It’s been many years of your standing your ground against fellow scientists telling you that you were wrong.

It was difficult with the scientific community in my field. But I felt that the more pieces I would add to the puzzle, the more convincing it would be. It was difficult, but it was my responsibility to bring more data to convince the opposition and I was hoping that others would join me and repeat my work, which was happening. So, it took time. In the early stage, it was hard to get grants, and without grants, you cannot do the science. But later on, as the community started to join me, I got the most competitive grants possible.

You were not only breaking a new path but also disproving long-held dogma.

Yes. And those two things are different. It requires believing in your way, the data, the science, and having passion and dedication. I was criticized for creating the field that I did. People thought what I was doing was silly. I wasn’t investigating brain physiology or how the brain and cognition work. Other scientists thought what I was doing was bizarre.

In 2006, when it was seven or eight years after we started this journey focused on the immune system’s robust effect on cognition, I felt that I needed to continue to dive in. I was lucky to be surrounded by outstanding students and postdocs. They chose me and they believed in the science.

What has it been like to mentor your students and help produce the next generation of neuroimmunologists?

During this unique journey, I spent hours with the students and I supported and mentored them. I imparted to them my passion and love for science and the way I look at it.  There are many “offspring” from my lab who are now independent, successful professors.

What has it been like being a woman scientist of your generation?

There were already women professors when I got here. But in my generation, it was mainly men, and their wives gave up their careers to support them and raise the kids. It was very difficult at that time for men to accept that women were successful. Of course, it didn’t justify the way they treated women. It was a time of male chauvinism and misogyny, even.

I never wanted to tell anyone I was not coming to the lab because one of my children was sick. It was not accepted at that time to stay home so I used to have a babysitter all day long, and when the kids were old enough for kindergarten, I had a babysitter on alert. I would get to the lab at 8 a.m., go home to be with the family from 5 to 9 p.m., and then go back to the lab for the rest of the evening. I didn’t want to provide any justification to be used against me. I wanted to compete with men without raising the issue or agenda.

What does being chosen for the Israel Prize mean to you?

I think it’s a [milestone] in my career. I’m excited about it because this is the highest Israel can give. It’s a milestone and I am excited about it. But I remain the same scientist now as I have always been. I continue to work because we have a clinical study, and I’m really excited about it and it has created a platform to understand additional diseases like ALS and Creutzfeldt–Jakob disease.

What are the biggest lessons you have learned from your work?

If you take everything for granted you can go very far but make many mistakes. You must be careful about what you learn. Make sure it fits with the facts. Look at the data and ask yourself what it tells you, because you may discover new things.

I think curiosity-driven research is far better than trial and error. Curiosity-driven research can bring you to mechanism-driven treatment. This is what excites me the most.

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