Berkowitz Family

Why does SARS-CoV-2 shapeshift wildly from one person to the next, causing barely a sniffle in some but raging, lethal infections in others? Why do people diagnosed with the same cancer and receiving identical treatments have vastly different outcomes?

Untangling the precise factors that underlie such medical mysteries can illuminate individualized treatments based on a person’s genetic predispositions, immune profile, health history, and lifestyle. Such insights can propel forward the science and practice of precision medicine and have a profound effect on human health.

Now, in a decisive step forward on this quest, Clalit Research Institute in Tel Aviv, Israel, and Harvard Medical School are launching a joint precision medicine effort, enabled by a donation from the Berkowitz family. The gift will establish The Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.

The program will have two arms: The Ivan and Francesca Berkowitz Family Living Laboratory at HMS and The Ivan and Francesca Berkowitz Family Precision Medicine Clinic at Clalit. The two arms will work together to conduct joint research. The Clalit arm will also feature a clinical component that will provide diagnosis and care for patients with rare, undiagnosed, and hard-to-treat conditions.

“It is our hope that through this effort, we can harness the strength of both Harvard Medical School and Clalit in a way that will allow this collaboration to produce enormous benefits to both health and medical care globally,” Ivan Berkowitz says. “We are very happy to be one leg of this three-legged stool—the technology and medicine, the health care system, and, ultimately, the philanthropy, which makes it all happen.”

The research arm of the initiative will focus on generating insights from data and translating them into frontline clinical interventions. Under its educational arm, it will train the next generation of biomedical informaticians and computational biologists. The work will be led jointly by Isaac Kohane, MD, PhD, the Marion V. Nelson Professor and chair of the Department of Biomedical Informatics (DBMI) in the Blavatnik Institute at HMS, and Ran Balicer, MD, PhD, MPH, founding director of the Clalit Research Institute and chief innovation officer of Clalit Health Services, Israel’s largest health insurance and medical provider.

“This work, powered by the passion and vision of the Berkowitz family, is an example of cross-pollination across countries, across institutions, and across disciplines,” says HMS Dean George Q. Daley, AB ’82, MD ’91, PhD. “The scientific and educational paths forged by this collaboration and the medical insights enabled by these efforts will ripple beyond borders and across generations.”

Eli Cohen, acting CEO of Clalit Health Services, says: “A synergy exists between the aspiration for innovative insights and the desire to improve clinical care. The new initiative driven by the foresight of the Berkowitz family will achieve both aims in full alignment with Clalit’s strategy to allow every patient personalized effective care, while achieving a profound effect on science and clinical care globally.”

The collaboration will bring together—and amplify—each institution’s traditional strengths. The DBMI is a powerhouse in the fields of data science, machine learning, and computational biomedicine. Clalit Research Institute is a global leader in translational science and innovation, applying Clalit Health Services’ decades-long unique data repositories and Israel’s top data-science talent to redesign and transform clinical care for the benefit of Clalit’s 4.7 million members.

Under the agreement, Clalit will set up Israel’s first precision medicine clinic dedicated to identifying tailored therapies for patients in whom no standard treatment has proven effective. The clinic will also work to untangle medical mysteries in patients with undiagnosed diseases—an approach modeled after the U.S. Undiagnosed Diseases Network, for which HMS is a national coordinating center led by Kohane.

While the most immediate impact of the clinic’s work will be for patients in Israel, the long-range goal is to yield insights and fuel therapies that benefit people across the globe.

Precision medicine’s promise
Precision medicine has been described as care that takes into account individual variability to inform the most individualized treatment for each patient. New insights into human biology, genetics, genomics, big-data science, clinical medicine, and computation have brought precision medicine ever closer to reality. For example, scientific advances in the past 20 years have transformed the treatment of several types of cancers and led to the design of targeted therapies based on individualized genomic profiles for lung cancer, breast cancer, and melanoma.

These successes in cancer therapy offer a potent illustration of the promise of precision medicine, but other conditions are also ripe for similar study and targeted approaches—metabolic disorders such as Type 2 diabetes, various forms of cardiovascular illness, and immune diseases, including autoimmune conditions such as rheumatoid arthritis and Type 1 diabetes.

The promise of precision medicine goes beyond the ability to forecast how patients would respond to given treatments based on their genomic profiles and choosing the best targeted medication accordingly. Done right, precision medicine could enable tailored predictions of disease well into the future, long before it manifests clinically.

“The many synergies of this collaboration will allow us to realize the vision of precision medicine and move toward a future of predictive medicine, where the power to anticipate medical risk can prevent people from getting sick in the first place,” says Ben Reis, PhD, assistant professor of pediatrics at Boston Children’s Hospital (BCH), affiliate faculty member in the DBMI, and director of the Predictive Medicine Group at the BCH Computational Health Informatics Program. “The Berkowitzes’ generous gift creates profound opportunities both for Harvard and our partners at Clalit. We look forward to realizing the enormous potential of this transformational opportunity for the benefit of patients worldwide.”

Lab to clinic and beyond
Researchers at Clalit’s Precision Medicine Research Clinic will work side by side with scientists at the Living Laboratory in the DBMI at HMS. Real-life data from millions of patients accumulated over decades, when analyzed in aggregate, can provide invaluable insights about the real-time behavior of a disease, but it could yield deeper answers as well.

“Such insights can beget further ones by compelling researchers to ask questions about the origins of disease—the fundamental mechanisms that give rise to dysfunction,” says Shay Ben-Shachar, director of precision medicine and genomics at Clalit Research Institute. “This is the true long-term value of this effort.”

The idea that gleaning insights from a single patient or a handful of patient cases could be amplified and propagated to help countless others captivated the imagination of Adam Berkowitz, son of Ivan and Francesca, and the youngest of three children.

“This is an opportunity to extract knowledge from very specific cases and generalize these insights to help people in Israel and around the world, and all we need is one of those insights to power a general extract,” Adam Berkowitz says. “That’s the beauty and the true power of data. The fact that with a single insight you could potentially help millions.” The vision and excitement are echoed by Adam’s siblings, Elizabeth Lewinsohn and Eric Berkowitz. “The rewards of this innovative collaboration for global health care could be immense,” Lewinsohn says.

Eric Berkowitz, the oldest of the three, says, “Through data-driven insights, this historic collaboration will lead to new knowledge, novel treatments and cures, and, ultimately, to a better quality of life.”

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Training the next generation of leaders

Harvard Medical School will share its expertise and knowledge with bioinformatics scientists in Israel through three scholarly exchanges:

• A cadre of postdoctoral trainees from Israel will be selected as Berkowitz Postdoctoral Fellows to receive training in research at HMS, guided by HMS faculty serving as research mentors and educators. These fellows will conduct part of their work at HMS and part of it at Clalit Research Institute, forging stronger training and research ties between the two institutions.;
• A group of clinical researchers from Israel, chosen through a nationwide search, will attend a summer bootcamp in biomedical informatics at HMS. During this three-month program, these Berkowitz Scholars will study the latest precision medicine approaches and methods, with a focus on designing and leading their own clinical research projects upon returning to Israel.
• Select faculty members from HMS who are serving as mentors in the postdoctoral program will have the chance to work directly with Clalit researchers, with the option of serving in residence at Clalit.