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, Harvard Medical School (HMS) in Boston and Clalit Research Institute in Tel Aviv are launching a joint precision medicine effort, enabled by a donation from the Berkowitz family.

The gift — the amount of which remains undisclosed at the donors’ request — 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 also will feature a clinical component that, in addition to research, will provide diagnosis and care for patients with rare, undiagnosed, and hard-to-treat conditions.

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, chair of the Department of Biomedical Informatics in the Blavatnik Institute at HMS, and Ran Balicer, founding director of the Clalit Research Institute and chief innovation officer of Clalit Health Services.

“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,” said George Q. Daley, dean of Harvard Medical School. “The scientific and educational paths forged by this collaboration and the medical insights enabled by these efforts will ripple beyond borders and across generations.”

“A synergy exists between the aspiration for innovative insights and the desire to improve clinical care,” said Eli Cohen, acting CEO of Clalit Health Services. “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.”

“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,” said Ivan Berkowitz. “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.”

Greater than the sum of its parts

The collaboration will bring together — and amplify — each institution’s traditional strengths.

Harvard Medical School’s Department of Biomedical Informatics is a powerhouse in the fields of data science, machine learning, and computational biomedicine. Part of Israel’s largest health insurance and medical provider, Clalit Research Institute is a global leader in translational science and innovation, applying Clalit’s 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.

“The ideal of precision medicine is not new. Providing the right care to the right patient at the right time has tantalized and bedeviled physicians for many decades, perhaps centuries,” said Kohane. “This ideal is now being brought closer to reality through visionary philanthropy that will fuel research and education at our two institutions and magnify each of their strengths.”

For example, researchers will be able to look for anything from telltale patterns in how individuals with the same disease respond to certain treatments and pinpoint subtle shifts in particular biomarkers that may indicate a patient’s risk for disease relapse.

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 Harvard Medical School 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 ripple beyond borders and benefit people across the globe.

Precision medicine has been described as care that takes into account individual variability to inform the most individualized treatment for each patient. As early as the 19th century, Sir William Osler, one of the founding fathers of modern medicine, cautioned his acolytes that the good physician treats the disease, while the great physician treats the patient with the disease. New insights into human biology, genetics, genomics, big-data science, clinical medicine, and computation have given Osler’s words a new meaning and 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 disease, 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 a patient would respond to a given treatment based on their genomic profile and choosing the best targeted medication for that patient. Done right, precision medicine could enable tailored predictions of disease well into the future, long before it manifests clinically.

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