Thousands of COVID-19 cases and deaths in California, Oregon, and Washington between March and December 2020 may be attributable to increases in fine particulate air pollution (PM2.5) from wildfire smoke, according to a new study co-authored by researchers at Harvard T.H. Chan School of Public Health.

The study is the first to quantify the degree to which increases in PM2.5 pollution during the wildfires contributed to excess COVID-19 cases and deaths in the U.S. It will be published online Friday in Science Advances.

“The year 2020 brought unimaginable challenges in public health, with the convergence of the COVID-19 pandemic and wildfires across the western United States. In this study we are providing evidence that climate change — which increases the frequency and the intensity of wildfires — and the pandemic are a disastrous combination,” said Francesca Dominici, the Clarence James Gamble Professor of Biostatistics, Population and Data Science at the Harvard Chan School and senior author of the study.

In 2020, huge wildfires swept across the western U.S., including some of the largest ever in California and Washington. Wildfires produce high levels of fine particulate matter, which has been linked with a host of negative health outcomes, including premature death, asthma, chronic obstructive pulmonary diseases (COPD), and other respiratory illnesses.

The researchers — from the Harvard Chan School, the John A. Paulson School of Engineering and Applied Sciences, and the Environmental Systems Research Institute in Redlands, Calif. — built and validated a statistical model to quantify the extent to which wildfire smoke may have contributed to excess COVID-19 cases and deaths in the three states that bore the brunt of the 2020 wildfires. They looked at the connection between county- and daily-level data on PM2.5 air concentrations from monitoring data, wildfire days from satellite data, and the number of COVID-19 cases and deaths in 92 counties, which represented 95 percent of the population across California, Oregon, and Washington. The researchers accounted for factors such as weather, population size, and societal patterns of social distancing and mass gatherings.

The study found that from Aug. 15 to Oct. 15, 2020, when fire activity was greatest, daily levels of PM2.5 during wildfire days were significantly higher than on non-wildfire days, with a median of 31.2 micrograms per cubic meter of air (µg/m3) versus 6.4 (µg/m3). In some counties, the levels of PM2.5 on wildfire days reached extremely high levels. For instance, on Sept. 14-17, 2020, Mono County, California, experienced four days in a row with PM2.5 levels higher than 500 µg/m3 as a result of the Creek Fire. Such levels are deemed “hazardous” by the U.S. Environmental Protection Agency.

Wildfires amplified the effect of exposure to PM2.5 on COVID-19 cases and deaths for up to four weeks after the exposure, the study found. In some counties, the percentage of the total number of COVID-19 cases and deaths attributable to high PM2.5 levels was substantial.

On average across all counties, the study found that a daily increase of 10 µg/m3 in PM2.5 each day for 28 subsequent days was associated with an 11.7 percent increase in COVID-19 cases, and an 8.4 percent increase in COVID-19 deaths. The biggest effects for cases were in the counties of Sonoma, California, and Whitman, Washington, with 65.3 percent and 71.6 percent increases, respectively. The biggest effects for deaths were in Calaveras, California, and San Bernardino, California, with 52.8 percent and 65.9 percent increases, respectively.

Researchers also looked at individual wildfire days and at individual counties to determine the percentage increase in COVID-19 cases and deaths in 2020 compared with what would have been expected with lower levels of PM2.5. They found that Butte, California and Whitman, Washington, had the highest percentage increases in cases (17.3 percent and 18.2 percent, respectively); and that Butte, California, and Calaveras, California, had the highest percentage increases in deaths (41 percent and 137.4 percent, respectively.) In Calaveras, roughly nine COVID-19 deaths would have been expected under lower PM2.5 levels, but the actual number was 22 — which explains the high percentage increase.

Across the three states studied, the cumulative numbers of COVID-19 cases and deaths attributable to daily increases in PM2.5 from wildfires were 19,700 and 750, respectively, the study found.

“Climate change will likely bring warmer and drier conditions to the west, providing more fuel for fires to consume and further enhancing fire activity. This study provides policymakers with key information regarding how the effects of one global crisis — climate change — can have cascading effects on concurrent global crises — in this case, the COVID-19 pandemic,” said Dominici.

Co-first authors of the study were Xiaodan Zhou of the Environmental Systems Research Institute and Kevin Josey from the Department of Biostatistics at the Harvard Chan School. Leila Kamareddine of the Department of Biostatistics at the Harvard Chan School also contributed, as did Miah C. Caine and Loretta J. Mickley from Harvard’s John A. Paulson School of Engineering and Applied Sciences, and Tianjia Liu from Harvard’s Department of Earth and Planetary Sciences.

Funding for the study came from the Environmental Protection Agency (grant 83587201-0), the National Institutes of Health (grants R01ES026217, R01MD012769, R01ES028033, 1R01AG060232-01A1, 1R01ES030616, 1R01AG066793-01R01, 1R01ES029950, and 5T32ES007142), the Alfred P. Sloan Foundation, and the Vice Provost for Research-Harvard University.

As delta surges, what can we expect if vaccination and mask-wearing rates don’t change?

According to investigators who previously developed the COVID-19 Simulator — which models the trajectory of the illness in the U.S. at the state and national levels — the combination of variant’s high transmissibility, low vaccination coverage in several regions, and more relaxed attitudes toward social distancing will likely lead to a surge in COVID-19–related deaths in at least 40 states.

And if current social distancing behaviors and vaccination rates remain unchanged, the simulator predicts that in several states, daily COVID-19–related deaths could exceed the peak seen in early 2021.

The researchers applied the tool to potential scenarios in which the COVID-19 delta variant becomes dominant in every state. Its analysis, published on the preprint server medRxiv, showed an additional 157,000 COVID-19-related deaths could occur across the U.S. between August 1 and December 31. It projected approximately 20,700 delta-related deaths in Texas, 16,000 in California, 12,400 in Florida, 12,000 in North Carolina, and 9,300 in Georgia. In contrast, the projected number of COVID-19-related deaths would remain below 200 in New Jersey, Massachusetts, Connecticut, Vermont, and Rhode Island.

The team’s projections are updated weekly by incorporating vaccination rates and social-distancing measures in each state, and the latest results can be found at the simulator website.

“These projections should serve as a warning sign, especially in states that could have higher daily COVID-19 deaths than their previous peaks,” said lead author Jagpreet Chhatwal, associate director of Massachusetts General Hospital’s Institute for Technology Assessment and an assistant professor at Harvard Medical School. “We also hope that our projections can help policymakers bring back mask mandates and further advocate for COVID-19 vaccines.”

Researchers at Beth Israel Deaconess Medical Center are testing a new approach to fighting COVID-19, using a repurposed antiviral AIDS drug for at-home treatment during the first days of symptoms in hopes of slowing the virus early and heading off hospitalization, intensive care, and death.

The nationwide clinical trial is being led by Nathan Shapiro, professor of emergency medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, along with investigators at Vanderbilt University and the University of Colorado. They are hoping to enroll 600 volunteers with early COVID-19 symptoms for the study to see whether daily doses of Kaletra, a widely used AIDS drug that combines the antiretrovirals lopinavir and ritonavir, can reduce the number of COVID-19 cases that become serious enough to require hospitalization.

“If we can cut down on the progression to severe illness, then it would be a huge game-changer because we would be cutting down on disease. Reducing severity will also cut down on resource utilization, hospitalization, and the subsequent morbidity that happens when you are sick enough to get put on a ventilator or wind up in the ICU [intensive care unit],” Shapiro said.

Because the drug is already being used to fight AIDS around the world, Shapiro said, positive results would mean that there are already stores and a production pipeline so it could be rapidly deployed. The effort is following up on an earlier trial of the drug in China that, while it didn’t show efficacy against the coronavirus at later stages, did provide some indication that it was working. For that trial, Shapiro said, the drug was given to patients around day 13.

The new trial seeks to begin intervention within the first week after symptoms appear and continue treatment for two weeks in hopes that the drug will keep viral load low enough that patients avoid hospitalization and intensive care.

Shapiro believes that finding an effective way to intervene early in the course of the illness would provide physicians and their patients with a potentially powerful tool. Among the unknowns in evaluating the strategy, he said, is whether reducing viral load will also reduce the virus’ spread, potentially by reducing the amount of virus in the body to be shed to others.

“Is this a potential game-changer if we can intervene at this stage of the illness? Without a doubt,” Shapiro said. “Whether this is the particular drug that will be the game-changer or if it’ll be a different drug, that’s the hypothesis that we’re testing, and we would look to test in sequence: If this drug doesn’t work, we would seek to bring in another.”

The trial, called TREAT NOW, for Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window, is being conducted in an entirely touchless format, Shapiro said. The team informs patients about it via phone or videoconference, and participants give consent electronically, via email or text. The medication is shipped overnight so subjects can begin treatment the next day. Researchers follow up with participants daily, recording symptoms and side effects. Shapiro said researchers will gain a window into the ailment’s progression — including whether symptoms abate earlier than expected.

Consuming higher amounts of vitamin D — mainly from dietary sources — may help protect against developing young-onset colorectal cancer or precancerous colon polyps, according to the first study to show such an association.

The study, recently published online in the journal Gastroenterology, by scientists from Dana-Farber Cancer Institute, the Harvard T.H. Chan School of Public Health, and other institutions, could potentially lead to recommendations for higher vitamin D intake as an inexpensive complement to screening tests as a colorectal cancer prevention strategy for adults younger than age 50.

While the overall incidence of colorectal cancer has been declining, cases have been increasing in younger adults — a worrisome trend that has yet to be explained. The authors of the study, including senior co-authors Kimmie Ng of Dana-Farber, and Edward Giovannucci of the T.H. Chan School, noted that vitamin D intake from food sources such as fish, mushrooms, eggs, and milk has decreased in the past several decades. There is growing evidence of an association between vitamin D and risk of colorectal cancer mortality. However, prior to the current study, no research has examined whether total vitamin D intake is associated with the risk of young-onset colorectal cancer.

“Vitamin D has known activity against colorectal cancer in laboratory studies. Because vitamin D deficiency has been steadily increasing over the past few years, we wondered whether this could be contributing to the rising rates of colorectal cancer in young individuals,” said Ng, director of the Young-Onset Colorectal Cancer Center at Dana-Farber. “We found that total vitamin D intake of 300 IU per day or more — roughly equivalent to three 8-oz. glasses of milk — was associated with an approximately 50 percent lower risk of developing young-onset colorectal cancer.”

The results of the study were obtained by calculating the total vitamin D intake — both from dietary sources and supplements — of 94,205 women participating in the Nurses’ Health Study II (NHS II). This study is a prospective cohort study of nurses aged 25 to 42 years that began in 1989. The women are followed every two years by questionnaires on demographics, diet and lifestyle factors, and medical and other health-related information. The researchers focused on a primary endpoint — young-onset colorectal cancer, diagnosed before 50 years of age. They also asked on a follow-up questionnaire whether they had had a colonoscopy or sigmoidoscopy where colorectal polyps (which may be precursors to colorectal cancer) were found.

From 1991 to 2015, the researchers documented 111 cases of young-onset colorectal cancer and 3,317 colorectal polyps. Analysis showed that higher total vitamin D intake was associated with a significantly reduced risk of early-onset colorectal cancer. The same link was found between higher vitamin D intake and risk of colon polyps detected before age 50.

The association was stronger for dietary vitamin D — principally from dairy products — than from vitamin D supplements. The study authors said that finding could be due to chance or to unknown factors that are not yet understood.

Interestingly, the researchers didn’t find a significant association between total vitamin D intake and risk of colorectal cancer diagnosed after age 50. The findings were not able to explain this inconsistency, and the scientists said further research in a larger sample is necessary to determine if the protective effect of vitamin D is actually stronger in young-onset colorectal cancer.

In any case, the investigators concluded that higher total vitamin D intake is associated with decreased risks of young-onset colorectal cancer and precursors (polyps). “Our results further support that vitamin D may be important in younger adults for health and possibly colorectal cancer prevention,” said Ng. “It is critical to understand the risk factors that are associated with young-onset colorectal cancer so that we can make informed recommendations about diet and lifestyle, as well as identify high risk individuals to target for earlier screening.”

The study was funded by grants from the U.S. National Institutes of Health and the Department of Defense, by the American Cancer Society Mentored Research Scholar Grant, and by the Project P Fund.

Ng’s disclosures include research funding from Pharmavite, Revolution Medicines, Janssen, and Evergrande Group; Advisory boards for Array Biopharma, Seattle Genetics, and BiomX; and consulting for X-Biotix Therapeutics.

Medical experts called the idea that a coronavirus vaccine would allow life to immediately return to normal “magical thinking,” describing instead a slow process of inoculating the public during which public health measures like masking and distancing would still be needed.

Anthony Fauci, the nation’s top infectious disease expert and a leader of America’s coronavirus response, said Monday a vaccine is “just around the corner” and that it represents the clearest path toward ending the U.S. coronavirus pandemic. Even so, former Harvard Medical School professor and former World Bank President Jim Yong Kim warned against pinning hopes on it for a quick end to the pandemic.

Even if a vaccine is 75 percent effective, Kim said, skepticism about it may mean that as little as half of the population would take it. So it would fall far short of reaching “herd immunity” threshold, at which enough people are protected from infection to interrupt transmission.

“We’re not at herd immunity with that level, so you still need to chase down every single outbreak,” Kim said.

Kim, Fauci, and Paul Farmer, Harvard’s Kolokotrones University Professor of Global Health and Social Medicine, agreed that the basic public health measures that have been employed since the beginning of the pandemic will still be needed. In addition, Kim called for added investment in those measures, expressing astonishment that those steps were left out of stimulus packages that focused instead on mitigating economic harm.

“Why would you send $6 trillion or $5 trillion out into the world and really put in nothing for the only thing that has actually worked to stop the virus anywhere, which is the full public health response: social distancing with masks, testing, tracing, isolation and, of course, treatment of the sick?” Kim said, adding that business leaders may still not appreciate those measures’ importance. “I don’t think they understand — these business leaders — how difficult it is, even when we get a vaccine or better therapeutics, to deal with this particular virus. That’s what worries me. We still have not emerged from the magical thinking that says, ‘Once we get a vaccine, this is over.’”

Fauci said, however, the prospect of gaining a vaccine plays a critical psychological role in the fight, even if success may not mark a clear end to the problems. Many are feeling fatigued by the months of strict daily adherence to public health measures. Having the sense that a vaccine is near, he said, may be important in encouraging people to remain vigilant.

Farmer agreed the feeling of making progress is important and that we have learned much from earlier pandemics, specifically Ebola in West Africa and the Democratic Republic of the Congo — where there was resistance to an Ebola vaccine — on how to control outbreaks and promote vaccines.

“We still know the basics of what we must do to bring this epidemic under control, and that also includes preparing people for a vaccine,” Farmer said. “I have some optimism about this. There is a lot of mistrust, a lot of miscommunication that needs to be cleared up. Some of this will last well into the coming year, but there is a good chance that we can prepare communities for — and enlist the support of communities — in rolling out this vaccine.”

Farmer, Fauci, and Kim appeared at a webcast event on Monday, “COVID-19 Reflections and Updates,” examining lessons from the pandemic so far. Organized by Harvard Medical School’s Department of Global Health and Social Medicine, the event was hosted by HMS Dean George Daley, who said that focusing on the prospect for a biomedical “silver bullet” in the form of a vaccine or therapeutic risks losing sight of the importance of social, political, public health, and other society-wide systems that have affected the course of the pandemic here.

A new study by investigators from Harvard-affiliated Brigham and Women’s Hospital found a potential direct link between exposure to parental smoking during childhood and increased risk of seropositive rheumatoid arthritis (RA) later in life.

Researchers utilized established longitudinal data from 90,923 women in the Nurses’ Health Study II (NHSII) to elucidate the relationship between passive smoking exposure and incident RA. Passive exposure was broken down into three categories, including maternal smoking during pregnancy, parental smoking during childhood, and years lived with smokers since age 18. Even with personal smoking accounted for, passive exposure to parental smoking during childhood was found to increase risk of incident seropositive RA by 75 percent. Findings are published in Arthritis & Rheumatology.

“There has been intense interest in mucosal lung inflammation from personal smoking as a site of RA pathogenesis,” said senior author Jeffrey A. Sparks of the Department of Medicine at the Brigham. “But the majority of RA patients aren’t smokers, so we wanted to look at another inhalant that might precede RA.”

RA is an inflammatory disease characterized by arthritis at multiple joints and is associated with morbidity and mortality outcomes. Many people with RA have signs of lung inflammation, and while genetic and environmental factors contribute to risk of developing RA, smoking has long been implicated as a key RA risk factor. Personal (active) smoking is the most well-established environmental risk factor associated with RA, with passive smoking left relatively unexplored.

To link passive smoking and incident RA more conclusively, Sparks and colleagues used data from NHSII questionnaires collected biennially between 1989 and 2017 from 90,923 women aged 35-52 years. Researchers used participant medical records to confirm incident RA and serostatus. Statistical modeling was then used to estimate the direct effect of each passive smoking exposure on RA risk, as well as to control for other factors such as personal smoking.

A 75 percent higher risk of RA was found in individuals who experienced passive childhood exposure to parental smoking. This risk increased in participants who themselves became active smokers. Over the median follow-up of 27.7 years, 532 women in the cohort developed confirmed incident RA cases — the majority (352) of which were seropositive (positive for RA autoantibodies). Maternal smoking during pregnancy and years lived with smokers beyond age 18 showed no significant association with incident RA risk.

Although the all-female nurse participant pool led to high response rates and retention, the study is limited by the absence of men. The team intends to continue with longitudinal studies that encompass both men and women, as to provide critical insight into other rheumatoid conditions and even other autoimmune diseases.

“Our findings give more depth and gravity to the negative health consequences of smoking in relation to RA, one of the most common autoimmune diseases,” said lead and co-corresponding author Kazuki Yoshida of the Brigham’s Division of Rheumatology, Inflammation and Immunity. “This relationship between childhood parental smoking and adult-onset RA may go beyond rheumatology — future studies should investigate whether childhood exposure to inhalants may predispose individuals to general autoimmunity later in life.”

This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) under award number K23 AR069688 to Jeffrey Sparks. This work was additionally supported by the Rheumatology Research Foundation R Bridge Award, and by the National Institutes of Health (award numbers L30 AR066953, K24 AR052403, R01 AR049880, R01AR057327, R01 AR119246, R01 HL034594, P30 AR070253, P30 AR072577, P30 AR069625, UM1CA186107, U01 HG008685, 1OT2OD026553, and R03 AR075886). Kazuki Yoshida was supported by the Rheumatology Research Foundation K Bridge Award, Brigham and Women’s Hospital Department of Medicine Fellowship Award, and K23 AR076453 (NIAMS). Nurses’ Health Study II was supported by the National Institutes of Health (U01 CA176726, R01CA67262, and U01 HL145386).

Look away, America. For your own good, look away. Everything will still be there when you come back. Even once the vote counting’s done, there’ll be the recounting, and the tag-along lawsuits.

So take a walk, take a breath, take a break from the election drama unspooling at a pace better suited to a garden slug than an advanced nation’s sophisticated vote-counting system. So, psychologists say, maybe you should get off the smartphone, get back to work, and get some perspective. Though weighty issues like climate change, the economy, and the COVID pandemic also are on the table, the science of “affective forecasting” assures us that we’re lousy judges of our own future emotions on such matters.

“One of the things that happens with uncertainty is we often don’t think realistically about the outcome, and we tend to think catastrophically. So, you’re already thinking that if your candidate loses it’s going to be awful, it’s going to be unbearable, it’ll be disastrous,” said psychologist Shelley Carson, a lecturer at the Harvard Extension School and associate of the Faculty of Arts and Sciences’ Psychology Department. “We overestimate how this event — or any event — is going to affect our happiness in the future.”

Carson said she normally views the U.S. as a pretty stable nation, one whose national character readily absorbs the ups and downs that make history. But she and Jacqueline Sperling, instructor in psychology in Harvard Medical School’s Department of Psychiatry, said that these times are not normal and, if anxiety were measured as a disease, the election worries would compound and aggravate the existing concerns about the ongoing COVID-19 pandemic and resultant lost jobs.

With the coronavirus pandemic worsening again, the holidays are going to be a challenge this year, so a Harvard epidemiologist offered something of a survival guide for navigating travel, family gatherings, and other autumnal activities.

William Hanage, an associate professor of epidemiology at the Harvard T.H. Chan School of Public Health, said it’s important to remember the advice we’ve already been given about limiting the size of gatherings, using masks, avoiding crowds, and sanitizing hands. He also urged people to remember the importance of adequate ventilation, even if it means cracking open doors and windows when sitting down to a family dinner in November or December.

“It may be somewhat cold in the room, but this is an opportunity to get out those fall sweaters we all like to wear,” Hanage said during a Facebook Live event co-sponsored by The Forum at Harvard T.H Chan School of Public Health and PRI’s “The World.”

Cases of COVID-19 have been rising nationally over the last few weeks, with more than 10 million by Nov. 9, while estimated deaths reached 238,000, according to the Centers for Disease Control and Prevention.

Coronavirus transmission is heightened in poorly ventilated indoor spaces, where people aren’t distancing or using masks, Hanage said. That explains recent outbreaks linked to restaurant dining and highlights the upcoming hazards of the holidays, when far-flung families gather for meals.

“We can see the way holidays have the potential to be a real serious problem in pandemic transmission,” Hanage said. He offered this advice for the weeks ahead:

• Travel: Welcoming college students home for the holidays doesn’t have to be a risky endeavor. Hanage said some institutions are doing a good job keeping outbreaks off campus and, when they do occur, stamping them out before they spread widely. The result, he said, is that some campuses have lower incidence of the disease than their surrounding communities. Holiday travelers should consider getting tested before they leave and, in the event of a negative test, refrain from viewing it as a free pass — false negatives are possible, and the virus can be picked up en route. That means it’s still important that travelers use masks, distance, sanitize their hands, and take other routine precautions.
• Thanksgiving and beyond: When gathering for family dinners, Hanage said it’s important to remember that the risk of developing a serious illness increases rapidly for those over 40. A 50-year-old’s risk of dying from COVID-19 is 200 times higher than normal, Hanage said. It has long been recognized that a surge in cases of invasive pneumococcal disease — which can cause pneumonia or meningitis — in older individuals typically occurs after the holidays, likely due to contact with younger people with mild illness. That highlights the importance of ensuring that any gathering takes place in a safe setting, preferably one with plenty of ventilation, even if it means opening a window six inches despite chilly outdoor temperatures.

Hanage said he understands that “pandemic fatigue” is real and acknowledged that he’s felt it himself. But he said that people don’t have to dread a future of lockdowns if they accept that this once-in-a-century event can be managed using less-stringent steps, like masking and distancing, applied universally, to keep cases low and avoid straining the health system capacity.

“We have a long winter ahead of us and I’m not going to say it’s going to be fun,” Hanage said.

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.

To read the full release.

Third in a series that taps the expertise of the Harvard community to examine the promise and potential pitfalls of the coming age of artificial intelligence and machine learning.

The news is bad: “I’m sorry, but you have cancer.”

Those unwelcome words sink in for a few minutes, and then your doctor begins describing recent advances in artificial intelligence, advances that let her compare your case to the cases of every other patient who’s ever had the same kind of cancer. She says she’s found the most effective treatment, one best suited for the specific genetic subtype of the disease in someone with your genetic background — truly personalized medicine.

And the prognosis is good.

It has taken time — some say far too long — but medicine stands on the brink of an AI revolution. In a recent article in the New England Journal of Medicine, Isaac Kohane, head of Harvard Medical School’s Department of Biomedical Informatics, and his co-authors say that AI will indeed make it possible to bring all medical knowledge to bear in service of any case. Properly designed AI also has the potential to make our health care system more efficient and less expensive, ease the paperwork burden that has more and more doctors considering new careers, fill the gaping holes in access to quality care in the world’s poorest places, and, among many other things, serve as an unblinking watchdog on the lookout for the medical errors that kill an estimated 200,000 people and cost $1.9 billion annually.

“I’m convinced that the implementation of AI in medicine will be one of the things that change the way care is delivered going forward,” said David Bates, chief of internal medicine at Harvard-affiliated Brigham and Women’s Hospital, professor of medicine at Harvard Medical School and of health policy and management at the Harvard T.H. Chan School of Public Health. “It’s clear that clinicians don’t make as good decisions as they could. If they had support to make better decisions, they could do a better job.”

Years after AI permeated other aspects of society, powering everything from creepily sticky online ads to financial trading systems to kids’ social media apps to our increasingly autonomous cars, the proliferation of studies showing the technology’s algorithms matching the skill of human doctors at a number of tasks signals its imminent arrival.

“I think it’s an unstoppable train in a specific area of medicine — showing true expert-level performance — and that’s in image recognition,” said Kohane, who is also the Marion V. Nelson Professor of Biomedical Informatics. “Once again medicine is slow to the mark. I’m no longer irritated but bemused that my kids, in their social sphere, are using more advanced AI than I use in my practice.”

But even those who see AI’s potential value recognize its potential risks. Poorly designed systems can misdiagnose. Software trained on data sets that reflect cultural biases will incorporate those blind spots. AI designed to both heal and make a buck might increase — rather than cut — costs, and programs that learn as they go can produce a raft of unintended consequences once they start interacting with unpredictable humans.

“I think the potential of AI and the challenges of AI are equally big,” said Ashish Jha, former director of the Harvard Global Health Institute and now dean of Brown University’s School of Public Health. “There are some very large problems in health care and medicine, both in the U.S. and globally, where AI can be extremely helpful. But the costs of doing it wrong are every bit as important as its potential benefits. … The question is: Will we be better off?”

Many believe we will, but caution that implementation has to be done thoughtfully, with recognition of not just AI’s strengths but also its weaknesses, and taking advantage of a range of viewpoints brought by experts in fields outside of medicine and computer science, including ethics and philosophy, sociology, psychology, behavioral economics, and, one day, those trained in the budding field of machine behavior, which seeks to understand the complex and evolving interaction of humans and machines that learn as they go.