If you’re looking for a miracle drug that cuts heart attack and diabetes risk by 80 and 90 percent, respectively, and also reduces the danger of cancer, stroke, and late-life cognitive decline, just close the medicine cabinet door.
Look in the mirror instead.
Despite recent headlines on potentially revolutionary cholesterol-lowering drugs, panelists in a recent forum at the Harvard T.H. Chan School of Public Health said that the most dramatic health effects will continue to come from the lifestyle choices we make every day.
Eat a healthy diet, don’t pack on the pounds, get regular exercise, and don’t smoke. That recipe for the medical miracle is reliable enough that the panelists said it should be taught in grade school and through health-education campaigns. And research, they suggested, should be directed toward figuring out how to deliver that message in ways that get more people to pay attention.
“The evidence is quite strong that lifestyle factors will go a long way, but we don’t know how to promote a healthy lifestyle, how to get people to do it,” said JoAnn Manson, the Michael and Lee Bell Professor of Women’s Health at Harvard Medical School (HMS). “We need some creative solutions, we need more research to understand how to engage healthy lifestyles in the population.”
Frank Sacks, a professor of cardiovascular disease prevention at the Harvard Chan School and Harvard-affiliated Brigham and Women’s Hospital, agreed with Manson, saying that a 75-year-old who adheres to recommended lifestyle measures — getting enough exercise, eating a healthy diet, and maintaining a normal body weight — will likely experience no cognitive decline for at least the next 10 years.
“We have a very optimistic message,” Sacks said, “we just have to deliver it.”
Panelists also included Patrick O’Gara, a professor of medicine at HMS and the Brigham and past president of the American College of Cardiology, and Paul Ridker, a professor of medicine and director of the Brigham’s Center for Cardiovascular Disease Prevention. The event, “Rethinking Cholesterol: Drug Developments and Lifestyle Choices,” was co-sponsored by Reuters and Harvard Health Publications and moderated by Reuters correspondent Bill Berkrot.
While lifestyle choices remain paramount as a foundation for good health, the panelists agreed that statins have been beneficial in lowering cholesterol for millions of patients. The Food and Drug Administration last summer approved the new drugs — called PCSK9 inhibitors — for those with ultra-high cholesterol because of genetic reasons, for those who have already had a heart attack or stroke, and for those for whom statins are ineffective or cause intolerable side effects.
The jury is still out, however, on whether those lower levels might help the millions of people in the broader population who routinely take statins. The new drugs reduce LDL, or “bad cholesterol,” beyond what is possible with statins. Their potential health effects — in reduced heart attacks and strokes — are being examined in an ongoing study of 60,000 people.
Even if the study does find salutary effects, questions about cost and benefit will remain, panelists said. The new drugs are expensive — $14,000 per year for a normal regimen — and, in an era of steadily rising medical costs, will likely come under scrutiny if they are recommended for a large number of people currently on statins.
Manson worried that relying on drugs to treat the nation’s health problems could encourage a scenario in which children too regularly use statins, blood pressure medicine, and diabetes drugs. Aside from the unknown effects of taking such drugs for a lifetime, the illness and cognitive decline linked to unhealthy living would continue.
“The medicines are terrific for high-risk, targeted population groups, but not the ultimate solution to the [problem of] chronic disease throughout the world,” Manson said.
To see the original article, please click here.
When Robert Farese and Tobias Walther were negotiating to join Harvard T.H. Chan School of Public Health last year as professors of genetics and complex diseases, they proposed a twist to their appointments—a joint laboratory run as an equal partnership. Although they were working in different institutions and came from different disciplines—Farese from physiology and biomedicine, Walther from cell biology and biochemistry —they had been collaborating remotely for a decade, finding fertile ground in their shared research interests, scientific values, and wide-ranging curiosity.
With research largely focused on how cells store and synthesize fat—a principle applicable to understanding obesity and its related diseases—they were keen to join a department well-known for its metabolism research. But their unusual lab arrangement might have been a hard sell in some quarters. Fortunately, Genetics and Complex Diseases Chair Gökhan Hotamisligil got it, Farese said. “He was very enthusiastic.”
At the School, the two scientists have combined their areas of expertise to give the lab the capability to “bridge anything from physics to human genetics and everything in between,” Walther said. Both contribute ideas and act as each other’s sounding board. “If I can’t convince my best science friend that something is important and should be done, then there is a serious problem with it,” said Walther. “If we’re both excited about an idea, and we’re still excited a month later, it’s probably a better idea.”
Working together, they have identified more than 200 genes that regulate storage of lipids (fatty acids and oils that store energy and provide materials needed to build and maintain cell membranes). Lipids are stored in organelles known as droplets that play an important role in metabolic function. Walther and Farese have published a growing body of work unravelling the complex biology of lipid droplets, including a paper published August 10, 2015 in Developmental Cell, which explains a principle behind the composition of proteins on the surface of the organelles.
Their efforts received a significant endorsement in May when Walther was named a Howard Hughes Medical Institute Investigator. The prestigious five-year appointment provides each investigator with his or her full salary, benefits, and a research budget. Although the award is in his name, Walther is quick to include Farese in the honor.
A fruitful meeting
Their collaboration goes back to 2005 when Farese, then a professor of medicine, and biochemistry and biophysics at the Gladstone Institutes at the University of California, San Francisco (UCSF), decided to take a sabbatical year in his colleague Peter Walter’s lab to learn about cell biology. “I wanted to learn about how to think about problems differently,” Farese said. “I got really lucky because I sat down next to Tobi.”
Walther, then a postdoctoral researcher, was equally inspired by Farese. “I was on the trajectory of being a biochemist and cell biologist,” he said. “Then this sabbatical professor showed up who came from a different discipline and started talking about all these problems that had a strong overlap with my interests.”
Ten years later, they both agree that the collaboration has likely changed how they approach their research and what they produce. “It would be like if he wrote a song and I wrote a song and then we wrote one together,” said Farese. “All three would be completely different.”
Among the shared scientific values that bring them together is an emphasis on working towards a legacy focused on training the next generation of researchers and translating scientific contributions into clinical practice and public health.
Walther said, “We want to explain fundamental mechanisms and how they impact human health and disease. We’re not satisfied with scratching on the surface, and we will challenge each other and our lab members on clarity. I think we both have a pretty high allergy against intellectual mud.”
In addition to their work on metabolism research, Walther and Farese are working on understanding the mechanisms underlying neurological and neurodegenerative diseases. When asked where they hope to be in five years, Walther leaves the door open for the serendipity of discovery.
“The world is full of wonders,” Walther said, quoting Walter. “Every time you turn over a stone, there is something amazing lurking under it.”
— Amy Roeder
Photo: Kent Dayton
To see the original article, please click here
The Harvard Integrated Life Sciences (HILS) Program warmly invites you to attend the HILS 10th Anniversary Gathering: “Celebrating a Decade of Creativity, Collaboration, and Connection” on Thursday, October 8, 2015 from 1:00 p.m. – 5:00 p.m.
Featuring a keynote address by David Altshuler MD/PhD ’90 (Executive Vice-President, Global Research and Chief Scientific Officer, Vertex Pharmaceuticals), an alumni career panel, reception, and poster presentations will also be featured.
Find the full schedule and register for the event here
Don’t miss this opportunity to connect with HILS students, faculty, and alumni to celebrate Harvard’s life sciences achievements!
The current controversy about the wisdom of conducting experiments with pathogens that are genetically engineered to be more contagious presents a unique opportunity to set an effective precedent on the issue of biological experiments that carry large-scale risks, according to a Foreign Affairs article co-authored by Harvard T.H. Chan School of Public Health epidemiologist Marc Lipsitch.
In the August 31, 2015 article, Lipsitch, professor of epidemiology and director of the Center for Communicable Disease Dynamics at Harvard Chan School, and co-author David A. Relman of Stanford University noted that the U.S. government suspended funding last October for so-called “gain-of-function” research on avian flu. In such research, more contagious forms of the highly pathogenic flu would be created in the laboratory so that scientists could learn more about the genetics required for a flu strain to cause a pandemic.
The authors have been outspoken critics of such research, arguing that it poses great risks—most notably the possibility of a lab accident or deliberate misuse of extremely contagious and virulent pathogens, and that the benefits of such research could be achieved by alternative, safer means. That’s why the government imposed its funding moratorium, which is coinciding with an international deliberative process that aims to assess the risks and benefits of the research. The authors argue that the risks of future biological experiments, involving new techniques of genetic modification in which a laboratory accident could harm whole human, animal or plant populations, will be even more controversial. The flu controversy, they write, will be the first of many hard decisions about balancing the benefits of new approaches to biological research against the risks.
“The flu controversy—complex as it is—is a relatively easy test case, and it represents an opportunity to develop an international norm of safety-conscious, responsible deliberation among scientists working in these fields, and others who have a stake,” the authors wrote. “The future of biological research demands a new approach to governance, greater awareness of risk, and a suite of tools for identifying and regulating certain classes of dangerous experiments—those that pose risks to entire human, animal, or plant populations.”
Read the Foreign Affairs article: New Game, New Rules: Limiting the Risks of Biological Engineering
Dangerous pathogen research should be stopped—for good (Harvard Chan news)
Experiments with potential pandemic flu strains pose deadly risk (Harvard Chan news)
To view original article, please click here
One of the research projects of Dr. Quan Lu, Associate Professor of Environmental Genetics and Pathophysiology, at the Harvard T.H. Chan School of Public Health, will receive support through the Blavatnik Biomedical Accelerator during the next year. His is one of twelve Harvard based projects to receive funding from this organization. Dr. Lu’s research will address the challenges associated with delivering new treatments to the tissues that need them the most by testing the ability of natural microvesicles known as ARMMs to deliver large therapeutic proteins to cells. Dr. Lu and the other projects reflect the diversity of translational biomedical research at Harvard.
To see the original article with more details of all the projects being supported by the Blavatnik Biomedical Accelerator, please click here.
An unexpected new discovery—that, in people with asthma, the cells that line the airways in the lungs are unusually shaped and “scramble around like there’s a fire drill going on”—suggests intriguing new avenues both for basic biological research and for therapeutic interventions to fight the disease. The findings could also have important ramifications for research in other areas—notably, cancer—where the same kinds of cells play a major role.
Until now, scientists thought that epithelial cells—which line the lung’s airways as well as major cavities of the body and most organs—just sat there motionless like tiles covering the floor, or like cars jammed in traffic, said Jeffrey Fredberg, professor of bioengineering and physiology at Harvard T.H. Chan School of Public Health and one of the senior authors of the study, which was published online August 3, 2015 in Nature Materials. But the study showed that, in asthma, the opposite is true.
The physics of biology
The researchers decided to look at the detailed shape and movement of cells from the asthmatic airway because, according to Fredberg, a growing body of research is showing that physical forces change how cells form, grow, and behave. Given this knowledge—and the fact that no one knows what causes asthma, which afflicts more than 300 million people worldwide—it made sense to look at the shape and movement of epithelial cells, which many scientists think play a key role in the disease.
The study included lead authors Jin-Ah Park and Jae Hun Kim, research scientists in the Department of Environmental Health who study asthma, and Jeffrey M. Drazen, a pulmonologist and professor in the Department of Environmental Health, who studies “mechanotransduction” in asthma—how the bronchial constriction of asthma might trigger cell changes in the epithelium. The study also included mathematical physicists James Butler, senior lecturer on physiology in the Department of Environmental Health, and M. Lisa Manning and Max Bi at Syracuse University, as well as other colleagues from Harvard Chan School and other Harvard institutions.
To analyze cell movement, the researchers took time-lapse images of epithelial cells. They also produced videos that show quite vividly the differences between normal cells and asthmatic cells. The videos, shown above, show that the normal cells are nearly pentagon-shaped and are jammed—they hardly move at all—while the asthmatic cells become more spindle shaped and are unjammed—they constantly move and swirl.
To analyze the mechanical forces at work, the researchers placed layers of epithelial cells—either from normal airways or asthmatic airways—on a soft gel surface that simulates the degree of stiffness of the lung. As the cells moved, their push-pull motion caused movement in the gel as well. This gel movement then enabled the researchers to infer the mechanical forces at work among the cells.
Now that it’s known that epithelial cells in asthmatic airways are oddly shaped and are not jammed, scientists have to figure out why it’s happening—whether it’s asthma causing the cells to unjam, or if it’s the unjamming of these cells that causes asthma.
“It’s a very big question to figure out why this particular cell shape and movement is happening,” said Park. “We know that asthma is related to genes, environment, and the interaction between the two, but asthma remains poorly understood.”
Whatever the reason, knowing more about how these cells jam and unjam is important, said Fredberg, because epithelial cells play a prominent role not just in asthma, but in all processes involving cell growth and movement—including organ development, wound healing, and, importantly, cancer. The new findings about epithelial cells open the door to new possibilities for developing drugs to fight asthma as well as other diseases—and to new research questions.
“Trying to define how cells behave, how they exert forces on each other, and how that changes what they do are big open questions,” said Fredberg. “Researchers all over the world are looking more and more at these questions. It’s very exciting.”
— images courtesy Jeffrey Fredberg and Jin-Ah Park
For original article please click here.
Sepsis kills more than 500,000 Americans each year, but in some ways it remains a mystery to both researchers and doctors. Lester Kobzik, professor in the Department of Environmental Health, and Rose Filoramo PhD ’17 are working together to unravel this medical mystery. (One-on-One podcast series, 7:28)
Pedro Alberto Lamothe Molina, a BPH student in the laboratory of Dr. Bruce Walker, was selected as one of HHMI’s International Student Research Fellows. This program supports international students during their third to fifth years of graduate school in the United States, with awardees receiving $43,000 during each year of the fellowship.
To read more about the HHMI fellowship and this year’s recipients, click here.
In December 1974, the last cases of smallpox in its deadliest form were confined to a Bangladesh slum. Public health workers were preparing the scourge’s coup de grâce, but were horrified when government bulldozers arrived, scattering 50,000 people across the countryside.
The ill-timed demolition of the slum spread the disease throughout the country, sparking outbreaks in several locations and extending the suffering and death from smallpox for another 10 months. The chapter illustrates the difficulty of ridding the world of a human disease, even one down to its last few cases, and how important it is that eradication efforts include whole societies.
A group of scientists, government officials, nonprofit leaders, malaria-control program directors, and others gathered at Harvard Business School last week sought to draw lessons from past eradication efforts as they embarked on a weeklong leadership program focused on eradicating another age-old scourge: malaria.
Though the program’s 56 participants have been involved in different aspects of the fight against malaria for years, Dyann Wirth, the Richard Pearson Strong Professor of Infectious Disease, chair of the Harvard T.H. Chan School of Public Health’s Department of Immunology and Infectious Diseases, and director of the Harvard Malaria Initiative, said that shifting officials’ focus from control and treatment of the disease to eradication requires shifting strategies as well.
“We want to give them the overview of the problem of malaria, all the way from the genes to the globe,” Wirth said. “Many of them work [on malaria]… and although most in the room probably have had this material at one point, they haven’t thought about it in this lens of elimination/eradication, which is quite different from treating symptomatic cases or preventing symptomatic cases.”
Smallpox stands as the only human disease successfully stamped out, so the intensive leadership program kicked off with a talk by Myron Levine, a University of Maryland professor who was a World Health Organization (WHO) consultant in Bangladesh during the final days battling smallpox’s most virulent strain, variola major. It would take another two years to eradicate a less deadly strain, variola minor, though there were laboratory-related cases in 1978.
Global anti-malaria efforts have made significant progress, Wirth said, with cases down 30 percent and deaths down 50 percent over the last 15 years. Even with that decline, however, malaria is far from on the ropes. In 2013 alone, there were an estimated 198,000,000 cases and 584,000 deaths, according to the WHO.
The leadership development program, called “Science of Eradication: Malaria 2015,” provided a broad overview, including the disease’s basic biology, challenges facing vaccine development, social determinants of transmission, economic advantages to eradication, the importance of communication, and ways to integrate eradication into existing control efforts.
The program is a partnership of organizations including Harvard, the Barcelona Institute for Global Health, and the Swiss Tropical and Public Health Institute, with funding from several other organizations.
Malaria may not become the second human disease to be wiped out. That’s because efforts targeting two other ailments, polio and guinea worm disease (which is caused by a tropical parasite), are on the verge of success, with the number of cases reduced to just a handful.
Elizabeth Juma, a research scientist with the Kenya Medical Research Institute, said malaria remains a major health problem there and is the biggest cause of death for children under 5. It’s widespread in the nation’s agricultural areas, making it an issue in agricultural production. Juma said she decided to attend the session to understand how the goal of elimination in Kenya would affect ongoing control efforts.
“The global goals have changed,” Juma said. “We now have to think of malaria elimination. [I decided to attend] to just find out … what should we do about a country such as ours, where this has been attempted in the past, and how best can we think about the endgame, which is elimination.”
Ndukwe Ukoha, a malaria specialist for the Health and Strategy Delivery Foundation, a Nigerian nonprofit that provides technical assistance to the government on health issues, said malaria is also a major public health concern in Nigeria. As Africa’s most populous country, with 184 million people, efforts to reduce malaria there will have an impact on the global disease burden, Ukoha said.
“We are presently controlling malaria in Nigeria, [but] we also need to look at new ways of doing things, new ways of developing more effective tools, because … presently there are issues around resistance and also health system issues,” Ukoha said. “So this kind of forum provides an avenue to talk about these, and even learn from countries where they have successfully achieved high success.”
By Alvin Powell, Harvard Staff Writer
To see original article click here