Curtis Huttenhower, associate professor of computational biology and bioinformatics, has been named winner of the 2015 Overton Prize from the International Society for Computational Biology. The prize recognizes early or mid-career scientists who are emerging leaders in computational biology and bioinformatics for their accomplishments in research, education, and service.
Huttenhower was chosen for his groundbreaking research on microbial communities, with a focus on the human microbiome. He has worked on developing novel computational tools to analyze the large, complex datasets associated with microbial communities and on the National Institutes of Health Microbiome Project. His research has provided new insights into how microbial communities impact human health and disease.
Huttenhower’s research potential has previously been recognized through two other awards: the Presidential Early Career Award for Scientists and Engineers, and a National Science Foundation Career Award.
The measles outbreak that began in Disneyland in December has continued to spread, infecting 102 people in 14 states during January, according to the Centers for Disease Control and Prevention (CDC).
Why is an illness of our grandparents’ generation suddenly resurgent? Are we on the verge of a measles epidemic? Is the disease here to stay? To find out, the Gazette spoke with Dyann Wirth, the Richard Pearson Strong Professor of Infectious Diseases and chair of the Harvard T.H. Chan School of Public Health’s Department of Immunology and Infectious Diseases.
GAZETTE: The CDC’s most recent figure was 102 people infected with measles in 14 states. What’s going on? Isn’t measles something we used to worry about?
WIRTH: It’s one of the vaccine success stories. It used to be that children commonly got infectious diseases such as measles, and then recovered and had lifelong immunity. Since the 1960s, we’ve had an effective measles vaccine — a very good vaccine with long-lasting immunity — and, if vaccinated, the vast, vast majority of people develop lifelong immunity.
What’s going on is there are susceptible people who have not been vaccinated who have been exposed to measles, which is a highly contagious disease.
The current outbreak can be traced to a single individual in California visiting Disneyland. Although measles was eliminated in the United States, there are still countries in the world where measles exists, so importation of measles probably happens quite frequently. But if the individuals exposed are vaccinated, then you don’t have any infection.
GAZETTE: So in the past, folks who have had it and come to the U.S. have run into people who have been immunized so it hasn’t spread anywhere, whereas in this case they ran in to people who hadn’t been?
WIRTH: Yes, that’s right. There’s a concept of herd immunity: If the vast majority of people are vaccinated from a disease or immune from a disease, then even if a disease is introduced into the community it can’t spread because there’s a very low chance that the virus will enter a susceptible individual. But the more susceptible individuals in a population, the larger the chances an infected person will come in contact with a susceptible person, and that’s how the disease spreads.
And it’s highly contagious, so if you’re not immune, then you have a high likelihood that you’ll come down with the disease if you come into contact with it.
GAZETTE: Is it contagious through the air?
WIRTH: Right. There is aerosol transmission of measles. It can linger in a room after the sick person has left, and it has a long incubation period — seven to 21 days after exposure — in which sick people may not have symptoms, which can exacerbate its spread.
GAZETTE: How dangerous is it?
WIRTH: It can have serious complications. It makes people very sick. It’s a very unpleasant disease with a high fever and potential neurological problems that can have lifelong effects.
GAZETTE: Is it potentially deadly?
WIRTH: There is mortality due to measles. It’s not the same kind of mortality you see with Ebola. I would guess most people in this country over 55 or 60 had measles and there’s a very high survival rate, but there are complications that occur at a low frequency compared to something like Ebola, and fatalities at an even lower frequency.
GAZETTE: We’ve been hearing about the anti-vaccination movement. Is it your sense that this is essentially what this outbreak is from, or is there some other dynamic going on?
WIRTH: I think it would be inappropriate to attribute it to the anti-vaccination movement. But it’s important to realize that most people, including the parents of today’s young children, haven’t known anyone who’s had measles. So the threat seems removed and therefore the incentive to vaccinate against a disease that you’ve never experienced yourself and probably no one in your community has experienced is less.
And there were reports — although scientifically without support and eventually retracted — of an association of childhood vaccination with autism. This report has been refuted, retracted, and an Institute of Medicine study looking for any data to support that association came out with there being no basis. Yet this perception still exists and affects the decision of some people about whether they vaccinate their children. Vaccination, of course, is done before children themselves are able to make the decision. This is a decision of parents.
GAZETTE: It seems the anti-vaccination movement is made up of people who intentionally decide that they don’t want this for themselves and their children, but often failures of health care are related to poverty, lack of knowledge …
WIRTH: And lack of access, right.
GAZETTE: Is there some of that going here as well?
WIRTH: In the U.S., measles childhood vaccination is required for enrollment into school. In most states, probably all states, it’s given free by the state public health service. By the time of school enrollment, vaccination is a requirement. You need a religious or philosophical exemption to have your unvaccinated child go to public school.
GAZETTE: Do you have a sense whether this outbreak is a blip, or is measles here in the U.S. to stay?
WIRTH: From what I understand, the vaccination rate is still very high, so I would anticipate that this is not going to continue.
According to the CDC, in 2013, there were 11 outbreaks, three of which were more than 20 cases, including one outbreak with 58 cases. In 2014, there were 23 measles outbreaks, including one outbreak of 383 cases in an unvaccinated Amish community in Ohio.
Measles is contagious before the individual is symptomatic and therefore transmission can occur before an individual is recognized and quarantined. So the more unvaccinated and unquarantined people that come in contact with the virus, the more you will see this rise, but I don’t expect it to stay in most communities. If there is a situation where a significant proportion of an individual community is unvaccinated, as with the Amish in Ohio, you might see something similar to what was seen in 2014.
GAZETTE: When you see a spike within a community, does it — in a way — take care of itself because all those people are now immune?
WIRTH: All those people who survived are immune. When I was a child, I had chicken pox and measles and I’m now immune. Of course, in this day and age, getting immunity that way would cause an unnecessary amount of pain and suffering to your child, especially since we have effective vaccines.
GAZETTE: With regard to people who choose not to vaccinate their children, are we victims of our own success?
WIRTH: Where the threat of the disease is so low that people no longer remember anyone having it, if they think there’s any risk of other complications, you can imagine someone making that decision.
So diseases that have largely disappeared — diphtheria, with very high long-term morbidity and mortality; whooping cough [pertussis], with very dramatic pathology — are also diseases where people don’t get vaccinated.
As someone who spends my life trying to develop cures for diseases for which there are no vaccines and, in many cases, no effective drugs, I find this incredibly frustrating. Here you have a safe, effective, inexpensive, readily usable, life-saving tool that gives you lifelong protection and people choose not to use it. I find it mind-boggling, but it’s very clear that that is what’s going on.
GAZETTE: What is the one thing that the public should know about this?
WIRTH: This is a very contagious and potentially dangerous disease, and if you haven’t been vaccinated or you feel your immunity is waning, you should get vaccinated. That is how to prevent yourself and your children from getting measles.
If you contrast this to the situation with Ebola, no one is panicking that there’s measles in the United States. There’s not that same kind of fear, but there is a simple, cheap thing you can do to completely protect yourself. And yet, somehow, decisions are being made not to do this.
I think demonizing those who don’t vaccinate their children is going to drive them further away. They already have a distrust of the medical establishment. But somehow there needs to be some leadership at the community level. I’m not sure exactly how; maybe the families who’ve been exposed to measles should give testimony about how miserable it is.
I also think there’s a somewhat U.S.-centric view, but Disneyland and other places get visitors from all over the world. Other countries do not have the same level of control, don’t have universal vaccination as we do. So there’s risk, even if you don’t leave the borders of the United States.
And, according to the CDC, the vast number of people who get measles were unvaccinated. There is the occasional person who is vaccinated and doesn’t develop immunity because of a feature of their immune response, but that’s not something you can predict.
By Alvin Powell, Harvard Staff Writer
Anthony Covarrubias, PhD ’15, grew up in a working-class neighborhood in South Los Angeles. While celebrities in sports cars whizzed to the beach just a few miles away, Covarrubias’s neighbors waited in long lines at the local health clinic for low-quality care they couldn’t afford. Although his parents worked hard to make ends meet, access to health care and health benefits was not always available. Acutely aware of this disparity from a young age, Covarrubias decided to get an education and help correct the injustice.
For this Harvard T.H. Chan School of Public Health doctoral student, now in his final year in the Biological Sciences program, the quest to cure metabolic diseases is personal. He’s seen family members and neighbors suffer from diabetes and recently learned of a graduate from his high school who died young from atherosclerosis. Finding a cure for conditions that disproportionately shorten the lives of the poor and people of color won’t be easy, but Covarrubias is in it for the long haul.
“Science teaches you to be patient and persevere,” he says. “Sometimes experiments don’t work out. Sometimes we give it our best effort and it’s still not enough. But that’s what I have signed up for.”
Convinced of the power of science
Covarrubias brings a conviction in the power of science to explain the world and make it a better place, as well as an acute awareness of how the pathways in life—as well as in biology—can change.
On a typical day he pulls out a bottle of blue liquid and portions it into a plastic tray indented like an egg carton. In the tray are macrophages—crucial immune system cells. He slides it into a gene sequencing machine and leans in close to the monitor, brow furrowed. Maybe this time the bar graphs filling the screen will unlock the mysteries of his lab-grown samples—and point the way to a cure for diabetes.
Macrophages are frontline troops in the war against infections, surrounding and digesting bacteria and other cellular invaders and secreting chemicals that launch the process of inflammation. In many overweight and obese people, however, macrophages set off a state of chronic inflammation that can usher in a host of metabolic woes, such as diabetes and atherosclerosis.
Yet just as macrophages trigger inflammation, they also can shut it down. And locating the switch that determines whether the cells’ inflammatory or anti-inflammatory pathway is activated could have lifesaving consequences for millions of people.
That’s what Covarrubias hopes to find and learn how to control. “The best part of being a molecular biologist is that we can think of crazy ideas and actually try them,” he says. “Every now and then, one of them works—and that’s what drives me.” One of his most important findings, which linked a protein in a genetically engineered mouse to macrophage activation, was published this past November in Nature Communications.
Lessons from Skid Row
Covarrubias’s family wasn’t poor, but he grew up surrounded by poverty and saw clearly from a young age the ways it can stunt the health and potential of those it touches. Many of his friends dropped out of high school, got hooked on drugs, and joined gangs.
Visiting Los Angeles’s Skid Row as a high school volunteer, he was drawn to talk to the people who call the five-block district of makeshift shelters home. “A lot of them were just like you and me, at one time,” he says. “They had jobs and families who cared about them. But then something happened, like a divorce, a death, or onset of mental illness, which made them lose control of their lives. With some assistance, many of them could get back on track.”
His focus returned to Skid Row as an undergraduate researcher at the University of California, Los Angeles (UCLA), assisting in the data analysis of a health care intervention for drug addicts in the neighborhood. Though he had once considered becoming a doctor to help improve health in his community, the experience introduced him to public health as an avenue for using his passion for science to help improve people’s lives. Here was a way to delve into the causes of disease at their most fundamental level.
Support and healthy competition
UCLA was also an eye-opener in other ways. Even coming from a respected Catholic high school, Covarrubias was behind his more privileged college classmates—including his film-major roommate—in science classes. But he persevered, and eventually formed a study group with other students of color who helped each other succeed. “We realized that together, we had so much more brain power,” he says. The group became a source both of support and of healthy competition. “We always tried to outdo each other,” says Covarrubias. “You’d see your friend get a 97, so you wanted to get a 98.”
At Harvard Chan, Covarrubias helped launch a similar support group for students in his program. The Biological Sciences data club meets regularly to talk about highs and lows of members’ individual research efforts in a social, pressure-free environment. “You could be working in the lab next door to another student and see them every day, but still have no clue what they are doing,” says Covarrubias.
His recent findings on the link between metabolism and macrophage activation have opened a new research direction in the lab of Tiffany Horng, his adviser. “It would not have been possible without him,” says Horng, assistant professor of genetics and complex diseases, adding that her lab has also benefited from Covarrubias’ “infectious enthusiasm.”
In Horng, Covarrubias has a mentor who won’t settle for less than the best. He tries to be as encouraging with the students he’s mentored over the years, including those in the Biological Sciences in Public Health Summer Research Program for minority undergraduates.
Covarrubias hopes to someday lead an academic research lab. He’s undaunted by statistics on the glut of graduates competing for dwindling tenure-track positions. “I’m not scared by numbers that say only 30 percent of us will get academic jobs,” he says. “Compared to where I started out, those are really good odds.”
— Amy Roeder is assistant editor of Harvard Public Health
Photo: Kent Dayton/ Harvard Chan
There is an arsenal of cost-effective tools available to combat malaria but getting people to adhere to treatment regimens can be challenging, said Jessica Cohen, assistant professor of global health, at a symposium focused on “The Last Mile to Malaria Eradication,” held December 4, 2014 in Kresge G3. It was sponsored by the Department of Immunology and Infectious Diseases and the Harvard Institute for Global Health and included a poster session and reception in the FXB Atrium.
This was the second such event sponsored by the cross-Harvard initiative Defeating Malaria: From the Genes to the Globe. This effort brings together experts from different disciplines within the University to address complex issues related to eradicating malaria. Dyann Wirth, who heads the Harvard Malaria Initiative and is also Richard Pearson Strong Professor and chair, Department of Immunology and Infectious Diseases, called the Defeating Malaria initiative “a transformational way to focus on major public health problems.”
Cohen discussed the challenges of increasing use of bed nets, which provide protection for people while they sleep against malaria-carrying mosquitos. Some people don’t use them properly; others don’t use them at all and subject themselves to hungry mosquitos looking for a blood meal.
She also noted the challenge of getting patients to finish all of their malaria medication. Often they stop taking it because they think that when they start feeling better that they are cured, or if they continue to feel sick during treatment, they blame the medicine and stop taking it. Others may decide to save pills for later for themselves or other family members.
When people don’t finish their medication, they can have lingering parasites. This can lead to reccurrence of the malaria infection and can accelerate the emergence of resistance (i.e. the parasite becoming resistant to the medication). “This is dangerous because we don’t have any other very effective malaria medications available if the current one fails,” she said.
In a test group in Africa, Cohen and her colleagues found when they experimented with adding simple stickers to bottles of medication that read “Malaria is not gone until all tablets are finished,” that compliance to the regimen increased about 7%. They also are experimenting to see if more attractive and simplified medication packaging will help.
According to the World Health Organization’s World Malaria Report for 2014 released on December 9, 2014, 3.2 billion people in 97 countries and territories are at risk of being infected with malaria. In 2013, there were an estimated 198 million malaria cases worldwide and an estimated 584,000 deaths. Ninety percent of the deaths occurred in Africa. The disease killed an estimated 453,000 children under five years of age.
“We’ve made tremendous progress over the last 50 years thanks to the global investment that has led to a remarkable scale up of key interventions, but we’re not anywhere close to the last mile in many countries,” said speaker Günther Fink, associate professor of international health economics. Over the last 150 years, about half the world’s countries have eliminated malaria, he said. “Fifty percent of the world lives malaria-free, but this means 50% of the world still has malaria. We need new tools and we need to move fast.”
While global incidence of malaria is down, in parts of Africa it’s up, said Barry Bloom, Harvard University Distinguished Service Professor and Joan L. and Julius H. Jacobson Professor of Public Health. Fifty-nine countries are expected to meet the United Nations’ malaria reduction targets by 2015 and more than 50 will exceed the targets. “Only 18 countries are responsible for 80% of the cases,” he said. Most deaths from malaria occur in the Democratic Republic of the Congo and Nigeria.
Matthias Marti, associate professor of immunology and infectious diseases, co-hosted the symposium and Michael Reich, Taro Takemi Professor of International Health Policy, was a moderator. Other speakers included Caroline Buckee, assistant professor of epidemiology; Marcia Castro, associate professor of demography; Flaminia Catteruccia, associate professor of immunology and infectious diseases; Manoj Duraisingh, professor of immunology and infectious diseases, and Sarah Volkman, principal research scientist.
– Marge Dwyer
photos: Craig LaPlante
November 3, 2014 — Cutting-edge work on homeostatic regulation—the process through which the human body maintains stability in response to changes in external conditions—was the focus at the 17th annual John B. Little Symposium, held October 24-25, 2014 at Harvard School of Public Health (HSPH).
About 180 attendees heard from numerous experts in the field, who discussed topics ranging from radiation epidemiology to fat synthesis and storage to how certain genes and small molecules extend lifespan. HSPH faculty presenters at the symposium included Robert Farese, professor of genetics and complex diseases, and Gökhan Hotamisligil, chair of the Department of Genetics and Complex Diseases.
The John B. Little Symposium is hosted each year by the John B. Little (JBL) Center for Radiation Sciences and Environmental Health. Both the symposium and the center are named for John B. Little, James Steven Simmons Professor of Radiobiology Emeritus, one of the first scholars to characterize problems in public health as interactions between environmental stressors and humans’ response to those stressors.
In his introduction to the symposium, Hotamisligil praised Little as the “inspirational leader in our department, and father of this field, and father of the symposium.” Little was on hand to welcome attendees.
Both Hotamisligil and Dean for Academic Affairs David Hunter, who gave opening remarks, also acknowledged the support of alumnus Gerald Chan, SM ’75, SD ’79, a former student of Little’s and a director of the Morningside Foundation. The Foundation and Dr. Chan have provided crucial support for the JBL center and the symposium. They also supported the establishment in 2012 of the Morningside Professorship in Radiobiology, in honor of Little. In September of this year, the Morningside Foundation and the Chan family gave HSPH a transformational gift of $350 million in unrestricted endowment—the largest single donation in Harvard’s history and, according to Hunter, the 6th largest to any university in the world. In acknowledgement of the gift, the School will be renamed the Harvard T.H. Chan School of Public Health, in honor of Gerald Chan’s father.
Hunter also announced that the JBL Center will become a school-wide collaboration among the Department of Genetics and Complex Diseases (its current home), the Department of Environmental Health, and the Department of Epidemiology. Hunter said the move is being made possible by a generous gift from an international donor.
This year’s symposium was organized by Zhi-Min Yuan, professor of radiobiology and director of the JBL Center; James Mitchell, associate professor of genetics and complex diseases; and Brendan Manning, professor of genetics and complex diseases.
photos: Tony Rinaldo
Harvard University will announce today a $350 million gift — the largest in Harvard’s history — to support efforts at the School of Public Health(HSPH) to tackle the world’s toughest health challenges.
The gift comes from Newton, Mass.-based The Morningside Foundation, established by the family of the late T.H. Chan, which has focused its philanthropy primarily on education, health, and faith-based organizations in North America and Asia. The gift will also lead to the renaming of the School, which will be called the Harvard T.H. Chan School of Public Health.
Harvard School of Public Health Dean Julio Frenk said the gift will focus on four global health threats: pandemics old and new, such as malaria, Ebola, cancer, and obesity; harmful physical and social environments such as those resulting from tobacco use, gun violence, and pollution; poverty and humanitarian crises such as those stemming from war and natural disasters; and failing health care systems around the world.
“The Chan family’s commitment to education and their belief in the power of public health is an inspiration, and their generosity will ensure we have the resources to continue to develop the most innovative solutions that will enable millions of people to live longer and healthier lives, now and in the future,” Frenk said.
Harvard President Drew Faust said the gift signals that this is a “public health moment,” a time of action and opportunity to improve people’s health and lives around the world.
“The field of public health drives discoveries that lead to healthier, longer, more-productive lives,” Faust said. “This extraordinary gift from the Chan family will enable Harvard’s School of Public Health to tackle intractable health problems and to translate rigorous research into action and policy worldwide. The Chan family’s generosity sends a signal to the world: This is the public health moment. We are honored by this gift. It will inspire a new generation of public health leaders.”
The $350 million gift will be formally announced during an event live-streamed from the School today at 12:30 p.m. The donation comes as part of The Harvard Campaign, a seven-year, $6.5 billion fundraising effort that kicked off its public phase a year ago and which by the end of May had raised more than $3.8 billion from more than 100,000 donors.
Gerald Chan, a director of The Morningside Foundation who received master’s and doctorate degrees from HSPH in the 1970s, said his father was a “staunch supporter of education” and would be pleased with the gift.
“On behalf of my mother and my brothers, I want to express how pleased we are that the legacy of our late father can be honored by this gift to HSPH,” Chan said. “He was a generous man who was a staunch supporter of education. He also wanted to support scientific research to alleviate human suffering. He would be very pleased with this gift today and all the good works that this gift will enable.”
The gift, which will be added to the School’s endowment funds, is the second The Morningside Foundation has given to the School. In 2012 it endowed a professorship in radiobiology.
Meredith Rosenthal, professor of health economics and policy and the School’s associate dean for diversity, said the gift is “unprecedented” in size and can transform what the School does, how faculty and students work, as well as allow HSPH to bring in a more diverse population of faculty and students.
Rosenthal said that increasing diversity has always been a priority at the School, but the gift could allow HSPH to increase support for qualified students from lower socioeconomic backgrounds and from developing nations. Such support, she said, would allow such students to graduate from HSPH and return home to work free of the burden of loans.
Another possible impact would be to lessen dependence on government research grants that finance much of the work at HSPH. Though grants allow research to move forward, they also keep faculty members focused tightly on specific work, Rosenthal said. Additional funding, she said, could enable more collaboration across disciplines, potentially fostering new approaches and problem-solving.
However it is used, Rosenthal said she believes the gift represents the donor’s commitment, not just to HSPH, but to the importance of improving health around the world.
“This gift is really a commitment to population health on a global scale,” Rosenthal said. “We are incredibly privileged at the Harvard School of Public Health to get it.”
David Hunter, the Vincent Gregory Professor in Cancer Prevention and the School’s dean for academic affairs, said faculty and students will see changes from the funds in several ways. Not only will the money help hire faculty at the top of their fields and reduce the financial burden on talented but disadvantaged students, it will support changes to the doctoral program and boost a fund to provide initial support for research not ready to qualify for more traditional grant programs.
In his own research field of cancer prevention, Hunter said the gift sends a message that prevention is critical, particularly because the number of people with cancer is expected to double worldwide in the next 25 years. It also provides encouragement to faculty and students that they will have the resources over time to address the daunting, globe-spanning problems on the world’s health agenda, he said.
“Each of these areas represent major, complex problems in the world for which simple solutions are not available,” Hunter said of the School’s four areas of emphasis for the gift. “A gift like this really helps us organize for the long term, but gives us confidence we can make near-term progress … and faculty and students can commit themselves to finding solutions to those problems.”
As academic dean, Hunter said he was particularly gratified that the gift came from an alumnus, illustrating the link between the School, its students, and its alumni community, and linking the past and the future.
The four areas identified by Frenk encompass some of the most pressing challenges the world faces in any field and areas where HSPH faculty members are already at work.
Global pandemics include both old ailments, like malaria, which has been around for millennia and still kills hundreds of thousands annually, and new ones that take their own deadly toll, like AIDS, SARS, and Ebola. It also includes noncommunicable diseases such as cancer, and conditions related to lifestyle, such as obesity and diabetes.
HSPH researchers are already at work in many of those areas: Richard Pearson Strong Professor of Infectious Diseases Dyann Wirth focuses on malaria, heading the Harvard Malaria Initiative, while Mary Woodard Lasker Professor of Health Sciences Max Essex’s contributions to fighting AIDS continue to mount through the Harvard School of Public Health AIDS Initiative he heads and its Botswana-Harvard AIDS Institute Partnership. Fredrick Stare Professor of Epidemiology and Nutrition Walter Willett and data from the long-running Nurses’ Health Study and related surveys, meanwhile, shine a bright light on diet and nutrition.
A second major focus includes ills related to physical and social environments, such as gun violence, tobacco use, and substance abuse, as well as environmental issues such as air and water pollution. Associate Dean Jay Winsten and the Center for Health Communication he directs are following on the dramatic success of the center’s designated driver campaign in the late 1980s and early 1990s. Now it is working to end distracted driving caused by cellphones and other technology in automobiles, which killed 3,328 in 2012 alone, according to the National Highway Traffic Safety Administration.
Failing or nonexistent health care systems are a major source of suffering not just in the U.S., but also around the world, where they mainly affect the global poor, who die from infection, disease, childbirth, and other causes that rarely kill in developed nations. Faculty research seeks to address the problem in a variety of ways, while initiatives such as the Ministerial Leadership in Health Program, a joint program between HSPH and the Harvard Kennedy School led by Executive Director Michael Sinclair, aim to strengthen health care systems by strengthening leaders to better meet the steep challenges they face and expand access and quality of care, both domestically and internationally.
Humanitarian crises, whether from war, natural disaster, or other causes, remain a significant source of human suffering and another key area of emphasis for HSPH moving forward. The Harvard Humanitarian Initiative, headed by Professor of Global Health and Population Michael VanRooyen, and the FXB Center for Health and Human Rights, led by François-Xavier BagnoudProfessor of the Practice of Health and Human Rights Jennifer Leaning, are just two organizations based at the School that foster research and teaching to both improve the response to large-scale humanitarian crises, such as the 2010 Haiti earthquake, and instill the idea of health as a basic human right, applicable to Syrian refugees living in Lebanon, enslaved laborers in factories and fields around the world, and exploited and trafficked women and children.
“The Chan family’s transformational gift will help us empower current and new generations of talented and diverse students and faculty to address the complex health threats challenging the U.S. and the world,” Frenk said.
A live stream of the event will be available online today at approximately 12:30 p.m. EDT.
By Alvin Powell, Harvard Staff Writer
After decades on the front lines of the HIV pandemic, Max Essex has seen his share of both setbacks and victories.
There have been far too many deaths, some among colleagues in Botswana, where the Harvard AIDS researcher does much of his work. There have been frustrating years in the lab searching for a vaccine to master the disease, with nothing so far to show for it in clinics and hospital wards.
But there have also been important successes, such as the research that showed anti-retroviral drugs given to pregnant or breastfeeding women can stop HIV transmission to their babies. Today, that practice can protect more than 98 percent of such babies — better than the best vaccines.
The use of drug treatment to prevent new infections was further validated in research on so-called discordant couples, where just one partner is infected with HIV. Studies, including those conducted in part by Essex and the Harvard School of Public Health AIDS Initiative (HAI), have shown that treating the infected partner with powerful antiretroviral drugs can prevent transmission to the non-infected partner.
Those victories, and similar work by researchers around the world, have fueled the latest attempt to corral HIV. The strategy, called “treatment as prevention,” seeks to apply smaller successes to the whole population, using early, enhanced drug treatment both to treat the sick and to keep the virus at levels low enough to reduce transmission, with the hope of choking off the pandemic.
Treatment as prevention has been gaining sway in the global AIDS community in recent years. In 2011, then-Secretary of State Hillary Clinton hailed it as a possible route to “an AIDS-free generation,” and it was included in the State Department’s 2012 blueprint toward that goal. But whether it can actually work to reduce infection at the community level remains an open question.
Essex, who is the head of HAI and the Mary Woodard Lasker Professor of Health Sciences, has joined with a group of collaborators on a massive trial to test the strategy scientifically. The trial is needed to confirm that a strategy proven successful in smaller, targeted groups will work in the general population. It is also needed to provide the kind of solid scientific footing required to persuade governments to fund a major expansion of drug treatment worldwide.
The Botswana Combination Prevention Project —“Ya Tsie” in Setswana, the country’s dominant language — is an enormous undertaking. It involves partners from HSPH, the Botswana Ministry of Health, the Botswana-Harvard Partnership, and the U.S. Centers for Disease Control and Prevention, and is funded through the U.S. government’s PEPFAR program. After two years of preparation, it is in the process of enrolling more than 100,000 people, age 16 to 64, living in 30 villages across the country.
“It’s a big trial, obviously,” Essex said, “and it’s part of an approach most people recognize as important in the future, using treatment interventions as prevention.”
The trial villages are paired with control villages getting the current standard of care, though with the latest in medical record-keeping and improvements in medical equipment and supplies. The villages where treatment as prevention is being tested will receive a combination of several established strategies that researchers hope will prove more effective together than the sum of their parts. Among the strategies: in-home counseling and testing, mother-to-child interventions, and voluntary circumcision of uninfected men.
The key intervention, however, will provide anti-retroviral drugs according to two measures, rather than just the one used as the current standard. The current standard is a measure of HIV’s destruction of immune cells, called “CD4 counts,” which have become medical shorthand for measuring progression of the disease. Counts below 350 CD4 cells per microliter of blood are a common threshold — and the one used in Botswana — at which anti-retroviral therapy starts.
Essex thinks that if lowering infectivity is a key goal, then the standard should reflect infectivity, not how sick a person is. The best measure of that, he believes, is viral load, which tallies the number of copies of the virus in the bloodstream. That has direct bearing, he said, on how easy it is to infect a sex partner, and can be high even before CD4 counts fall enough to prompt government-funded antiretroviral drug therapy.
“There’s pretty good evidence that viral load is the best correlate of transmission,” Essex said. “People without high viral load don’t transmit.”
Those enrolled in the Ya Tsie trial will begin drug therapy when viral load tops 10,000 copies per milliliter of blood or when their CD4 counts drop below 350 cells per microliter.
“There’s some overlap between CD4 and viral load, but there’s a significant number of people with high viral load but with CD4 even above 500,” Essex said. “We’re targeting people with high viral load but who are above the standard of care.”
Victor De Gruttola, the chairman of HSPH’s Biostatistics Department and the Henry Pickering Walcott Professor of Biostatistics, said faculty and students have devoted years to refining statistical methods to aid in design, monitoring, and analysis of the trial. A key element is genetic tracking of the virus in study participants, which will provide insight about the extent to which viral strains circulate within and across villages, an important consideration in evaluating the success or failure of the intervention.
“What we’d really like to know is what would happen if you rolled out the intervention to an entire sexual network,” De Gruttola said. “What we’re finding out is what actually does happen to HIV incidence in a village receiving the intervention that is surrounded by nonintervention villages. But studying viral genetic linkage provides a basis for estimating what the intervention’s effect would be if all nearby villages received the intervention.”
De Gruttola said that is just one issue that statisticians and others involved in the study design have been considering. Another is the likelihood that participation in the trial won’t be equal — some groups, particularly young men, are more difficult to enroll than others.
Data collection for the trial is expected to last four years, Essex said, followed by about a year of analysis before major findings can be released. Secondary analysis of the data will likely continue for years afterward, he said.
Essex is hopeful that treatment as prevention can provide another tool to fight the AIDS pandemic, which even with significant progress in recent years still has an enormous impact, infecting some 24 percent of adults in Botswana. He is cautious, however, about the chances for a home run against the disease.
Even if the intervention proves effective, it would still have to gain political backing to be included in government health programs, with cost a key factor — another reason Essex has decided to explore viral load as an indicator of when therapy should start, rather than just beginning therapy as soon after infection as possible, as other trials are investigating. Though the latter approach would doubtless have a dramatic effect on the disease’s spread, it would likely also be expensive enough to make rallying the necessary political support difficult. An expansion of treatment to just a subset of the population, one with a high likelihood of infecting others but not yet sick enough to qualify for drug treatment, may be more politically palatable.
“We’ve had unbelievable progress with drugs since the early to mid-’90s, both from the standpoint of saving lives of people who’ve already progressed to disease and preventing mother-to-child transmission,” Essex said. “[But] convincing everyone that they can and should [support a new intervention] from the standpoint of resources, of policy … is never easy.”
By Alvin Powell, Harvard Staff Writer
“Jamie Star challenges and enables us to do something important, without being prescriptive about how it’s done,” Douglas Melton, the Xander University Professor and Thomas Dudley Cabot Professor in the Natural Sciences, said Tuesday about the Star Family Challenge for Promising Scientific Research.
At the inaugural awards ceremony for the challenge, Melton, who chairs the committee behind it, related an important dinner conversation with its founder, James A. Star ’83. Melton said the two discussed the need to fund interdisciplinary research, and the result was a clear target.
“We want to fund research which would not otherwise be funded, research that would be new, and that would have large potential impact,” Melton said. “This kind of research often happens when you look between fields.”
The challenge was established by Star and funded at his direction with a $10 million grant. Given biannually to Harvard faculty members, the awards range from $20,000 to $200,000 and are determined by a committee of senior FAS members.
At the ceremony in a packed University Hall, this year’s four winners presented research with jaw-dropping potential. Charles Lieber, the Mark Hyman Jr. Professor of Chemistry at the School of Engineering and Applied Sciences (SEAS), is researching ways to use nanoscale technology to create electronics that could be injected into the brain and become fully integrated with neural networks. The results could someday be used to treat diseases and traumatic injuries, Lieber said, citing epilepsy and Parkinson’s disease. Such “injectable electronics” would be much less invasive than surgery.
Lieber also described his “ultimate dream”: “injectable closed-loop systems for the detection, monitoring, and treatment of diseases.”
Richard Lee, a professor of stem cell and regenerative biology at Harvard University and professor of medicine at Harvard Medical School, said a simple question lay at the heart of his research: “Can DNA tell time?” He followed with another: “Why is it that a dog keeps track of time seven times longer than we humans do?” The mechanism by which DNA tracks time is “one of the great unsolved mysteries of science,” said Lee, and the answers could help fight disease.
Lee noted that people with muscular dystrophy die at about age 20, and those with cystic fibrosis die at about 30. “We’d like to extend this time,” he said. “Could we slow down time within the muscles of MD patients or within the lungs of CF patients?” He added in a later interview, “I am a physician, so thinking about patients with diseases is all that I do. I dream about being able to slow down diseases, or delay their onset.”
Conor Walsh, an assistant professor of mechanical and biomedical engineering at SEAS, is developing wearable technology — “soft wearable robots” that could someday help people with limited mobility walk with their normal gait. His interdisciplinary research combines robotics, engineering, and biomechanics.
Bernardo Lemos, assistant professor of environmental epigenetics at Harvard School of Public Health, studies the extraordinary resilience of microanimals called tardigrades. “These organisms can be boiled, frozen, desiccated, sent into space, subjected to radiation, and yet still remain alive,” Lemos said. His research has potential in biotechnology, materials science, and public health. “Those of us in public health worry about pollution, lead paint, heavy metals, and how all the toxicity they spread impacts us. Well, tardigrades are barely impacted at all by these things,” and knowing why could advance research, he said.
After hearing from the four winners — selected from more than 60 submissions — Star said, “These were phenomenal presentations. I’m so glad to be supporting such cutting-edge research.”
The challenge will continue to encourage submissions from both the natural and social sciences at Harvard, and work to help close the funding gap faced by researchers.
By Chuck Leddy, Harvard Correspondent
In our video series “Why Public Health?” we ask Harvard School of Public Health students and alumni to talk about what drew them to the field. Anthony Covarrubias, a doctoral student in the Biological Sciences in Public Health program, talks about growing up without health insurance, and his new determination to understand and make an impact on obesity from a molecular level.