Alberto Ascherio began his career as a young doctor treating tropical diseases in South American rainforests and parts of Africa. Over the next quarter-century, he made his way to what is now his wheelhouse: studying the links between viruses and neurodegenerative diseases.
Perhaps none of his projects have generated as much attention as his 2022 paper, which offered strong evidence, through a 20-year study of more than 10 million people, that infection with the Epstein-Barr virus, most commonly known for causing mononucleosis, increased the likelihood of developing multiple sclerosis by more than 32-fold. That finding, which happened to come out during the Covid pandemic, has since driven renewed research and investment in both multiple sclerosis and efforts to develop a vaccine against Epstein-Barr, and added to a wave of research on the viral roots of various chronic diseases.
A professor of medicine at Harvard Medical School and professor of epidemiology and nutrition at Harvard’s T.H. Chan School of Public Health, Ascherio is also principal investigator on nearly a half-dozen studies of various diseases, including Parkinson’s and amyotrophic lateral sclerosis. Three are National Institutes of Health-funded studies, and two more are funded by the Department of Defense.
STAT spoke with Ascherio, one of 46 individuals selected for this year’s second annual STATUS List, about his breakthrough finding, his latest projects, and what he hopes to achieve in the next stage of his career. This interview has been edited for clarity and brevity.
Your January 2022 Science paper has over 315,000 impressions, and is considered by some to be one of the biggest medical science discoveries of the past year. What was it like to get that much attention?
It was good, after you work on something for so long. I’m more focused on the science and the next steps. But I realized that the recognition is useful because it generated not just the number of citations, but people now are working on it.
That is what matters to me — that they are trying to find a way to build on this finding, to find a way to prevent or to treat MS. I think it’s been good to shake the field a bit and to attract resources to this area.
Has the recognition helped you get more resources for this work?
I was hoping so but in fact, just three days ago, a study section at NIH reviewed our grant proposal to expand the research in this area and it was disapproved. I wasn’t there, I don’t know why. … We’ve done the big hit and now we need to dig more in depth. And so maybe it did not sound like another breakthrough in six months.
How do you feel about that?
I’m definitely disappointed. I was really counting on this. I thought that we have proven that we can do a useful and important job. But if you look at history, it happens to everyone. Several people who got the Nobel Prize, their grants were rejected repeatedly.
What new opportunities have come up for you since last year? I saw that you’re a principal investigator on five different projects right now.
We do a lot of work. We are sometimes spread even too thin. All around the world there are now groups, opportunities for others at this time, more than for myself. And I’m happy … it cannot be a one-person thing. Several major drug companies have really reshaped their research agenda and they are focusing resources now in this area. Governments are putting grants into this area. I heard Australia has set several million dollars focused on EBV and MS.
“The dream of my life is to do something useful for people with ALS, which is such a dramatic disease.”
Alberto Ascherio, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health
Your study on EBV and MS was a long project. Was there a moment that stands out in your memory, when you realized the work would make a big splash?
Sometimes, where you publish could be at least as important as what you publish. So the big thing has been, obviously, being accepted in Science. It was not a sudden discovery, because during these 20 years we’d been accumulating evidence. It wouldn’t make a good movie, a wow moment that you look at the data and say, ‘Oh, wow! We discovered EBV is causing MS!’
What other conditions other than MS could the Department of Defense serum repository (used to study links between EBV and MS) be used to interrogate?
We have a grant to look at infections in ALS. That has been an exciting project. We submitted a proposal to look at viral infections in Alzheimer’s.
There is a huge potential, if it was possible to link the Department of Defense data with the Veterans Administration data. And we’ve been trying to work on that for at least one year, without much success so far. That would create a really huge potential to discover the causes of Alzheimer’s and other neurodegenerative diseases. That would be, really, the Holy Grail — resources that nobody else in the world has and nobody will ever have.
What are some of the obstacles to doing that?
To do this research in the most rigorous manner, you would need to include all of the people who develop the disease. Ideally, you would have to do this without getting individual consent. Because if you require individual consent, that selects the people who you can reach — they have to be alive, they have to be either mentally competent or have a guardian that can provide it.
“Unless the president of the United States would declare Alzheimer’s a national emergency … that, I’ve been told, is the only way this could be done.”
Alberto Ascherio, professor of epidemiology and nutrition, Harvard T. H. Chan School of Public Health
The privacy laws in the U.S. don’t permit this type of research, even if the data would be entirely anonymous. So unless the president of the United States would declare Alzheimer’s a national emergency … that, I’ve been told, is the only way this could be done.
Are you trying to get the president to declare Alzheimer’s a national emergency?
I don’t, unfortunately, have access at that level. I’ve been discussing it with the Veterans Administration. Indirectly, someone else will have to. Maybe the Alzheimer’s Association, people who have more influence than myself. We are just a small research group. We don’t fly that high.
Can you give us an update on the MS vaccine efforts and some of the challenges involved in that?
From what I understand, Moderna is working on an mRNA vaccine, still in Phase 1, meaning it’s still pretty early. NIH [and] National Institute of [Allergy and] Infectious Diseases has been working for some time on a vaccine. I think GlaxoSmithKline [GSK] worked on a vaccine years ago and now they are refreshing, revisiting it. So there are at least three, and there may be more.
One of the problems is that, if we are talking about a vaccine that prevents EBV infection, it takes several years before it can be proven that it prevents MS. There are vaccines that can be given to people who are already infected just to modify the immune response and prevent reactivation. And even — still very speculative — you could give a vaccine to people who have MS. In theory, it’s a sort of immunotherapy, in which you modify the immune response to the virus in a way that will benefit the disease. But whether that will be possible or not remains to be proven.
Scientific discoveries like yours can hold a lot of promise, but also be frustrating for the average person with MS, because it won’t make much of an immediate difference. What do you tell those people?
I was surprised that people with MS were thrilled to know that we found the cause, even if I made clear: “Sorry, we don’t have a treatment.” They like to know that progress is being made in identifying the cause, even if this doesn’t translate.
In an alternate universe, what might your career have been?
When I finished medical school, I went to work mostly in developing countries, in the forests of Central America, in Africa, to practice medicine and then public health. I would have gone back, probably to work in international health in a developing country. I did love it. The clinical work, in some ways, is more rewarding because you get a person who is sick and if you do a good job, the person will get better.
In research, you need to be very self-motivated because you can do work for years without having any certainty that your work is going to be useful for people. You really need to believe in what you’re doing.
I have one last question for you: What is the number one, most burning question you hope to answer in the next phase of your career?
The dream of my life is to do something useful for people with ALS, which is such a dramatic disease. It’s less common, to some extent, than MS. But the disease course is a relatively rapid progressive disease. The median survival is only about three years. We are working on ALS, and we have some good preliminary results and some clues. That is my dream.
