Dr. Monto's War on Flu

Dr. Monto's War on Flu

At an age when most professors would be considered tired old war horses, Arnold Monto is a road warrior. From a county health department in Texas, to the vaccine panel advising the Brazilian government, to a closed-door session of the parliamentary leadership of Canada, everyone seems hungry these days to know more about the threat of pandemic influenza. Monto is their go-to guy. He’ll be glad to patiently explain influenza to anyone, even if it means visiting Brazil for less than 24 hours.

His knowledge of this ancient, deadly foe is encyclopedic and personal. He has been watching respiratory viruses, especially flu, warily since the 1960s. Many of the landmark papers in influenza bear his name.

Until a few years ago, nobody seemed to be paying attention, but with the rise of bird flu, they are now. “I think about the plague years,” he says over a glass of wine and his third slice of individually wrapped cheese in the Northwest Airlines lounge at Reagan National Airport. “Airlines will shut down because people will not be willing to go to some places. Since everybody will want to stay home, they’re going to have a lot more delivery pizza—not chicken on a pizza probably—but pizza.”

Monto has just come from a briefing in a Cold War era meeting room at the U.S. State Department where he showed a slide of New York City cops wearing thin cotton masks against the deadly 1918 Spanish flu. “Not a whole lot has changed,” he intoned.

The Experts’ Expert

At age 73, Monto continues to maintain a travel schedule that would punish a man half his age. In April, May, and June of this year, relatively slow months, he hit San Francisco twice, San Juan, Daytona Beach, Atlanta, S8Bo Paulo, Paris, and New York. A trophy in his home near the Arboretum acknowledges more than five million lifetime air miles.

when he does manage to spend time in his School of Public Health office, Monto’s e-mail inbox fills with correspondence from the highest levels of the World Health Organization, the National Institute of Allergy and Infectious Dis-eases, and the Centers for Disease Control and Prevention.

Monto’s stature is singular.

In an age of multidisciplinary research and dozens of co-authors, his name appears alone on last year’s authoritative New England Journal of Medicine perspective about the threat of an avian influenza pandemic, and on a 200-page monograph about influenza for practicing physicians.

“He’s really considered one of the masters in respiratory illnesses,” says Dr. Anthony Fauci, director of the NIAID at the National Institutes of Health. But to laud his longevity or to call him a grand old man would be unfair because Monto continues to be so active and relevant, Fauci adds. “He has doggedly stayed with the issue of respiratory viruses, especially influenza, for many, many years.”

“Arnold knows the literature going back decades,” says Nancy J. Cox, director of the Influenza Division at the CDC. “He often will remind us of studies done decades ago that have data that should put to rest the issues that people are still arguing about!” Cox says.

Cox and Monto serve together on the critically important Vaccine Strain Selection Panel, which must decide in February which three strains should be in the U.S. flu vaccine nine months later. It’s a devilishly difficult choice involving disease surveillance, virology, the practical limits of manufacturing, the vagaries of time and mutation, and a host of other unknowns.

“Arnold understands all of the aspects of the problem, the epidemiology, the virology, the nature of vaccine production,” Cox says. “And he is excellent at asking the right questions.”

Speaking invitations pour in, and reporters call nearly every day. You’d think he’d tire of it, but Monto is a vigorous man. “I like to be home for a while, but I don’t like every day to be the same,” he says with typical understatement. He and Ellyne, his wife of 48 years, have four grown children and ten grandchildren.

A Careful Scientist

Arnold Monto was the first of two children born to a Brooklyn schoolteacher and a general practitioner who’d emigrated to the U.S. from the Baltic states. Having driven a New York City cab to earn his way through medical school, Monto’s father saw patients in the street-level office below their home. His parents hadn’t forgotten the lean years or the value of hard work and an education. “I was encouraged to be interested in the sciences, naturally,” Monto says.

His initial exposure to the research life came through working with hibernating bats as an undergraduate at Cornell. He thought it would be a good path for him, but his parents insisted he get an MD rather than a PhD. “They said it would be like a union card; you can do whatever you want. But I never intended to go out and practice. I was attracted to the ivory tower, which I’ve discovered doesn’t exist.” Or perhaps he just chose not to dwell in it.

After a residency in internal medicine and a fellowship in infectious disease, Monto joined the U.S. Public Health Service to monitor respiratory diseases in Panama. “I learned epidemiology in the field.”

The major draw for Monto to come to Michigan in 1965 was the massive Tecumseh Study, led by the iconic chair of UM epidemiology, Dr. Thomas Francis Jr. Loosely modeled after the landmark Framingham, Massachusetts, heart study, the Tecumseh Study was a large-scale, long-range epidemiological experiment to measure and understand the chronic and acute disease dynamics of an entire village, in real time, with real people. It was hugely ambitious and generously funded. Monto was brought in to study infectious diseases, which had always been Francis’s first love.

Through countless throat swabs and blood draws on ten percent of the village’s population, Monto tracked the arrival and dispersal of all sorts of colds, coughs, sniffles and sore throats in the homes, workplaces, and schools of Tecumseh, assembling what is probably the world’s best type collection of cold-causing rhinoviruses along the way.

Three years after Monto arrived at SPH, Tommy Francis just happened to be in Hong Kong when an aggressive new influenza appeared. Francis, who had developed the first effective influenza vaccine and led the heroic field trial of the Salk polio vaccine, shot a telegram back to SPH faculty member Fred Davenport in Ann Arbor: “MAJOR OUTBREAK OF INFLUENZA. MAY BE NEW VIRUS. ACTION.” Francis was right. This became the last truly pandemic influenza, the “Hong Kong Flu” that killed 33,800 Americans between September 1968 and March 1969.

As the virus began to circle the world in the fall of 1968, Monto was perfectly positioned in Tecumseh to conduct a rigorous, controlled experiment on how to use a vaccine against an ongoing epidemic. “When you’re in preventative pursuits and the thing occurs that you were trying to prevent, you end up studying it.”

It was probably too late to contain the virus to any extent, but Monto wanted to see if he could at least slow it down or prevent deaths. He drove to Indianapolis to personally pick up a batch of scarce vaccine directly from Eli Lilly and Co. and then proceeded to vaccinate 90 percent of Tecumseh’s elementary-aged schoolchildren and 70 percent of the high schoolers. The notion was to create “herd immunity” by vaccinating some important portion of the population to reduce everyone’s risk of infection.

“The concept of herd immunity is hot right now,” NIAID’s Fauci says. “And whenever it’s mentioned, Arnold’s name comes up. Arnold was fascinated by the idea of herd immunity and into it a long time ago.”

When all the data were in the following spring, Tecumseh and its families had clearly suffered far less from the Hong Kong flu than their neighbors in nearby Adrian. “It showed us how much the kids are vectors,” Monto says. “My feeling, from what we saw in Tecumseh, is that you can blunt the impact.”

Though now almost 40 years old, the Tecumseh experiment is still the gold standard for addressing an influenza outbreak. “It is a seminal study that hasn’t been replicated since,” CDC’s Cox says. The pandemic models being used by the WHO and the CDC to anticipate the patterns and potential of a large-scale outbreak are still largely based on Monto’s Tecumseh data.

Monto’s work also is required reading for new officers of the Epidemic Intelli-gence Service at the CDC, some of whom have been pleasantly surprised to find him still helping the agency set infectious disease policy.

As he waits for the pandemic he feels is inevitable—maybe not this year, maybe not next, but some day—Monto has hope: If, in the face of an emerging pandemic, health officials can get treatment to a community’s first cases and apply preventative vaccine to their closest contacts, it may be possible to slow the spread of a virus. But everyone has to be on their toes, carefully watching for cases and responding immediately. “You won’t stop it,” Monto adds. “You’re spreading it out, buying time, reducing the surge, but you’re not going to be able to stop it.” Time is of the essence in an effective response, he explains, because influenza multiplies and sheds for at least a couple of days before the host feels any symptoms. All the while, this “index case” is riding the train, shaking hands, sitting in meetings with coworkers, and kissing the kids before she falls ill, by which time the virus has already quietly taken root in her contacts. And they, in turn, circulate for a couple of days before the fever starts.

Seeing Is Believing

Arnold Monto is a scientist to the core. Conventional wisdom is never enough; he wants to see the data. “I’ve been called a contrarian, yes,” he says, steering a rental car into the swirling traffic around the Jefferson Memorial after his State Department briefing. “Sometimes I tell things the way they are, even if it’s politically incorrect.

“Epidemiology is the science of public health,” he explains. “It’s more scientific and rigorous in terms of its approach.” But in contrast to biostatistics, epidemiology also can be a little messy, a little less cut and dried. “We have to deal with the real world, like legislators and school boards.” An epidemiologist also has to deal with history and experience, notes SPH epidemiology professor Siob87n Harlow, and Monto is a priceless source of both. “When my students are interested in infectious disease, I tell them to just go sit by his side and listen to his stories.” They learn things through his anecdotes that can’t be found in any textbook or class, she says. “You go to him to learn the field—the wisdom of the field and the facts of the field.”

He has shepherded a dozen doctoral students through SPH. “What I most valued as a student was his astute and practical insight,” says John “Chris” Victor, a 2006 PhD who is now a clinical trials advisor to the Japanese Encephalitis Vaccine Program and Rotavirus Vaccine Program for Seattle-based PATH, the Program for Appropriate Technology in Health. “Dr. Monto really helped me to deconstruct the world of international health and to understand the complex organizational (and even personal!) relationships that make international health one of those topics that is virtually unteachable in a traditional classroom.”

Monto’s rank is just professor. Although he once stepped in as an acting department chair, he has never been a chairman, or an associate dean, or an endowed chair. “Deans wind up spending their lives in meetings and I just don’t like being in meetings without a clear goal.”

Rather than resting on his well-deserved laurels, Monto continues to gather important data that will improve our understanding of influenza. His lab is currently in the third year of a large study called Flu-Vacs that is comparing the effectiveness of a traditional killed-virus flu shot to the attenuated-virus nasal spray, FluMist, developed in the laboratory of his colleague Hunein “John” Maassab at SPH.

More than 2,000 healthy adults in Ann Arbor, Livonia, and Mount Pleasant have been given a shot, a nasal spray, or a placebo and then monitored to see whether they become infected and how their antibody levels respond.

But if pandemic influenza takes hold this winter and it’s the Avian H5N1 strain that everyone has been watching, there won’t be enough vaccine, nor even enough needles to administer it, Monto predicts. Antivirals may or may not work, leaving aside the question of whether the drug stockpiles everyone is building can be accessed in time and distributed to the right people.

That leaves non-pharmaceutical approaches like masks and handwashing, avoiding crowds, closing down schools for several weeks, staying home, and ordering pizza. Monto’s gathering data on those ideas too.

“I’m not sure the alcohol hand-washing will do anything more than chap your hands,” he says with rigorous bluntness, because nobody has actually tested hand sanitizer against influenza. To answer some of these questions, he and SPH colleague Allison Aiello are paying some undergraduate students living in dorms to wear masks and wash their hands regularly this fall.

The A(H5N1) avian influenza has been subject to intense surveillance since it was first identified in 1997 and has spread through domestic fowl and migrating birds in much of Asia and Europe, killing 134 humans, two Vietnamese zoo tigers, and at least one German house cat. Though it has killed more than half of its known human victims, H5N1 has yet to make the leap to be highly contagious to humans.

In September, Monto was invited to join the WHO’s ad hoc pandemic influenza task force, a select international team that would convene in Geneva during an emergency and make critical decisions, such as shutting down airports or shifting resources around the world.

Everyone’s on the alert, in part because there hasn’t been a real pandemic since 1968. The “swine flu” of 1976 was a false alarm, egged on initially by the mysterious deaths in Philadelphia of some American Legion conventioneers felled by what turned out to be a novel new respiratory illness. Swine flu only killed one person that we know of.

The latest pandemic scare was SARS, which turned out to be more fearsome in appearance than action. The Severe Acute Respiratory Syndrome, caused by a corona virus, seemed to spread human-to-human with remarkable ease, popping up in Vancouver and Toronto in 2003 just days after its identification in Hong Kong. It had killed a few people and appeared to move through air ducts and plumbing. “I thought it would be with us and we’d have to learn how to live with it,” Monto says.

Monto was quickly summoned to Beijing to advise local health officials and to help the world health community size up the situation. All sorts of treatments were tried, but none were shown to work very well. In all, SARS made 8,098 people sick, of which 774 died. The new virus was identified and genetically sequenced in record time, but a vaccine would still be a long way away. “I kept saying, ‘You’re not going to be able to put the genie back in the bottle,’” Monto recalls. And then SARS simply faded and disappeared, almost as quickly as it had appeared. “Apparently the genie wasn’t very happy in humans,” he adds with a smile. “I was totally wrong, as was everybody else.” Being a true scientist, Monto is okay with that outcome too.

On his long flights and endless waits in airport lounges, Monto reads historical fiction borrowed from the Ann Arbor Public Library. This trip, it’s an Arthurian legend. “Ellyne won’t let me buy the trash in airports,” he explains. Nor can she encourage him to try his hand at her beloved crossword puzzles. Though he loves a good viral mystery, he’s just not into the word puzzles, she says. Dr. and Mrs. Monto agree that Arnold will probably never retire. “Not if I’m useful,” he says. “Not if I’m healthy enough to be doing what I feel I should be doing C9 not if I’m still making a contribution.”

“He loves what he’s doing,” Ellyne adds. “He absolutely loves it.”

Millions of people who will never hear his name should love what he’s doing too. “He is a practitioner to the whole world,” Harlow says.

Story by Karl Leif Bates, UM News Service; Photo by Myra Klarman.

Send correspondence about this or any Findings article to the editor at sph.findings@umich.edu. You will be contacted if your letter is considered for publication.

Arnold Monto was on the the front lines when pandemic influenza last showed itself, and he will almost certainly be there again when a killing global flu returns. For more than 40 years, even when nobody else seemed to be paying attention, Monto has been building the case that pandemic flu is a question of when, not if.

This story and the following related news releases are by Karl Leif Bates, UM News Service:

faculty and students wearing masks
  1. Influenza vaccines' effectiveness studied: Flu shot effective against drifted influenza, nasal spray vaccine less so.
    Dec. 13, 2006 UM News Service release
  2. Students to don masks, wash hands for influenza study.
    Nov. 28, 2006 UM News Service release