Quick with a smile and even faster with a pun, native New Yorker Stephen Morse doesn’t seem like a man preoccupied with mass killers.
As a boy he toyed with the idea of becoming an Egyptologist or herpetologist — “I spent a lot of time trying to catch snakes in the Pine Barrens of New Jersey” — but eventually he chose microbiology. A lifelong lover of solving puzzles, Morse gravitated toward some of the most mysterious microbes: killer viruses that seemed to strike from out of nowhere, sometimes reaching pandemic levels.
“I like intellectual challenges — that’s probably my greatest weakness,” jokes Morse, sitting in his office at Columbia University’s Mailman School of Public Health, where books, often two or three rows deep, are crammed floor to ceiling.
Morse is credited with creating the term emerging infectious diseases in the late 1980s to explain viruses that can exist for years in an animal host without causing illness. The virus “emerges” when human activity, such as habitat destruction, causes host-human contact. With the right conditions — including transmissibility — the virus infects and spreads through our species, sometimes globally.
More than 20 years after he began trying to solve one of epidemiology’s biggest challenges — understanding why pandemics happen and how we can stop them — Morse serves as the director of the U.S. Agency for International Development’s worldwide PREDICT project, which has been part of the organization’s Emerging Pandemic Threat (EPT) initiative since 2009. The program is multidimensional, from cutting-edge mathematical virus modeling to field educators teaching hunters how to reduce risk of infection from contaminated game.
On a humid New York summer day, in between fielding calls from the State Department and other eminent virologists about expanding PREDICT’s efforts into new countries, Morse explained to Discover why preventing pandemic remains an elusive goal.
Discover: Influenza is the biggest pandemic threat we face. Does the threat come from known strains evolving to be more virulent or from the emergence of a strain that’s never been seen before?
Stephen Morse: When I suggested influenza in 1990 as a paradigm of an emerging infection, (Nobel laureate) Howard Temin, a mentor of mine, disagreed. He believed it was a question of evolution, as did most microbiologists. But I think it’s a prototype in many ways. It’s fooled us every single time. It’s very complex. It has multiple hosts and can evolve by mutation but also reassortment (when two closely related strains infect the same host and exchange gene segments, producing new strains — a process distinct from mutation, when the RNA of a virus is miscoded during replication). We’re often unaware of what it’s doing in nature.
What is the mechanism for the critical step between evolving in nature and spilling over into humans, causing infection? Take us through, for example, H5N1, avian influenza A, commonly known as bird flu, which has been a problem particularly in Asia for the past decade.
SM: With H5N1, in the late ’90s there was a small outbreak of 18 cases with six deaths in Hong Kong. That’s a high mortality rate, but no one paid much attention; it was not a big deal at the time. They cleared out the markets and the wild birds and the parks, and nothing more was heard.
But the virus didn’t go away. It simply went underground, continuing to evolve in its natural host, wild waterfowl. Then it came back in 2003 and it was nasty, so evolved that a lot of people didn’t recognize it. It was far more virulent. It had been evolving during that period in its natural hosts.
It was certainly taking its toll on the poultry population. But we weren’t seeing a lot of human-to-human transmission, so we didn’t see much occasion for H5N1 to go further and take wing, pardon the pun.
Why do China and other parts of East Asia seem to be such an epicenter of influenza? Pigs are considered an ideal influenza “mixing vessel” because they are susceptible to both mammalian- and avian-based strains of influenza. And wild waterfowl, particularly migratory species, often host multiple strains of avian influenza. Is the prevalence of outbreak in Asia due to the number of animals on the continent or something else?
SM: Lewis Thomas, in Lives of a Cell, has an essay on germs that says something to the effect that all of these events are an unfinished negotiation over boundaries between the host and the pathogen. That’s really what it is. The boundaries have been set over many years, many generations with the pathogen’s natural host. We haven’t reached that degree of armistice.
When you put several species together, quail and ducks or chickens and ducks, there are opportunities for species that never get together in nature to suddenly be in close proximity and share their viruses. In its natural hosts, influenza appears to be relatively static, but when it gets into a new host, many of those constraints are lifted. It’s a renegotiation. Why do these pandemics come from China? Because China has integrated farming systems. They put two of influenza’s favorite hosts, waterfowl and pigs, together.
Is H7N9, identified earlier this year, a virus with real pandemic potential?
SM: I’m more concerned about H7N9 than I was about H5N1. H7N9 is very recently evolved. H7 has been around a while — people get conjunctivitis with it but don’t even know they had influenza. But N9 is new. It’s very rare in nature. N9 seems to have come from a wild bird, probably around Korea somewhere, although there’s evidence for rare N9s in other birds in Mongolia and Siberia, where these migratory wildfowl tend to congregate. H7N9 has to get deep into the lungs, which is why it’s not that transmissible.
If it’s not very transmissible, why does it worry you? Granted, a virus could always become more transmissible either through appropriating a piece of genetic code from a more easily spread strain (reassortment) or through its own genetic code mutating. But that risk exists for any virus. Why is H7N9 such a threat?
SM: In humans, the normal influenza receptors we have in the upper respiratory tract are not like the avian receptors H7N9 needs. It has to go deeper down, into our lower respiratory tract, to find the receptors it needs. Because it has to go deeper, once it does infect, the prognosis is not good — the risk of mortality would be high. Unlike H5N1, H7N9 could be as bad as the 1918 influenza pandemic if it were to become as transmissible because it’s unfamiliar to humans — we’ve never seen it before — and because of how deep down our receptors for it are.