May 2004

The cotton rat Sigmodon hispidus is a hantavirus carrier. It is found from the southeastern United States to Central and South America. Photo: CDC/ James Gathany.

Mad cow disease, bird flu, hantavirus, monkeypox. Is this just media hype or are infectious diseases on the rise?

Morse: No, I think infectious diseases really are on the rise. Of course, as we pay more attention and do a better job in recognizing these infections, there do appear to be more. But at the same time, some are new diseases that we’re seeing for the first time. For example, it’s the first time we’ve seen SARS [severe acute respiratory syndrome] in this part of the world; although it may have occurred in localized places in China in the past, it clearly reached many other parts of the world for the first time last year. West Nile, which was first introduced into the U.S. in 1999, through New York City, has now spread throughout the country. So, I think these increases are real.

The reason they’re increasing is that there are more opportunities for these infections, which may have once have been localized or very limited, to spread to larger populations by various pathways.

Many of the infectious diseases are transmitted from animals to humans, or “zoonoses.” Is this a new phenomenon?

Morse: I think it’s an ancient phenomenon. It is very likely that many infectious diseases that we take for granted were originally zoonoses, originally introduced to humans from other species. After all, we’ve been living in the natural environment with animals for a long time, and agriculture is thousands of years old.

For example, we can’t tell for sure but there’s reason to think tuberculosis, a very common and serious disease throughout the world, may have come into the human population from cattle, which have a similar organism. Over the course of time, the tuberculosis organism evolved to become a separate and human disease. Its origin is shrouded in antiquity from millennia back. It’s also very likely measles came from another species, and it, too, evolved to become the measles virus, which is specific to humans and spreads very well in the human population.

I’m sure more such examples happened in the past, and they continue to happen all the time. That’s why we see zoonoses showing up now to enter the human population.

What are the major factors that contribute to the emergence of these and other infectious diseases?

Morse: There are a number of factors, and over the years, scientists have tried to identify factors responsible for emerging infections. You can think about it as a two-step process [of introduction and transmission].

The first step is the introduction of an infection for the first time into the human population. In most cases that’s going to be an infection that’s already out there in nature—say, a virus that’s naturally infecting some other species. Often these events seem sudden. But what usually happens is some ecological change puts humans in contact with the virus. So, for example, more and more land in China is being converted to rice planting, which is a good thing to feed people. At the same time, that environment is ideal for a little field mouse, which happens to carry a virus as one of its natural infections, called Hantaan, the prototype hantavirus, and the cause of a disease which used to be called Korean hemorrhagic fever (and is now called hemorrhagic fever with renal syndrome). It’s not restricted to Korea; it can be found throughout Asia where this field mouse lives. Of course, when people clear the land for agriculture, it makes a great environment for the field mouse to thrive and live on the rice. When people harvest the rice, people get exposed to the mouse’s virus, and you see cases of disease. There are many similar occurrences around the world with different infections.

With mosquito-transmitted diseases, very often water is the limiting step. So irrigation projects, building of dams, and so on, will cause an increase in the mosquito population, and suddenly you see an increase in the diseases they carry. In Africa, for example, there is a disease called Rift Valley fever, which actually is a quite serious mosquito-transmitted disease that can affect both livestock and humans. And when they built some dams in certain parts of Africa, suddenly there was a tremendous increase in Rift Valley fever, which had not even been described there before. It probably had been there prior to the dams but at such a low level that nobody noticed it. Suddenly the expanded mosquito population presented more opportunities for people and animals to get bitten by infected mosquitoes and to contract the fever. We see examples like this all over the world.

Now at the same time, we see people moving from rural to urban areas for economic reasons. These diseases may once have been only local occurrences. Ebola, for example, whose ecology we don’t understand very well, is a natural infection undoubtedly of some species in parts of central Africa, probably living in the forest. And every so often people would encroach on the forest, say, to collect wood or do some agriculture on the forest’s edge. Someone then may become infected. And in the past, nothing much happened. There would be a local tragedy but no opportunity for the disease to move to larger populations. But now, of course, there are many opportunities—people moving into cities, people going to hospitals, where it can be transmitted.

And a very similar thing may have happened with HIV-1, the virus causing AIDS. It probably was a zoonosis, coming to us from another species. We’re not sure exactly how that happened. There were probably a lot of progenitors of HIV-1 out there in rural settings, in those natural species—possibly nonhuman primates in Africa. In the past, we can only speculate, people occasionally got infected from them, but it was very localized. Once people started to move into cities in large numbers, they could carry the infection with them, and there was a tremendous opportunity for the disease to spread through other pathways to much larger populations.

How do infectious diseases become pandemic?

Morse: A pandemic is a very big epidemic. It requires a number of things. There are many infections that get introduced from time to time in the human population and, like Ebola, burn themselves out because they kill too quickly or they don’t have a way to get from person to person. They are a terrible tragedy, but also, in a sense, it is a lucky thing that they don’t have an efficient means of transmission. In some cases, we may inadvertently create pathways to allow transmission of infections that may be poorly transmissible, for example, spreading HIV through needle sharing, the blood supply, and, of course, initially through the commercial sex trade. The disease is not easily transmitted, but we provided, without realizing it, means for it to spread. It is now pandemic in spite of its relatively inefficient transmission. We also get complacent and do not take steps to prevent its spread.

A disease like influenza is a different story. It spreads very efficiently from person to person. The right strain of influenza with the right combination of biological properties to spread well and be novel to the human population and also perhaps to come at the right time in the right place could make it easily pandemic.

So, there are many ways to become a pandemic. Luckily, it’s not an easy thing to do.

Dr. David Pimentel of Cornell University has said that millions will succumb to “death by global warming.” Do you agree with his prediction

Morse: I think that global warming is a concern in part because good science shows that increasing greenhouse gases, like carbon dioxide, seem to have the effect of leading to warming. At the same time, there is a lot of discussion about what exactly the scenario will be. The diseases that occur, where they occur, what impacts they have, will be very dependent on temperature changes and where they occur. A temperature change of several degrees may make temperate zones more hospitable to malaria, for example. And, actually, we used to have malaria in many parts of the U.S. Italy had malaria until after World War II, when it was eradicated. But it’s obviously chilling to think of the possibility of tropical diseases being introduced or reintroduced with much more serious effects into new areas. At the same time, tropical areas may become less hospitable to some of the same diseases. It’s very hard to say exactly how things will be, but, generally, it’s of concern.

Malaria alone has cost Africa billions of dollars. Is there a heavy financial cost for infectious diseases to all nations, not just developing ones?

Morse: Infectious diseases remain major causes of death worldwide. We’ve taken them, to some degree, for granted in the U.S. because we’ve enjoyed things like clean water, good nutrition, and good living conditions. These benefits have pushed once formidable infectious diseases into the background. We also have good disease control measures, such as immunization. This is not so in many parts of the world. We are also in the position where things can change.

In the case of malaria, the burden is tremendous. The World Health Organization has actually done estimates of “disability-adjusted life years”, that is, the cost of lost human labor and other economic effects of diseases. No question, these diseases take a great economic toll. The economist Jeffrey Sachs, my colleague at Columbia University, would point out that they are not only a huge burden on developing countries but they greatly inhibit developing countries from developing, by discouraging foreign investment, for example.

How can scientists stay ahead of microbial adaptation and change to get a handle on what may come?

Morse: That’s a tremendously complex question, because we know that microbes are remarkable and have been evolving for a long time. Many bacteria certainly are very ancient and have had much time to evolve. They have developed many mechanisms to evolve effectively in the face of many changes in the environment. Viruses, too.

We need to recognize these changes when they occur. We need effective early warning systems and effective ways to deal with these changes. Unfortunately, we do things to push microbial adaptation and change in various ways. Take antimicrobial resistance, for example. The development of antibiotic resistance in bacteria is greatly influenced by the way we dump antibiotics into the environment. We have to be more cautious about how we use these precious antimicrobial agents, because it’s very hard to develop them and it takes time. Microbes can evolve resistance faster than we can develop new drugs. So it’s important how we will select, in a very Darwinian way in the environment, for antibiotic resistance.

Scientists have created virus strains from scratch. Are you concerned that synthetic viruses can be used to make pathogens for biowarfare?

Morse: I think it’s a theoretical possibility, and in the future it will become more of a possibility. Right now the viruses that have been synthesized in the laboratory, basically, poliovirus and bacteriophage—a virus that infects bacteria—are ones with fairly small genomes. So it’s more a demonstration of what is possible.

Right now there are many more things in nature that already exist and are available to the potential malefactor, unfortunately. So, for the moment, nature remains the greater storehouse, for those who wish to understand the science and the ecology, but also for those who wish to take these organisms and use them for malevolent purposes.

Of course, as biotechnology advances, there will be additional capabilities. Right now, the technology is really for specialists. But as we’ve seen, as the field develops, it will become easier to do these things with less education. In the future, it is a concern. We need broad-based approaches to deal with infectious diseases. I think ultimately all of these are infectious diseases that by and large rely on certain interactions with the host—humans—and certain mechanisms for causing disease. Many of these may be bottlenecks that are common, shared by many disease-causing organisms. So understanding the mechanisms of disease and how the pathogen interacts with the host is one place we may find ways to deal with infection that could cover both the known and the unknown, both the natural and the unnatural.

Are current public health measures sufficient to curb the emergence of infectious diseases?

Morse: I think there is still a lot to do with public health. We’ve made tremendous progress in the last couple of decades. I think complacency has been a long-standing problem. This is understandable. Infectious diseases have been a scourge of humankind for a long time and, until the last 50 to 60 years, the major cause of human death globally, even in the most industrialized countries. As we developed ways to deal with these problems, we began to think overly optimistically that we could forget about infectious diseases. As the U.S. Surgeon General said in 1965, “It is time to close the book on infectious diseases.” I think we all wish it would be possible. In reality, infectious diseases will remain out there. Many infectious diseases that we’ve forgotten about in this country remain a major problem worldwide, such as malaria and tuberculosis, and could very well, given the right conditions, reappear as problems for us. In addition, there are rich opportunities for some of that great biodiversity of microorganisms to come into the human population and cause disease. We saw that with HIV, and we have been slow getting off the mark on that one. We’ve seen it more recently with SARS and influenza.

Public health is on the front lines. Surveillance for early recognition of disease problems, effective response to prevent the spread of disease, and better predictive capabilities are all essential. These traditionally have been under-resourced. We’ve tended to ignore public health. We go from crisis to crisis. When the crisis happens, we pour money into it, whether it’s mosquito control or immunization or whatever it is. Then the crisis abates and we forget the problem. We need a way to sustain public health capabilities and build better systems across the world. It is, after all, a global problem. We’re in this together.

At the same time, I see signs to be hopeful. We’re better off now than we were 10 or 15 years ago. There’s more interest in doing this. There are additional resources. And there are hopeful signs that political will is increasing. Political will is essential.

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