March 2008

A colorized, electron micrograph of Influenza A virus, subtype H5N1, a fast-mutating, highly pathogenic avian flu virus. Photo: Cynthia Goldsmith

Why does it seem that viral diseases are on the rise?

Holmes: I think most emergent diseases are either newly described or increasing in their prevalence and range. The reason why we think that is most likely is that the RNA [ribonucleic acid] viruses¹ evolve much faster than an antivirus. Essentially, an RNA virus will evolve in six logs faster than human DNA. And the more you evolve, the more you mutate, the more you are able to generate mutations that will adapt you to new environments like a new host species. And, if you can get a new host species, you have a new disease. So, I think the reason why most RNA viruses are most comparable to new diseases is rooted in their basic evolutionary power, which is way more virulent.

What are some of the viruses that are a continual threat to human health?

Holmes: That is a big question; but we can look at it by grouping emergent diseases. First, there are those that are “normal” new viruses. Because they are new we don’t know what they are. Over the last few years, we have had a few of these that seemed to come from nowhere—the two most famous would be HIV and SARS. Although HIV is in monkeys and the SARS relative is in various animals, this particular virus was completely new. So there are those that are completely novel; it is difficult to predict what those are going to be.

American Red Cross tends to patients in wards set up inside an auditorium in 1918. The influenza that year may have killed 40-50 million people. Photo: Edward A. “Doc” Rogers, Oakland Public Library.

The second set consists of viruses that have been around for a long time but continue to cause problems. First, I would say, would be the rotaviruses—the rotaviruses² cause diarrhea diseases, and probably in terms of human health, they infect the most people. We don’t think about this group in the west because we can cure those diseases. In developing countries, though, such as Africa, rotaviruses are really devastating. There is also influenza, which, every year still kills about 36,000 people in the USA—a huge number. Influenza is kind of a hardy perennial disease, and every so often, it emerges with a real vengeance. For example, the 1918 influenza may have killed 40-50 million people in one year, which makes it the biggest single death toll in human history for any one event. So there are the common ones we always need to be worried about, and then added to that, are the viruses that appear out of nowhere every few years.

How is it that viruses can jump from species to species?

Holmes: That involves two things. The first thing is being exposed to a new species. As human ecology has changed, we have changed our relationship to the animal and the plant kingdom, and by so doing, we exposed ourselves to new pathogens.³ So, for example, when farming was first developed thousands of years ago, we lived near animals for the first time. That allowed us to acquire the antigens.⁴ Further on in our history, when people started to congregate in cities, disease could spread rapidly for the first time. And in more recent years, things like global air travel, deforestation, wars, changes in agricultural practices, and so on, have changed our relationship with flora and fauna. So new diseases emerged. HIV is a great example. It looks very likely that the change in land use in West Africa—when logging in proximity to monkey habitats—people acquired their viruses.

What makes the virus so unique that it can make that jump between species?

Holmes: What a virus wants is simply to self-replicate. Viruses are the ultimate parasite—they cannot exist by themselves; they need a host. So whatever species it settles in doesn’t really matter, as long as it can engage that cell. Whether the HIV infects T-cells of the chimp or an ape, it doesn’t matter. Once a virus is in the T-cell, it is going to make its life. What a virus is looking for is cells of the right kind. And if that means jumping species boundaries to find that cell, that will happen. Disease is simply a secondary effect. What viruses are interested in—similar to any natural selection process—is a numbers game. Reproduce quickly with as much progeny as possible.

Why is it important to understand the origins and the evolution of viruses?

Holmes: It is important for a number of different reasons. Emergent diseases have caused, and will continue to cause, a great human burden. As scientists, it would be beneficial to be able to predict what is going to come next. If we had predicted HIV and SARS, many more people might have been saved. Evolution gives you some rules. — about what can evolve, what can spread, and what can’t. So, if we know some rules, then we can start to predict what is going to happen.

It is also very important that, if we know how viruses and other pathogens evolve, then we are better able to treat them. One of the big problems we have at the moment—with both viral and bacterial diseases—is resistance to drugs; antibiotics in bacteria, antivirals in viruses. For example, bacteria causing tuberculosis is now resistant to three, maybe four, different antibiotics. We need to know the rules and there are new treatment strategies that actually utilize evolutionary data directly. So, evolution helps us to predict what comes next as well as to control what we have.

If we had known about evolution more in the old days, the problem that we have now with staphylococcus, for example, wouldn’t be as severe. Antibiotic resistance in bacteria is very scary—streptococcus, TB, and many other diseases. We urgently need a new generation of antibiotics to thwart that. Antiviruses are slightly different because in many cases when you have a viral infection, your infection is very short lived. Maybe three or four days at most, so by the time you go to the doctor your virus is gone. And, all you see is the immune system causing symptoms—not the virus. Antivirals are very good for diseases that last a long time, like HIV, but for quick infections, probably not so useful, because by definition you have less time to treat them. Antibiotics and antivirals are important but vaccination is more important. Vaccination is better than drugs because it prevents transmission. Medical professionals are always saying vaccines are ultimately the key, and that is true.

Why do some pathogens infect millions while others do not?

Holmes: There are a number of very critical evolutionary parameters. One of the most important—and why I mentioned previously that human evolutionary ecology has changed—is population size and density. From a human ecology standpoint, the more hosts you have, and the denser they are, the more likely the pathogen can get through and spread. So put in another way, when you are infected by a pathogen, the virus needs a new host to infect to keep itself going. If you have a small population, that is not that likely to happen. If you have a bigger population, you have more chances of transmitting the disease.

There have been some amazing studies of measles in populations. Some years ago scientists looked at islands and discovered an amazing statistic. They showed that measles can sustain itself on islands with a population size of something like 300,000 people. Below that number, measles dies out because there are not enough hosts for the virus to maintain itself. Above 300,000, it can keep itself going. So ecology plays a big role in disease.

Will viral diseases escalate in the future?

Holmes: As humans get to live in more dense environments, as the world becomes more connected , as we cut down rainforests, as we kill each other in world wars, as we make land use changes—yes, we will expose ourselves to more diseases, there is no doubt about that. However, to counter that, we are also getting better and better at working with biopathogens and learning how to control them. And, the connectedness of the world—which actually helps pathogens spread—also allows us to counter them. SARS is a great example, where global research contributed a lot to its control. So yes, we will get more and yes, they will be increasing, but one hopes as knowledge improves, that we will be able to counter them more quickly.

What do you think of the networks that now exist to control emerging diseases?

Holmes: I think they are good—much better than they were some years ago. As to whether they are ideal, we need a new test case. One thing I think we need to do is to go out into the field and find where the viruses may come from. That is a big undertaking. All of biodiversity may be a factor because viruses come from animals that live on this planet already. So potentially, although it is very hard to do, we could screen all the pathogens that live in animals on Earth. This might sound like science fiction but I don’t see why it couldn’t be done in the future. The technology is slowly getting there where it might be possible.

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