Fun Fact - Irradicating Human Diseases

For centuries, smallpox was a devastating and merciless disease, killing up to half a million people a year. In fact a common curse was "A pox upon your house!", projecting the disease upon the intended and his family. If you uttered these words in the 1700's you better be prepared for a fight. The only thing we might compare it to today is, "May cancer smite you and your entire family."

Smallpox is a viral disease, consisting of two strains: variola major, with a mortality rate of 30 to 35 percent, (80% in young children), and variola minor, with a mortality rate of 1%. If the patient survived, the small, fluid-filled blisters that are characteristic of the disease often produced permanent scars, particularly on the face. This gave rise to the word pockmark. In 2% of cases, blisters spread to the eyes and caused blindness. It was a horrific disease.

I used the past tense in the previous sentence because smallpox was irradicated in 1979 - gone from the face of the earth. Free at last, free at last, thank God almighty, free at last!

The smallpox virus is exclusive to humans, but it had to start somewhere. We believe variola jumped the species barrier some 40 thousand years ago, moving from a rodent to patient zero. Perhaps a mouse bit a hunter-gatherer while he was foraging for food, and the variola virus was perfectly mutated, at that time, and in that particular mouse, to survive and multiply in a human host. A one in a billion chance, but rare events happen if given enough time and enough trials. Since then variola has evolved into the two strains, major and minor, that comprise the disease.

Fortunately for us, debilitating pathogens don't jump from animals to humans very often - although the flu is a notable exception. Swine flu jumps easily from pigs to humans, and avian flu jumps from birds to humans. The pool of flu viruses is zoonotic, easily shared between people and animals, and is tremendously difficult to manage. (Zoonotic comes from the Greek "zoon" for animal, which also gives us zoo and zoology.) Perhaps the king of zoonotic viruses is rabies, wherein a single strain infects a wide array of mammals and birds, including humans. Transmission occurs through a bite or scratch. In contrast, the smallpox virus has been ours and ours alone for thousands of years, and was therefore a target for irradication. If we could somehow eliminate it from the human population, we would not become reinfected next year from another animal - at least it's very, very unlikely.

Unlikely yes, but still possible. We don't interact with rodents as often as we use to, but there are other pathways to monitor. Cowpox and monkeypox are similar to smallpox, infecting cows and monkeys respectively, and humans live in close association with cattle. Fortunately for us, cowpox is no longer prevalent in domestic cattle, so that is an unlikely mode of transmission. Sporadic eruptions of cowpox do occur in humans however, and these are probably caused by rodents spreading the illness to domestic cats, and then to their owners. One time in a billion this mouse to cat to human chain might carry a mutated variola that represents a new, horrible, contagious disease, requiring a rapid response. It won't be another copy of smallpox, it will be some otherpox. In order to head this off, we might advise cat owners in these regions to watch for lesions on the face and paws, and avoid handling the cat in these situations. Contact with the infected cat produces a mild instance of cowpox on the hands, and probably nothing more, but why take the one in a billion chance of becoming patient zero for a new, deadly disease? Let's throttle the animal-human transmission pathways wherever we can. (This is yet one more reason, and perhaps the best reason, not to have sex with animals.) Disease control requires ongoing vigilance, even after a particularly egregious disease has been irradicated. It's not time to sit back and put your feet up on the coffee table.

In another one in a billion example, you cannot catch distemper from your dog, even though you live together in close quarters, but distemper has spread to other mammals, including ferrets, lions, and even seals. In one critical event, thousands of years ago, distemper, or an ancestor of distemper, may have jumped from dogs to humans, because the canine distemper virus is similar to the human measles virus. Today, measles belongs to us, and an assortment of distinct distemper strains infect their respective mammalian hosts. We are rather fond of ourselves, and our pets, so we have developed vaccines for measles, canine distemper, and feline distemper.

HIV, the virus that causes aids, jumped from African monkeys to humans around 1910, probably through the consumption of raw meat. The African green monkey, the chimpanzee, and the sooty mangabey, are the probable sources of SIV, HIV 1, and HIV 2 respectively. If we stop eating bushmeat, then HIV is, for all intents and purposes, ours and ours alone, and it represents another target for future irradication.

Smallpox has no cure, but it can be prevented. As you probably know, cowpox was the tool that Jenner used to develop is commercially successful smallpox vaccine. Cowpox is close enough to smallpox to induce immunity to both diseases, without risk of contracting the latter. At worst, you might acquire a mild instance of cowpox at the inoculation site. This was safer than earlier vaccination attempts, which used smallpox materials directly, a rather risky endeavor. I don't think I'd sign up for that clinical trial.

As described above, even cowpox presents a small, long term risk, since the virus will eventually jump the species barrier and cause the very disease it is intended to prevent. When practical, modern vaccines are based on an inactive copy of the virus, or inactive viral components, which tell our immune system what to look for in the future without inducing disease. The live, albeit weakened polio vaccine is inexpensive, and can be administered orally, but it induces disease once per 750,000 doses. In contrast, the inactivated polio virus is administered by injection, which is not optimal for remote regions, but it induces disease once in 9 million inoculations. Either way, the hapless individual who contracts polio through vaccination pays the price for society's freedom from horrendous pain and permanent paralysis. Those who refuse vaccinations will probably remain healthy, because everyone around them is free of the disease, a phenomenon called herd immunity, but they are exploiting the rest of us. This "free ride" is an optimal strategy at the individual level, but not at the group level. If a critical mass goes unvaccinated, then polio will surely return. We all need to be vaccinated, and assume that tiny risk, in order to free ourselves from yet another scourge upon the land.

Smallpox was wiped off the face of the earth by a comprehensive, international vaccination campaign in the 1970's. This was an enormous undertaking, with boots on the ground in every country. Each case is tracked, including everyone who comes in contact with these contagious patients. Levels of vaccination are tallied by region, with volunteers bringing vaccines to remote areas. Considerable diplomacy is required to convince village chieftains that our medicines are benign. Given our sordid history of colonialism, oppression, and slaughter, there is reason for mistrust, but that is the task at hand. An army of trained volunteers put themselves at risk in remote war-torn regions for a greater cause, to push smallpox off the face of the earth, and they did just that. The World Health Organization (WHO) declared it "irradicated" in 1979. This may be the greatest accomplishment of the human race, reaping dividends throughout time. I place it along side the pyramids of Egypt, the moon landing, and the Human genom project.

The smallpox vaccine still exists, but people are no longer vaccinated, because the disease does not exist in nature, and every vaccine comes with a tiny cost and a tiny risk. Removing a vaccine from our childhood immunization program makes sense, but it does raise the question of an outbreak, accidental or deliberate, in a world where no one is immune. What would happen if 30% of the earth's population died from a smallpox pandemic? Books and television shows have used this plotline time and time again. It makes for a great story, but we hope it never happens, and if it does we will do our best to contain the outbreak before the disease explodes out of control, just as we manage ebola when it rears its ugly head. Some have proposed maintaining a stock of smallpox vaccines that could be deployed at a moment's notice, but these medicines have a limited shelf life, and maintaining a large inventory, decade after decade, would be prohibitively expensive.

With smallpox in the bag, how about polio? An irradication campaign is underway, with a goal of 2018. This disease is more difficult to track, because some people are asymptomatic carriers, similar to Typhoid Mary. Still, if a high percentage of the population is vaccinated, region by region and village by village, then herd immunity will keep the disease in check, new cases will not appear, and the disease will be irradicated. There have been setbacks however - recent outbreaks in Asia, Africa, and the Middle East - so 2018 is probably unrealistic. Still, we look forward to the day when polio vaccines are no longer necessary.

Rinderpest is the second disease to be irradicated, as of 2011. This is a viral disease that inflicts cattle and other ungulates. The virus is a close relative of - you guessed it - distemper. Rinderpest did not pose a direct threat to human health, but an outbreak could devastate an entire herd of cattle, with mortality rates approaching 100%. Its irradication is another giant leap for mankind. These are the only two diseases to be irradicated as of this writing.

If I were a betting man, I'd put my money on the guinea worm as the third disease to be extinguished, perhaps by 2020. This is a particularly hideous and fascinating parasite that is specific to humans. The life cycle begins in stagnant water, where larvae exist in small copepods, barely visible to the naked eye. When ingested, the larvae grow into adult worms inside the body. After a year they burst out of the skin. A meter long worm can take up to a month to creep, millimeter by millimeter, out of its human host. You can't yank it out, because the spaghetti thin worm will snap, and the remainder of the parasite will die and putrefy inside the body and lead to infection. Gentle tugging with a stick can extract the worm faster, perhaps by a week. The unremitting pain of the escaping worm is somewhat relieved by water, hence the human host places his foot or leg in the pond, whereupon the worm releases more larvae and the cycle begins again. Sometimes worms crawl out of the patients arm, or chest, or face, rather like a Stephen King horror story, but most of the time the worm extrudes from the foot or leg, so that the human can readily immerse it in water. There is no cure, and no vaccine. Irradication depends on filtered water for everyone, and isolating patients with emerging worms so they do not further contaminate the water supply. Those who might be infected must be monitored for at least a year, the incubation time of the parasite inside its human host. Once again, volunteers are putting their lives on the line, particularly in war-torn South Sudan, to put an end to guinea worm forever. This project is coordinated by the Carter Center, a nonprofit organization that is worthy of our donations. In 1986, guinea worm infected 3.5 million people each year; in 2014 there were 126 cases. We're almost there! The Carter Center is also combating river blindness and trachoma, with a long term goal of irradication.

Any disease that is exclusive to humans can, theoretically, be irradicated, but we sometimes forget that the clock is ticking. A disease can become zoonotic overnight. This is the case with malaria. Five strains infect humans, and it was hoped that these were specific to humans, whence irradication of these malarial strains is theoretically possible. However, some of these strains may be zoonotic, shared with other primates. This, combined with the ubiquity of mosquitoes, no vaccine thus far, and burgeoning drug resistance among the strains, makes malaria an almost insurmountable challenge.

My mother once asked me why such a large portion of the NIH budget was devoted to AIDS, when so many more people are afflicted with cancer. This is a reasonable question at the surface, though I fear there is an underlying subtext. "I don't do drugs and I'm not promiscuous - quit wasting my tax dollars on a disease I'm not going to get, and spend it on something that strikes everyone, including the wise and rational middle class, like me, who do not engage in risky behavior." Setting this conservative subtext to the side, the short answer is: HIV is contagious and cancer is not. It's only a matter of time before one of the HIV strains evolves into a form that can be transmitted by mosquito. That is the first step in a cascade of horrors. When most of us carry HIV in our blood, it's only a matter of time before it become zoonotic, and we are sharing HIV with other animals. At that point irradication is impossible. It's HIV management forever more. This is a horrifying prospect, and the clock is ticking. We need to irradicate HIV now, while we still can, before it figures out how to hitch a ride on the mosquito and infect us all. It really is more important than cancer, and deserving of all the research dollars we can throw at it. Of course there are two sides to every question, and though it is considerably less likely, cancer could become contageous as well. Cancer cells have been transferred by mosquito from one hamster to another. See the references below. Even if you are driven entirely by science, and not by politics, it's not an easy call.

Further Reading

Smallpox, cowpox, distemper, measles, rabies, polio,
HIV, malaria, rinderpest, and the history of vaccines
The Carter Center and the guinea worm
Contagious cancer, is it possible?