Tag Archives: Disease

The Man Behind the Curtain Turns 1

The Man Behind the Curtain turns 1 today! In the past year, this blog has had over 4800 views from people in 104 nations. This surpassed what expectations I had, and I am looking forward to another good year.

The most popular posts this year were:

Dinosaurs are not Extinct

Hot or Not

Do genes skip generations?

Testing a Claim: Ceramic Knives

The least popular posts were:

Drug-Resistant Diseases

Skipping Generations Part 2

You’re Doing it Wrong, Part 2: Post Hoc Ergo Propter Hoc

A UFO (which was my first post)

And these are my personal favorite posts:

For All Mankind

Dinosaurs are not Extinct

10% of our Brains

The Evolution of Flight

Thanks for reading! I hope 2015 will be even better. (Tomorrow I will go through and fix all of the broken images. Sorry about that.)

Have a topic you want me to cover? Ask in the comments section or on Twitter @CGEppig

Follow me on Facebook


Drug-Resistant Diseases

Drug-resistant pathogens are in the news more and more these days. The World Health Organization recently released a report about the declining effectiveness of antibiotics. Many believe that the age of antibiotics is coming to an end. This is very troubling, given that antibiotics are unquestionably one of the greatest advancements in the fight against disease.

Infectious diseases are caused by a variety of organisms: viruses (HIV, chicken pox, dengue fever, ebola, influenza, rotavirus), bacteria (tuberculosis, meningitis, gonorrhea, tetanus, whooping cough), worms (schistosomiasis, ascariasis, whipworm, pinworm, elephantiasis, river blindness), protists (malaria, sleeping sickness, giardia, leishmaniasis, chagas disease, cryptosporidium), and fungi (athlete’s foot, thrush, valley fever, aspergillosis).

Organisms that cause disease (such as those listed above) are not fundamentally different from the organisms that do not cause disease. Parasites are subject to evolution by natural selection just like anything else.

A toxin may broadly be defined as a chemical that negatively affects the physiology of an organism when the two come in contact. Drugs that we use to fight parasitic infections within a person’s body are toxins. Ideally, the toxicity of the drug is much greater to the parasite than it is to the host.

There are many naturally occurring toxins in the environment. Ethanol, along with many other alcohols, is a very powerful toxin to most living things. It is because of this toxicity that we use various alcohols to sterilize various surfaces (including our hands, in the case of hand sanitizers) and sometimes instruments.

Humans have a fairly high resistance to ethanol, but not to other alcohols. Most people can drink the equivalent of a couple of ounces of pure ethanol and be fine. The same quantity of methanol or propanol (which are chemically very similar to ethanol) would lead to pretty severe physiological consequences, including death. The ability of humans to metabolize ethanol is attributed to our evolutionary history of eating fruit. Fruit contains a lot of sugar, which is a good source of energy. Ancient people who ate fruit whenever it was available had more energy available in their bodies for building muscles, repairing damage, reproduction, hunting, and whatever else they needed to do. If fruit sits on the tree (or the ground) too long, yeast lands on it and starts eating the sugar for itself. When yeast eats sugar, ethanol is produced as a waste product. If a person eats that fruit, they will also be eating some ethanol. A person who is able to withstand a lot of ethanol is able to eat a lot of fruit and gain the energetic benefits of doing so. Over time, the average human became more and more able to cope with consuming toxic ethanol. Modern humans can safely consume quantities of ethanol that would be fatal to many other organisms.

Methanol, ethanol and propanol are all very similar molecules. Ethanol is the only one we can consume.

Methanol, ethanol and propanol are all very similar molecules. Ethanol is the only one we can consume.

So what does any of this have to do with diseases? Just as humans evolved to cope with the toxicity of ethanol, pathogens can evolve to deal with the toxicity of the drugs we use to fight them.

The most toxic substance to an organism is going to be one that is “evolutionarily novel” — that is, the substance is one that the species has not encountered over its evolutionary history. Why? Because a species that frequently encounters a particular toxin will evolve physiological mechanisms to resist the negative effects of the toxin. For example, if you want to poison a human with an alcohol, you’d use methanol, not ethanol, because ethanol is more evolutionarily familiar to us.

When we use the same drug to fight the same pathogen over many years, the drug becomes evolutionarily familiar to the pathogen, and the pathogen can evolve to cope with it. For decades, physicians used the same antibiotics to treat bacterial infections, including those caused by Staphylococcus aureus. After they used the antibiotic methicillin for a long enough time, the methicillin became a normal part of the bacteria’s environment and the bacteria evolved to cope with it, eventually becoming Methicillin-Resistant Staphylococcus aureus, or MRSA.

The rate of evolution for any given species is inversely-related to the generation time of the species — species with long generation times evolve very slowly, and species with short generation times evolve very quickly.

Organisms with a shorter generation time evolve faster

Organisms with a shorter generation time evolve faster

This is because evolution is a process that happens in between generations. If new generations occur more closely together, more evolution can happen in a shorter time. The human generation is about 20-30 years. A generation for bacteria can be as short as 20 minutes — that’s 72 generations per day, over 26,000 per year, and over a half million within the span of a single human generation. For perspective, a half million human generations is about 10 million years. 10 million years ago, gorillas, chimpanzees and humans had not yet evolved into separate species. What does this mean for antibiotic resistance? It means that bacteria can evolve very quickly to be immune to a given antibiotic.

This is obviously bad news for us. Not all pathogens evolve as quickly as bacteria, but they are all pretty fast. Recent history is full of examples of drugs that worked well until the disease evolved immunity towards it.

Malaria, tuberculosis, HIV, Staphylococcus aureus, Escherichia coli, gonorrhea and many others all have strains that have evolved immunity or resistance to the drugs we use to treat or cure them. We are going to need a new way of fighting these diseases.

Have a topic you want me to cover? Let me know in the comments or on twitter @CGEppig


Are Humans Still Evolving?

Image from telegraph.co.uk

I hear this question come up a lot. The subtext is that, because humans have mastered our environment, we are no longer subject to the same pressures of natural selection that we once were.

First, let’s review what evolution is. Evolution is a change in the frequency of alleles or traits in a population over time. Natural selection is the mode of evolution where the change is based on environmental pressures that cause individuals with certain traits to reproduce more than individuals without those traits. Natural selection does not have a goal, or a more or less advanced state. Natural selection improves a population in that it increases the frequency of traits that cause the members of the population to leave more surviving offspring. It does not improve a population by necessarily making the individuals smarter, faster, stronger, or more complex. A cheetah is not more evolved than a sloth because it is faster. Both were designed by natural selection to do what they do.

Infectious disease was a huge problem for our ancestors. Good thing we cured them all. (In case there was any doubt, that last sentence was full of sarcasm.) While it is true that medical advances have greatly reduced the burden of infectious disease in the west, they are still a big problem in most of the world. Malaria, tuberculosis, HIV/AIDS, respiratory infections, and diarrheal disease each kill over a million people a year worldwide, mostly in developing nations.

Even in the medically-advanced United States, tens of thousands of people die every year from influenza alone. We may not have schistosomiasis or malaria, but we still have people dying of infectious disease in large numbers. If there exist any alleles in our population that confer resistance to diseases that we face, however slight, then we are evolving. If for example, people with a particular allele have even a 0.1% increased chance of surviving influenza, then that trait will increase in frequency in subsequent generations.

If diseases are not killing us randomly, then those diseases are causing us to evolve. If we cure those diseases, then the cure will also cause us to evolve. If a disease is killing people who do not have a particular trait, then the frequency of that particular trait will increase. If we cure the disease, then the frequency of that particular trait will begin to decrease again. Both the increase and decrease of the trait frequency are evolution. I think this is where a lot of people get hung up — because we are not “improving” we must not be evolving.

Our evolution is not limited to the effects of infectious disease. If you look at population growth in the world, it is not the same everywhere. Traits that occur at higher frequencies in the parts of the world with higher fertility rates will get passed on at a higher frequency. This is also evolution.

Average fertility rate by country. Most of the world’s population growth is happening in central Africa. Image from wikipedia.org

Evolution takes place over the course of many generations. Individual human observers will therefore have a difficult time observing human evolution. It may not look like we are evolving, but we certainly are.

 

Have a topic you want me to cover in a future post? Let me know in the comments or on twitter @CGEppig.


The Truth About Zombies

As I sat down today to play The Last Of Us, I thought, as I sometimes do, about the actual possibility of zombies. I have always been a big fan of the zombie genre. In movies, TV and video games, zombies can be broken down into two types. The first are the ones that are raised from the dead through some sort of magic. (See: Dead and Breakfast, Dead Snow, The Evil Dead). The second type are the result of natural causes (that is, not supernatural). Sometimes the cause is a toxin, but it is much more typically an infectious disease.* (See: 28 Days Later, Quarantine, Resident Evil.) As a biologist, this second type has always appealed more to me.

There is a certain degree of biological plausibility to this premise. The primary “goal” of pathogens, like all other life forms, is to reproduce.** To this end, many, if not most, pathogens further their goal by controlling the behavior and physiology of their hosts in ways that increase the chance of infecting other hosts. This is broadly called “host manipulation.”

Take the common cold, for example. As a respiratory virus, the cold is spread through exposure to fluids from the mouth, nose and throat. The symptoms of this virus include runny nose, sneezing and coughing. The sneezing and coughing cause the virus to be spewed into the air and onto nearby people and objects. The runny nose makes you touch your face frequently and get the virus particles (which are called “virions”) on your hands, which are then left on anything or anybody you touch.

Zombies are an example of a fictional parasite manipulating the host. Consider the properties of modern zombies in film, TV and video games: They are compelled to seek out uninfected humans and attempt to bite them. The bite transmits the infection and the bitten person becomes a zombie. Infected people only attack the uninfected. These behaviors all help to spread the infection. 28 Days Later (one of my favorites) went one further: the “rage virus” can be transmitted through any exposure to blood, not just a bite. The zombies in this film vomit blood everywhere so that an actual bite is not always necessary. (I couldn’t find a youtube clip of this. If you happen to find one, please post it in the comments.)

Here are some other real parasites that manipulate their host’s behavior:

Ophiocordyceps unilateralis: This fungus belongs to a larger group of fungal parasites that aggressively infect insects and arachnids, eventually killing the host. This particular species, which infects ants, controls the behavior of its hosts before it kills them. Ants infected with O. unilateralis will climb high into trees and bite into a leaf to anchor themselves against the wind. The ant will die, still clinging to the leaf, and the fungal spores will be released into the wind, where they can spread farther than they would have from an ant that died on the forest floor. In the video game The Last of Us, the zombies are caused by a fungal infection called “cordyceps,” which is presumably a relative of O. unilateralis.

Ants in the late stage of O. unilateralis infection. Image from wikipedia.org

Rabies: The rabies virus can infect many species of mammal. The virus is concentrated in the saliva of the infected animal and is transmitted by bite. Infected animals become very aggressive and try to bite other animals including humans. The characteristic “foaming at the mouth” is just an excess production of saliva, which contains the virus. A rabies infection causes the host to avoid water — another name for rabies is “hydrophobia.” If the animal were to drink water as normal, the virions concentrated in the host’s mouth could be washed away and the virus’s ability to infect others would be diminished. There are videos on youtube that purport to show this, but I cannot vouch for their authenticity. **minor spoiler alert** In the movie Quarantine, it turns out that the zombies are the result of a mutated strain of rabies. This was a good call, since rabies already has most of the characteristics of a zombie infection.

Toxoplasma gondii: Toxoplasma is a parasitic protist that has a multi-stage life cycle. One stage is in rodents, such as mice. The next stage is in cats, who contract the parasite by eating infected mice. Cats eat plenty of mice on their own, so they are at risk of contracting toxoplasmosis*** without any help. But it is better for the virus if the cats do get a little bit of help. Mice are normally pretty good about avoiding cats. After all, mice who are better than others at not being eaten will be alive longer and therefore able to produce more offspring — natural selection works. But mice which are infected with Toxoplasma do not fear cats. On the contrary, they are attracted to the smell of cats. A hungry cat is happy to eat an easy meal, but will unknowingly contract toxoplasmosis in the process. The parasite is subsequently spread by cat feces, so it does not need to manipulate the cat’s behavior.

Mice infected with T. gondii do not fear cats. This mouse appears to be healthy. Image from crossfit707.com

Mice infected with T. gondii do not fear cats. This mouse appears to be healthy. Image from crossfit707.com

Dicrocoelium dendriticum: D. dendriticum is a parasitic flatworm that has a multi-stage life cycle a little bit like T. gondii. One stage is in an ant, and the next stage is in grazing herbivores like sheep or cattle. Being herbivores, sheep and cattle do not go out of their way to eat insects, but neither will they pick bugs out of their food if there are any in there. An ant infected with D. dendriticum will climb to the top of a blade of grass and hold on. By virtue of their location, they are more likely to be eaten by a herbivore. Unlike in T. gondii, the ant being eaten by the next host is incidental, not intentional — the cat wants to eat the mouse, but the sheep is indifferent to eating the ant. Once the ant has been eaten, the parasite will continue the next stage of its life cycle.

Crawling to the top of a blade of grass and holding on is not normal behavior for an ant. Image from en.citizendium.org

These are just a few interesting examples of host manipulation. There are many more.

All of this is not to suggest that the zombie apocalypse is imminent, but it is not particularly out of the question — there is precedent for diseases manipulating behavior in some fairly dramatic ways. The only primary aspect of zombies that is not plausible is for an infection to reanimate the dead, which some people consider to be a defining characteristic of zombies. If a disease is to control your behavior, it doesn’t need to kill you to do it. Death occurs because your body is no longer able to maintain homeostasis and fight entropy. No parasite has the energy or machinery to rebuild a dead body into working order. It is much more efficient to infect a living organism and to not kill it before the parasite has spread. People sometimes disregard 28 days later as not a real zombie movie because the people are just sick, not risen from the dead. I would argue that it is the most real zombie movie for exactly the same reason.

*There are also movies in which the cause of the zombies is not explained. Natural causes and supernatural causes are still the only possible options.

**Pathogens obviously lack the cognitive properties to have goals in the sense that we humans have goals. When I say that they have a goal, I mean that their physiology and behavior were designed by natural selection to accomplish a particular task.

*** Toxoplasma is the name of the disease-causing organism. Toxoplasmosis is the name of the condition caused by a Toxoplasma infection.

Have a topic that you want me to cover? Let me know in the comments section.

Follow me on twitter @CGEppig