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.

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

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.

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