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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Skipping Generations, Part 2

A few weeks ago, I wrote about traits skipping generations. Be sure to read that entry to get caught up. Genes that are located on the X-chromosome sometimes, but not always, lead to traits skipping generations. But this is not the only way traits can skip generations. Skipping generations can also occur with genes that are not located on the sex chromosomes. The rules of inheritance are such that, given the right combination of alleles in parents, traits can sometimes skip a generation.

When sexual reproduction occurs, the offspring gets a random combination of alleles from their parents. Each parent has two copies of each gene, and one of those copies from each parent is given to each offspring. There are four possible alleles to choose from — two from each parent — and each offspring gets one at random from each parent. This is exactly the same way it works for the sex chromosomes.

Here is one way a recessive trait can skip a generation:

In genetics, it is the convention for dominant alleles to be expressed with a capital letter, and recessive alleles with a lower-case letter.

The parents in our first generation are Sam and Jess. Sam has two copies of the dominant allele (“AA”) — which causes him to express the dominant trait — and Jess has two copies of the recessive allele (“aa”) — which causes her to express the recessive trait. It doesn’t matter what the trait is. It could be attached vs free earlobes, widow’s peak, knuckle hair, or any other trait that follows the basic rules of inheritance. (There are traits that follow slightly different rules, but I’m not going to talk about them right now.)

When they have children, every child will get an “A” from Sam and an “a” from Jess, because Sam has only “A’s” to give, and Jess has only “a’s” to give. All of the children will express the dominant trait, although they all carry (but do not express) the recessive allele. Unlike with x-linked traits, the expression of these traits is not related to sex.

Ann grows up and marries Luke, who is also “Aa.”

There are four possibilities for the children:

(1) They can inherit Ann’s “A “and Luke’s “A” (“AA”).

(2) They can inherit Ann’s “A” and Luke’s “a” (“Aa”).

(3) They can Inherit Ann’s “a” and Luke’s “A” (“aA”).

(4) They can inherit Ann’s “a” and Luke’s “a” (“aa”).

Options (2) and (3) result in the same combination of alleles — “Aa” — even though the source of the alleles are from different parents. That is, it doesn’t matter whether the “A” comes from the father or the mother. It will always be dominant over the “a.”

In the three generations of this family, the recessive trait is only expressed in one individual in generation 1 (Jess), and in one person in generation 3 (Tim). Nobody in generation 2 expressed the recessive trait, even though people in generation 2 carried the recessive allele.

As I said before, these types of traits only sometimes skip generations, but do not always skip generations. By changing the genetics of the example above only slightly, the scenario will play out very differently. If Sam is “Aa” instead of “AA,” half of his children with Jess will be “aa” and the other half will be “Aa.” The recessive trait will be expressed in the second generation and there will be no skipping of generations.

Sometimes generation skipping can happen with dominant traits, too, although by a slightly different mechanism. Recessive alleles can be carried by individuals who do not express the trait, making it easy for the recessive traits to be silent. The only way for a dominant trait to skip generations is if the dominant allele is not passed on in a family, and it is then added in a subsequent generation.

For example, Jim (Aa) and Jill (aa) have children. There is a 50% chance that any child they have will inherit an “a” from both parents. If they have two children, there is a 25% chance that both of them will be “aa.”

Their daughter, Liz, grows up and marries Bill, who is also “aa.” Since neither of them has any “A” alleles, all of their children will be “aa.”

Their son, Rob, grows up and marries Kim, who is “AA.” All of their children will be “Aa.”

Between the first and second generations, the “A” allele was removed from the family lineage. It was not until Kim that the allele was introduced back into the gene pool. The dominant trait skipped generation 2 entirely. Again, this is not because of something to do with the trait itself — the various allele combinations of everyone interacted in certain ways to make the trait skip a generation.

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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.

 

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What Do Plants Eat?

Image from “Little Shop of Horrors.” Linked from filmlinc.com

Most of us are taught in school that plants make their food out of sunlight. While this is true in some sense, it is easy to miss what is really going on inside plants. Plants are sometimes depicted as receiving sustenance directly from the sun, just as we do from eating food, but this is not correct. I recently encountered a person who, upon hearing that plants make their food out of sunlight, believed that plants harness Einsteinian physics to convert energy into matter. This is not such a strange thing to believe, given the ubiquity of the “plants eat sunlight” meme. I want to set the record straight in this post.

So what do plants eat? The short answer is that they eat glucose. Glucose is a simple sugar and it is the same thing a lot of other organisms eat for food. What’s different about plants (as well as some bacteria and protists) is that they make their own glucose. When animals want to eat glucose, they need to eat something that is already made of it. When we eat plants, a lot of the nutrition we are getting out of it is the glucose. Unlike animals, plants have the ability to build glucose out of other molecules — carbon dioxide and water. Once plants have built glucose, they can use it as a building material and they can us it as food.

But what is food really? Food is energy stored in chemical bonds. When the chemical bonds are broken, the energy is released and can be used to power different body functions (a few more steps are involved, but this is the short version). Carbon dioxide and water are relatively low-energy molecules. Glucose has much more energy, and turning carbon dioxide and water into glucose requires the addition of energy. Plants harness the sun’s energy to make this happen. Glucose molecules are therefore vaguely analogous to batteries. Breaking down glucose into carbon dioxide and water is like releasing the battery’s charge, and combining them back into glucose is like recharging the battery.

So do plants make their food out of sunlight? In one sense, glucose is made out of carbon dioxide and water, not sunlight. In another sense, the point of making glucose is to capture the energy from the sunlight. Water and carbon dioxide combining to form glucose is the vessel that carries that energy.

Venus Flytrap. Image from wikipedia.org

What about carnivorous plants, like the pitcher plant, venus fly-trap and sundew? These plants have evolved to trap, kill and digest animals. Carnivorous animals eat other animals for the protein and fat, but this is not the case for carnivorous plants. Plants need carbon dioxide and water to make glucose, and carnivorous plants are no different — but these are not the only molecules that plants need to thrive. Plants need to make proteins and other molecules that cannot be built using only carbon dioxide and water. These require nitrogen, phosphorous, potassium, calcium, and other molecules. Carnivorous plants live in environments where these other nutrients are rare, and it is these nutrients that carnivorous plants are after when they eat animals.

 

 

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