Darwin's Reach

21st Century Applications of Evolutionary Biology

Norman A. Johnson

• Publisher: CRC Press
• Year: 2021
• ISBN:
  9780429995477
• Edition: 1
• Topic: Ciencias biológicas
• Subtopic: Evolución

The application of evolutionary biology addresses a wide range of practical problems in medicine, agriculture, the environment, and society. Such cutting-edge applications are emerging due to recent advances in DNA sequencing, new gene editing tools, and computational methods. This book is about applied evolution – the application of the principles of and information about evolutionary biology to diverse practical matters. Although applied evolution has existed, unrecognized, for a very long time, today's version has a much wider scope. Evolutionary medicine has formed into its own discipline. Evolutionary approaches have long been employed in agriculture and in conservation biology. But Darwin's reach now extends beyond just these three fields. It now also includes forensic biology and the law. Ideas from evolutionary biology can be used to inform policy regarding foreign affairs and national security. Applied evolution is not only interdisciplinary, but also multidisciplinary. Consequently, this book is for experts in one field who are interested in expanding their evolutionary horizons. It is also for students, at the undergraduate and graduate levels. One of the public relations challenges faced by evolutionary biology is that most people do not see it being all that relevant to their daily lives. Even many who accept evolution do not grasp how far Darwin's reach extends. This book will change that perception.

Key Features

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• Emphasizes the expanding role evolutionary biology has in today's world.

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• Includes examples from medicine, law, agriculture, conservation, and even national security

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• Summarizes new technologies and computational methods that originated as innovations based in part or whole on evolutionary theory.

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• Current. Has extensive coverage of the COVID-19 pandemic and other recent topics.

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• Documents the important role evolution plays in everyday life.

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• Illustrates the broadly interdisciplinary nature of evolutionary theory.

Resources

The applications of evolutionary biology are far too numerous to include in just one book. Plus, new scientific findings emerge almost every day underscoring the central role evolution plays in our lives. The author has established a blog site to highlight these fascinating discoveries. Please visit https://darwinsreach.blog to be inspired by "… endless forms most beautiful and most wonderful [that] have been, and are being evolved." (the last line of Charles Darwin's The Origin of Species).

Section I Health

1 Paging Dr. Darwin Evolutionary Medicine in the 21st Century

DOI: 10.1201/9780429503962-2

SUMMARY

A major problem in medicine is antibiotic resistance: as bacteria evolve resistance to antibiotics, the effectiveness of this essential treatment soon declines. This chapter begins with a new treatment designed to inhibit the evolution of resistance with (bacterio)phages, viruses that attack bacteria. In adapting to a specific type of phage, the bacteria are forced to evolve less resistance to antibiotics. Bacteria that cannot be resistant to both the phage and antibiotics are an example of a tradeoff, a fundamental concept in evolution. The chapter then discusses other ways of using evolutionary principles to limit the evolution of antibiotic resistance. The applications of evolution to antibiotic resistance are a subset of the larger field of evolutionary medicine. A central question within evolutionary medicine is why we get sick and remain vulnerable to disease. Some explanations include the more rapid evolution of pathogens and parasites compared to our own, that some symptoms of illness (such as fever) are actually defenses against infectious disease, mismatches between the environments we live in and those our ancestors evolved in, and that natural selection favors traits that enhance reproduction and not necessarily our health or our happiness.

“Evolutionary biology offers a framework for organising the diverse facts in medicine, and a way to understand why the body is vulnerable to disease.”—Randolph Nesse.¹

FIGHTING RESISTANCE IS NOT FUTILE

In 2012, Dr. Ali Khodadoust, then a 76-year-old ophthalmologist from New Haven, Connecticut, had coronary bypass surgery. Soon after surgery, complications ensued: Khodadoust developed a bacterial infection coming from the graft the surgeons had used on his aorta. The infectious agent was the bacterium Pseudomonas aeruginosa, one commonly found in hospitals. Pseudomonas usually is not harmful, but it can be for people who have deficient or compromised immune systems. Due to his open-heart surgery, Khodadoust’s immune system was likely impaired.²

Despite multiple treatments with antibiotics, Khodadoust’s infections kept reoccurring.³ The Pseudomonas quickly had evolved resistance to the antibiotic ciprofloxacin. Khodadoust became septic. His doctors determined that the bacterium was not completely resistant to a different antibiotic (ceftazidim), which they gave him intravenously. After several weeks, the infection was sufficiently reduced. But soon after, it came back again. By 2015, Khodadoust seemed to have exhausted his options.

Khodadoust’s story is just one example of the growing threat of antibiotic-resistant bacteria. Almost as soon as one antibiotic becomes commonly used, bacteria evolve resistance to it. Bacteria replicate quickly and generate large numbers, attributes that are conducive for very rapid evolution. Moreover, bacteria have the capacity to transfer genes across to even relatively distant relatives through a variety of mechanisms. This process—lateral gene transfer—also contributes to the ability of bacteria to evolve antibiotic resistance. In particular, P. aeuruginosa is adept at evolving resistance, having many genetic mechanisms of resistance available to it.⁴

How can we mitigate this resistance threat? One idea arises from the natural history of bacteria. Like just about every other life form, bacteria have natural enemies. Usually, the biggest threats to bacteria are bacteriophages—“phages” for short—viruses that specifically target bacteria. The word “phage” comes from the Greek “phagen”, in English, “to devour”. And phages are proficient at devouring their bacterial hosts! Many phages look like space capsules. They dock at a receptor site of the bacterial cell and insert their DNA. This phage DNA then is replicated many times. Here the bacterium does the heavy lifting: the phage DNA is replicated by the machinery the bacterium uses to replicate its own DNA. How devious! These phage DNA segments are packaged into capsules, which then bust through the cell, leaving devastation. The cycle is then ready to repeat, only with many phage capsules instead of just one. With just a few such cycles, bacterial infections can be wiped out.

What if one of these phages could be used to thwart the antibiotic-resistant bacteria infecting Khodadoust and others like him? This idea—phage therapy—has a long and murky history. Phages were used to treat bacterial infections from almost as soon as they were discovered in the early part of the twentieth century. Outside of the countries dominated by the former Soviet Union, phage therapy was largely abandoned for many decades. As we will see, this treatment, with some new twists, has been making a comeback in recent years.

The French Canadian virologist Felix d’Herelle dominates the early history of phages and phage therapy.⁵ Well-connected, peripatetic, and largely self-taught, d’Herelle had an interest in the transmissible particles that could eat through bacteria, causing what he called “taches vierges” or “clear plaques” on bacterial lawns. In the summer of 1915, an outbreak of severe hemorrhagic dysentery swept through French troops stationed outside of Paris. While stationed at the nearby Pasteur Institute, d’Herelle investigated the cause of the dysentery. He noticed that these transmissible particles would also devour the Shigella bacteria that had caused the soldiers’ dysentery. Perhaps, he thought, these particles—which we now know as phages—could be used to treat infections.

Also working at the Pasteur Institute was a virologist from the then Soviet Republic of Georgia, George Eliava. The younger virologist caught d’Herelle’s enthusiasm for phages and phage therapy, leading to him to establish the Bacteriophage Institute in the Georgian city of Tbilisi. Phage therapy studies flourished at Tbilisi. Unfortunately, Eliava did not. Because he had angered Stalin’s friends, Eliava was named an “enemy of the people”. He was executed in 1937.

Research on and applications of phage therapy continued during the second half of the twentieth century in the Soviet Union and the associated Eastern Bloc. Phages were even used as a preventative measure in schools, military bases, and other areas where large numbers of people were in close association due to the enhanced risk of rapid outbreaks in such localities.

With the advent of the effective antibiotics, the interest in phage therapy waned outside of the Soviet Union. Still, as an ever-growing list of antibiotics lost their effectiveness due to bacteria evolving resistance, phage therapy is staging a revival. One of the limitations of phage therapy is that bacteria can also evolve resistance to the phage. This limitation is mitigated, though not completely, by the prospect of phages evolving to counteract the bacterial resistance. Such coevolutionary arms races are frequent in nature.

Ben Chan and Paul Turner, who are evolutionary biologists at Yale University, have developed a new approach to using phage therapy that takes explicit advantage of bacteria evolving in response to the phage. They identified a particular phage that could make the bacteria less resistant to antibiotics as the bacteria evolve responses to it.⁶ This phage, known as OMKO1, was found in water samples from Dodge Pond in East Lyme, Connecticut—not far from Yale’s New Haven campus.

Here’s how it works. The OMKO1 phage devours the bacteria. Variation exists within the bacteria in how vulnerable they are to the phage. Over time, the bacteria that are best able to withstand the phage persist and divide, leaving a population of bacteria that are more resistant to the phage. Nothing surprising is happening—this is simply the evolution of resistance to the phage. But there is a twist here. The bacteria that are resistant to the phage have different efflux pumps than those that are sensitive. The efflux pumps are protein-based structures located on the bacterium’s cytoplasmic membrane that transport chemicals. While making the bacteria more resistant to the phage, this change in the efflux pumps also makes the bacterial cells less resistant to several mainstream antibiotics. The bacteria face a tradeoff that traps them in a box: they can be resistant to the phage or they can be resistant to the antibiotic, but they cannot be resistant to both. This double whammy of the phage and the antibiotics ought to keep the Pseudomonas infection in check.

Chan and Turner and their team then used the phage to treat ophthalmologist Ali Khodadoust. They applied a cocktail of the phage and the antibiotic ceftazidime at the site of the infection.⁷ Soon after being given the phage cocktail, the bacteria infecting him became less resistant to several antibiotics. With reduced resistance, the bacteria could be brought under control by antibiotic treatment. Khodadoust’s infection was cleared, likely allowing him a couple extra years of higher quality life and the ability to resume his ophthalmology work. He died in March 2018 at the age of 82.⁸

Surgery patients are not the only ones who are susceptible to invasion by Pseudomonas and other opportunistic bacteria. So are people who have cystic fibrosis, a genetic disease that causes a buildup of mucus in the lungs.

Cystic fibrosis is due to mutations in a particular gene known as the cystic fibrosis transmembrane conductance regulator. Yes, that’s a mouthful. Hence, the gene often goes by the moniker CFTR. But its full name provides clues as to what the gene does. The word “transmembrane” means “across a membrane”. Our cells are replete with membranes. The membrane here is the outer one of the cells that provide a protective lining of our lungs. Conductance sounds like something involved with electricity. In fact, it is the movement of ions, charged atoms. Here, the ions are chloride ions, one of the components that make up ordinary table salt (sodium chloride). So this gene provides information to produce a protein—an ion channel protein—that rests inside the membrane of cells lining the lungs. This ion channel protein regulates the balance of ions by pumping chloride ions out. A person who has two mutated versions of this gene will have cells that are less adept at transporting those chloride ions out of the lungs. As a consequence, their lungs will become salty, leading to a buildup of mucus in the lungs.⁹

In the absence of the phage, the bacteria are resistant to the antibiotic in part because their open efflux pumps allow for easy removal of the antibiotic. In the process of adapting to the phage, the bacteria evolve efflux pumps that are more closed. This change makes the bacteria less resistant to the antibiotic.

Source: Illustrated by Michael DeGregori.

One cystic fibrosis patient, a 22-year-old woman, came to Chan’s team in October 2017 to see if the phage would work for her.¹⁰ Over the next two months, the team examined whether the OMKO1 phage could work on her infection. Spoiler alert: it could! After they received approval from the FDA and other regulatory bodies, the team treated her, giving her the phage cocktail that she could self-administer with a nebulizer. Even after just two days, her infection also quickly responded, and she had more energy. Although the bacteria had not completely cleared after a ten-day ...