Directed Evolution: Its Utility and Risk

Amidst the Covid outbreak, the Wuhan lab leak theory sparked extensive debate, speculation, and controversy. A key focus was the gain-of-function research conducted in the lab. The field of gain of function began in 2011 when researchers from the US, the Netherlands, and Japan investigated a type of virus, the H5N1 bird flu virus. Although this virus rarely infects humans, its fatality rate stands at fifty-nine percent when it does. The researchers aimed to identify the genetic factors preventing its easy transmission to humans. Within their laboratory, they systematically re-engineered the virus into one that can easily spread among mammals while maintaining a high fatality rate. The research yielded valuable insights on how avian viruses can potentially evolve into mammal viruses that can spread in the air. However, it also faced criticism due to the perceived risk of accidentally causing a deadly global pandemic. Two years later, China’s National Avian Influenza Reference Laboratory announced that they created a whopping one hundred and twenty-seven mutant viruses through gain of function research.

Among all these controversies, one question emerges. What are the underlying mechanisms of gain of function research that allow researchers to mold the traits according to their goals? The answer lies in the fascinating realm of biology known as direct evolution.

The traditional approach to evolution was known as natural selection, a process by which traits or characteristics that confer advantages for the survival and reproductive success of an organism become more prevalent in a set population over successive generations. In the mid-twentieth century, a new concept was incorporated into the field of evolution: artificial selection. The practice of artificial selection dates back to the dawn of human agriculture. Notably, the common maize evolved from a plant known as teosinte. Teosinte, a wild grass native to Mexico, bears little resemblance to the large, sweet ears of corn grocery shoppers are familiar with today. Over generations, Mesoamerican farmers selectively bred teosinte. Those with larger and sweeter ears were bred with others with similar traits. This intentional manipulation of the plant’s genetic content through selective breeding resulted in the gradual domestication of teosinte into a more agriculturally advantageous and delicious form. This process of directed evolution differs from natural selection, where organisms are selected for their survival and reproductive success. Directed evolution allows humans to create new organisms with unique traits that may be impossible in nature. After the rise of molecular biology, a branch of biology that studies processes at the molecular level, particularly the structures and functions of biomolecules such as nucleic acids (DNA and RNA) and proteins. The 2018 Nobel Prize in Chemistry was awarded to researchers who introduced artificial selection to the molecular world. A researcher in the group, Frances Arnold developed a method to mutate proteins and subsequently assess their functionality. After the assessment, the process will repeat. This is similar to the works of the Mesoamerican farmers with teosinte, albeit without relying on sexual reproduction to generate protein offspring. In essence, this allows humans to exercise control over the evolutionary process.

Despite these advancements, a threat looms over the field of directed evolution. As of the present day, nearly all the academic research and data on directed evolution is open source and available to all. Advancements in the field of biological 3D printing allow common people to tweak the genetic compositions of bacteria, fungi, and other organisms, and print them out. Additionally, there exist websites such as the NCTC (National Collection of Type Cultures) that sell specimens of viruses and bacteria like the bubonic plague which killed as much as forty percent of the European population in the fourteenth century. The advent of directed evolution led to increased interest in tweaking these ancient specimens and cultures to reveal the boundaries and potentials. One such process is the gain-of-function research mentioned at the start of the article. A misplaced test tube or an incorrect sequence of sterilization may release these human-mutated pathogens into the world. Such alarming potentials of directed evolution underscore the need for increased methodological and ethical oversight in the field, as the consequences of a simple error may be fatal to the entire human race.

Sources:

Spieler, Eva E., et al. “Application of a biologically contained reporter system to study gain-of-function H5N1 influenza A viruses with pandemic potential.” Msphere 5.4 (2020): 10-1128.

Wang, Yajie, et al. “Directed evolution: methodologies and applications.” Chemical reviews 121.20 (2021): 12384-12444.

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The Harvard Gazette