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Written by: Will Borges '24 Edited by: Melinda Li '22 Every day approximately 150 species on Earth go extinct [1]. Extrapolated out this means that every decade, approximately 10% of all species on Earth go extinct [1]. If that doesn’t unsettle you, then the fact that the rate of extinction among species is increasing should [1]. While policy-making and advocacy have provided some necessary protections, they are not enough to safeguard species from extinction. Instead, science can offer us a superior approach, one of engineering evolution itself by manipulating genetics. Engineering evolution has the potential to safeguard and reconstitute ecosystems by creating novel species with useful traits and resurrecting extinct species. Before we get into how de-extinction or inventing novel species is even a possibility, it’s important to start somewhere, so let’s start at the first modern example of genetic engineering. To set the scene, picture a warm tropical beach, colorful necklaces, and palm trees in Hawaii. The year was 1972 and this was the site of a US-Japan joint meeting on plasmids (circular pieces of DNA that exist independent of chromosomes) [2]. Dr. Stanley Cohen from Stanford School of Medicine was giving a talk on a recent technique he had developed that made bacteria take up plasmids and produce offspring with plasmid clones identical to the original [2]. At the same time, Dr. Herbert Boyer from the University of California in San Francisco was describing his data and characterizing how DNA looks after it is digested by a restriction enzyme called EcoR1, which cuts DNA at a specific predetermined sequence [2]. Soon enough these researchers were sitting together and talking about the conference when the radical idea crossed their minds: combining each other’s work [2]. The idea was that by using EcoR1 to cut two different sequences of DNA, you could then re-combine the cut sequences to form one plasmid. Following this, the recombinant plasmid could be introduced into bacteria and amplified rapidly as the bacteria divide, producing clones that all possess the recombinant plasmid. This was the birth of modern genetic engineering in the form of recombinant DNA technology [2]. Since then this technology has been employed to mass-produce insulin using recombinant bacteria. Synthetic biology is a term used to describe the interdisciplinary field concerned with the engineering of biological systems to yield useful products for humanity. Multiple discoveries in the past couple of years have made this field a hot topic of discussion in scientific circles. One of the most influential is the recent discovery of the CRISPR-Cas9 system, which acts as a natural intracellular immune system for bacteria to cut invading DNA [3]. The 2020 Nobel Prize in Chemistry was awarded to Jennifer Doudna and Emmanuelle Charpentier, the two scientists behind the initial discovery and characterization of this system [3]. Building on their work, scientists have since been able to develop CRISPR into a wide range of tools that can be used to precisely cut, modify, label, suppress and activate target DNA. This opens up interesting new possibilities seeing as restriction enzymes were limited because they could only cut at unmodifiable predetermined sequences. CRISPR can be programmed and reprogrammed to cut specific DNA sequences of interest. This means that hypothetically, joining two completely unrelated segments of DNA into a novel hybrid sequence is now more possible than ever. One way to achieve this is to use CRISPR to insert sequences from one species into host genomes from different species to yield genetic hybrids, or chimeras, with novel traits. This approach has famously been attempted by Professor Randy Lewis at Utah State University [4]. Professor Lewis has been able to successfully create goat-spider chimeras by inserting a gene responsible for producing spider silk proteins into goat embryos [4]. The chimeric goat’s milk produces spider silk protein, which can be extracted to yield spider silk [4]. This example just scratches the surface of what is possible. For example, picture bacteria that are enhanced to sequester large amounts of CO2 from the atmosphere, engineered predators that can consume invasive species like lionfish, or mosquitos that are engineered to be toxic to Malaria and other diseases. We may be able to create novel chimeric species with productive traits, but how is de-extinction even possible? The answer lies in a promising technology developed by researchers at the Wyss Institute at Harvard University: Multiplex Automated Genome Engineering (MAGE) [5]. This approach simultaneously targets multiple locations on a genome for single or multi-cell modification, producing combinatorial genomic diversity [5]. By using CRISPR to enhance this approach, evolution of new target genomes becomes a much faster and more efficient process. One of the major researchers who helped develop this technology and a leading CRISPR geneticist, Professor George Church, has laid out an ambitious vision to resurrect the extinct woolly mammoth using CRMAGE (CRISPR + MAGE) [6]. His proposal may sound crazy and straight out of science fiction at first, but he reasons that the woolly mammoth population would be useful in restoring the arctic ecosystem to mitigate the deleterious effects of climate catastrophes [6]. How would one go about this? Well first, a genome is required. This is achieved by first reconstructing a target mammoth genome from mammoth bones and frozen samples [5]. Once a target genome is secured, one has to go about breaking up the genome of a close living relative (Asian elephant in the case of the woolly mammoth) into chunks using CRISPR [5]. Then, the target genome would be used as a guide to introduce molecular changes into the elephant genome using CRMAGE [5]. Finally, a technique called interspecies nuclear transfer cloning would be used to bring the organism to life. The cloning would involve adding the synthesized mammoth genome to an elephant egg cell, shocking the egg to jumpstart its development, then implanting the egg into an elephant mother [5]. The offspring would be a de-extinct young woolly mammoth. If we do start playing around with evolution in this way, it is important that we consider the ethical implications of such action. First, it is important that we are careful not to destabilize ecosystems by engineering species that would dramatically disrupt the natural balance between producers, prey, predators, and decomposers that has been carefully fine-tuned by evolution for billions of years. Accordingly, it is important that such engineering is carefully regulated by responsible authorities. Second, while we may end up creating organisms that are productive for human societies and economies, it is important that we not allow our greed to corrupt our creations. With these technologies, Jurassic Park becomes more and more of a reality and we need not get into the issues that present themselves in a real-world Jurassic Park. Finally, we must be careful to not jump the gun before these technologies are fully ready to actualize the ambitious goals that they set out to accomplish, lest we end up creating a worse problem that will be even more difficult to fix later on. Moving forward, amazing technologies offer radical new possibilities of not only ameliorating humanity’s past errors, but also reshaping nature and humanity’s future. These technologies have the potential to be immensely powerful and are still at an early stage. As they develop and become more widely adopted, it is crucial that we proceed with the utmost caution to safeguard nature and our future. Works Cited:
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