A synthetic nature

Emily Hufton considers the remarkable potential, as well as the potential ethical issues, of genetically modified organisms.

Science often gravitates towards the limits of life: the phenomena of birth and death spark endless curiosity. Up until quite recently, characterising these events was enough of a challenge for many scientists. Having successfully described much of nature, scientists now seek to deconstruct it, manipulating the fundamental components of life to mould it to human benefit. Despite much public uproar, genetic modification—the bogeyman of biological science— has quickly infiltrated daily life. But recent research advances might make it even more difficult to accept.

Whilst every project starts small, this is particularly true of synthetic biology. The first genetically modified organism was a bacterium to which Boyer and Cohen introduced a gene for antibiotic resistance in 1973. Manipulation of natural methods was central to this process. Discovered two decades earlier, plasmids form the foundation of much of biotechnology. As small stretches of extrachromosomal DNA found in bacteria, plasmids often carry genes advantageous to the survival of carriers, and can be passed between different bacterial cells in a process called ‘conjugation’. Using restriction enzymes, a bacterial defence mechanism against viral invasion, genes of interest can be inserted into the plasmids, which are then taken up by host cells.

By the 1980s, scientists were no longer using these to experimentally gift bacteria with characteristics for ease of identification; rather, the quest for profit had begun. Scientists from General Electric in the U.S. were granted a patent on bacteria they had engineered to break down crude oil for bioremediation. Two years later, bacteria were being modified to produce vital human hormones for commercial use as drugs. These newfound abilities have fundamentally benefited society, allowing us to produce vast amounts of pure medicine and mitigate damage caused by pollutants. Yet they have also opened Pandora’s box.

The next step in conquering nature was mastering the molecule at its heart: DNA. Traditional genetically modified organisms usually retain most of their genomes, with genes encoding the desired characteristics inserted to supplement this. In Spring 2019, however, researchers created the first living organism with a fully recoded synthetic genome. The new strain, Syn61, was the product of extensive study and redesign of the E. coli genome. Not only does it represent the longest artificially constructed genome, the 18,000 edits also ironically revealed a great deal about the bare essentials needed to survive by removing numerous instances of degeneracy.

Modifying the result of intricate evolutionary processes was of some detriment, altering cell shape and slowing growth, but the similarity of the proteome to that of the original lab strain is a mark of the endeavour’s success. This process offers huge opportunity to the biotechnological industry, with the potential to introduce resistance to viral infection into bacterial genomes, and prevent transfer of altered genes to natural strains. These would overcome challenges traditionally associated with recombinant protein production, whether it be spoilt batches or public concern.

As controversial as they have proven to be, the GMOs that stock our supermarket shelves bear a clear and reassuring resemblance to their natural counterparts and, crucially, do not present immediate ethical issues. Whilst the Victorian Gothic and modern scientific revelations often have little in common, the construction of ‘xenobots’ at the beginning of 2020 is remarkably Frankensteinian. Assembled from African clawed frog skin and heart cells using an evolutionary algorithm, these “living robots” are capable of walking, wound healing, and cooperating with one another, and can survive for up to 10 days.

Though currently only 1mm in size and relatively rudimentary, there is the hope that one day these could play a significant role in bioremediation and human health, bypassing issues associated with more traditional machines. Possible developments include scaling up, adding a pouch for drug delivery, and incorporating blood vessels, sensory cells, and a nervous system. Here arise significant ethical issues: in potentially imbuing the creations with the capacity for feeling, the line between machine and life form becomes blurred. We have moved beyond Ginsberg’s condemned age of “robot studies in plastic cells” and into one where manipulated biology supersedes the synthetic.

Whilst these innovations look to the future, a certain sect of scientists is very much focused on the past. Using DNA preserved from now extinct species, the de-extinction movement is hoping to revive creatures of long ago. From more recent extinctions such as the passenger pigeon, to icons of the Pleistocene, the movement has caused extreme controversy but also achieved a measure of, albeit debatable, success. In 2003, an attempt to clone the extinct Pyrenean ibex bore fruit: a calf was born, but survived for only 10 minutes in huge distress. Similar suffering has historically been intrinsically intertwined with scientific breakthroughs, whether it be of the inmates participating in the Stateville Penitentiary Malaria Study, animal test subjects, or the first mammalian clones.

A utilitarian “ends justify the means” approach might be easier to apply to some of these cases than to de-extinction. Jurassic Park has ingrained the perils of dinosaur cloning in pop culture; whilst it was quite easy for viewers to anticipate potential problems in the captivity of these giant reptiles, the effects of reintroducing species to an ecosystem in which they died out are harder to predict. Aside from unforeseeable implications for food chains and human populations, de-extinction is seen by some as a diversion of funds and knowledge from the conservation and preservation of species currently under threat. Whilst a huge number of extinctions undeniably weigh heavily on humanity’s collective conscience, so might the impact of de-extinction. A perceived obligation and the potential for biological benefits must be considered in light of huge ethical and ecological concerns, which are likely to serve as a barrier to significant progress in this field.

It is undoubtedly an exciting time for science, with novel techniques empowering researchers to deconstruct the world around them and repurpose it for human benefit. Whilst this has, to some extent, defined man’s relationship with the natural world for some time, the post-genomic era has ushered in unprecedented power: a power with huge ethical implications.

This article was originally published in Issue 725 of Pi Magazine.

A synthetic nature

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