(Roughly) Daily

The obligations of a multi-day meeting (and the travel involved) mean that, from this issue, (R)D will be on pause until February 12 or 13 (depending on how connections play out…)

… and indeed the evolutionary progress of others species. But, Deputy Co-chair of the Nuffield Council on Bioethics Melanie Challenger asks, have we been sufficiently thoughful about the implications of this power?…

In 2016,  Klaus Schwab announced that we had entered the Fourth Industrial Revolution. This is the era of the industrialization of biology, the leveraging of technologies to modify biological materials to meet human goals. While the first two Industrial Revolutions exploited energy and materials and the Third exploited digital information, the current revolution is a direct manipulation of life-forms and life’s substances.  

The signature invention of this new era is CRISPR, dubbed “genetic scissors.” CRISPR is a ground-breaking method of making precise changes to DNA for a wide range of possible uses from disease reduction and elimination to the eradication of “pest” species and increases in the productivity of farmed animals. CRISPRs (the best-known system being CRISPR-Cas9) originate in RNA-based bacterial defense systems. Naturally occurring in species of bacteria, the Cas9 enzyme cuts the genomes of bacteriophages (viruses that will attack a bacterium), saving a record for defense against future infections. Scientists realized that this immunological strategy could be coopted to innovate a general tool for cutting DNA.  

The optimism among those that seek to utilize these tools has been palpable for some time. As noted by the researchers at The Roslin Institute, creators of Dolly the Sheep, the world’s first cloned mammal: “Until recently, we have only been able to dream of…the ability to induce precise insertions or deletions easily and efficiently in the germline of livestock. With the advent of genome editors this is now possible.” 

But the technologies of this new industrial era present ethical dilemmas and unknown consequences. What will it take to ensure that this revolution avoids worsening the enormous challenges we already face, especially from biodiversity loss and climate change? How can we get the balance right between the benefits and risks of human inventiveness? 

In the 1980s, tech theorist David Collingridge presented his eponymous dilemma for those seeking to control potentially disruptive technologies. First, there is an “information problem” in which significant impacts are often invisible until the technology is already in use. Second, there is a “power problem” in which the technology becomes difficult to shape, regulate or scale back once it has become integrated in our lives. If we are going to navigate the Fourth Industrial Revolution successfully, we need to examine our use of CRISPR through the Collingridge dilemma.  

The investors and engineers of the first industrial revolutions in the nineteenth century provide a vivid example of the information problem. They hoped that innovations like the combustion engine would unlock efficiency across multiple human sectors, from transportation to logistics to tourism. Such optimism was not unwarranted. Yet, as Collingridge’s dilemma suggests, it is easier to picture gains than to predict trouble. Building road systems and infrastructure carved capital movements into the landscape, symbolising freedom and the flow of wealth and creativity. Yet the striking visual parallels with our circulatory system did not stimulate anyone to forecast the ninety per cent of people today who are exposed to unsafe pollution levels from traffic or the associated health burdens from heart and lung disease to asthma. Nobody then foresaw the yearly deaths of two billion or so non-human vertebrates on our roads today, or that high traffic areas would cause localised declines in insect abundance of at least a quarter and, in some studies, as much as eighty per cent.  

And, of course, most calamitous of all, there is climate change. Traffic emissions account for a fifth of all contributions to global warming. Yet the idea that a profitable and efficient machine like the combustion engine might precede devastating shifts in temperature and weather patterns was scarcely conceivable at the time. Now, it is a near ubiquitous feature of our understanding of the world. 

When it comes to the engineering of biology, a similar information problem abounds. Not only is our understanding of biological life incomplete, but we know little about what the industrial processes that we are advancing inside the cells of organisms will do. The changes are both physically and ethically occluded. The ramifications of this and other related biotechnologies are not only rendered uncertain by the inherently complex nature of biological systems but are largely inaccessible to our imaginations.  

We must struggle with the radical character of the industrialization of biology. Gene drives (a tool to increase the likelihood of passing on a gene) can weaponize the bodies and reproductive strategies of organisms to bias evolution in a directed way. Artificial chimeric organisms (those composed of cells from more than one species) mix and match biological traits and functions to bring about beings that wouldn’t occur otherwise, transforming autonomous organisms into useful parts for plug and play. But while evolutionary processes will sift those forms and strategies that most benefit future organisms, our acts of creation primarily benefit us alone. Survival of the fittest gives way to the contrivance of the functional.  

Yet, despite the disruptive nature of these technologies, CRISPR is already entrenched in our research and economic landscape: here is the power problem of our new technology. The efficiency of modern versions of CRISPR has allowed the technology to pick up users fast. It is now a commonplace tool in labs around the world – with uses amplified during the pandemic – and continues to be utilized in ethically provocative trials, including the cloning of mammal species. CRISPR has been normalised by stealth. 

This largely uncontested rollout has been enabled by biases in the evaluation of who is at risk. Put bluntly, humans worry about humans, and take risks to non-humans less seriously. As such, there are vastly different acceptance thresholds for certain kinds of uses and these can be exploited by those that seek to deregulate or profit from the technologies…

… This discrepancy is evident in the anxieties of Jennifer Doudna, one of the Nobel-winning scientists who made the CRISPR breakthrough. In her book, A Crack in Creation, she writes of a dream in which Hitler appears to her with the face of a pig and questions her excitedly about the power she has unleashed. Doudna’s anxieties relate not to the pigs of her dream (who are subject to a wide range of CRISPR applications) but to the potential of eugenics re-emerging in human societies. Her dream reflects not only the inevitability that any technology such as this will be equal parts destruction to rewards, but also that we must confront uncomfortable ideas about what it is to be a creature as much as a creator. Recognizing that these technologies work in the bodies of all biological beings, including humans, is a continual assault on the reasoning behind a hard moral border between us and them.  

At present, the lives of non-human animals are the experimental landscape for our technologies. Their powerlessness to protest the uses of their bodies, wombs, physical materials, or futures leaves them vulnerable to being the test sites for a wide range of possible human applications. As a direct consequence of the serviceability of the bodies of organisms, CRISPR has been integrated into our world with little fanfare, directly facilitating the power problem that will, eventually, impact us too. Given Collingridge’s dilemma, what concepts and strategies could help us reduce the risks from CRISPR?

The first thing we need is a new definition of pollution. When it comes to combustion engines and other technologies of the first industrial revolutions, pollution is by far the most consequential harm. Direct impacts include the release of particulate matter or chemical compounds like nitrogen oxides or carbon dioxide into the atmosphere. Pollution from traffic has an immediate impact, especially fifty to one hundred metres from the roadside, with effects that we can measure, such as reduced growth rates or leaf damage in plants, or changes to soil chemistry and nutrient availability. On the other hand, long term effects of emissions, such as global warming, or the sustained impacts of waste on organisms and ecosystems, have proven tricky to anticipate and even harder to hold in mind…

…What is curious about the Fourth Industrial Revolution is that while several branches of science are arming us with the evidence that justifies an expansion of the moral circle to encompass a larger range of organisms, other branches are cranking up the objectification and exploitation of life-forms. As a result, there’s an obvious gap. Without addressing this, most concepts of pollution will remain anthropocentric. This may prove a critical misstep…

A provocative argument that “Gene Editing is Pollution,” from @TheIdeasLetter. Eminently worth reading in full.

See also: “The Ethics and Security Challenge of Gene Editing” and “The great gene editing debate: can it be safe and ethical?“

* Isaac Asimov

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As we ponder permuted progeny, we might send microbiological birthday greetings to Jacques Lucien Monod; he was born on this date in 1910. A biochemist, he shared (with with François Jacob and André Lwoff) the Nobel Prize in Physiology or Medicine in 1965, “for their discoveries concerning genetic control of enzyme and virus synthesis.”

But Monod, who became the director of the Pasteur Institute, also made significant contributions to the philosophy of science– in particular via his 1971 book (based on a series of his lectures) Chance and Necessity, in which he examined the philosophical implications of modern biology. The importance of Monod’s work as a bridge between the chance and necessity of evolution and biochemistry on the one hand, and the human realm of choice and ethics on the other, can be seen in his influence on philosophers, biologists, and computer scientists including Daniel Dennett, Douglas Hofstadter, Marvin Minsky, and Richard Dawkins… and as a context setter for the deliberations suggested above…

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