Posts Tagged ‘genes’
“The advance of genetic engineering makes it quite conceivable that we will begin to design our own evolutionary progress”*…
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…
“Without mysteries, life would be very dull indeed”*…
Colonoscopies are a right of passage into late middle-age. One dreads getting a “surprise”– the finding of a polyp. But one doesn’t anticipate other kinds of surprise…
Doctors in Missouri were baffled to spot a fly inside a man’s intestines during a routine colon screening.
Images taken during the colonoscopy and published in the American Journal of Gastroenterology show the intact fly inside the man’s colon.
Matthew Bechtold, the chief of Gastroenterology at the University of Missouri, told The Independent that he had prodded the fly and confirmed it was dead.
The 63-year-old patient told doctors that he had only consumed clear liquids the day before the procedure and had no idea how the fly had gotten into his colon.
He said he had eaten pizza and lettuce for dinner two days before the procedure but did not remember a fly being in his food.
The finding was described as “a very rare colonoscopy finding and mystery on how the intact fly found its way to the transverse colon.”…
Wonder never cease: “Bizarre Discovery of Intact Housefly in Man’s Intestines Shocks Doctors,” in @ScienceAlert, via @BoingBoing.
* Charles de Lint
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As we investigate intrusive insects, we might spare a thought for Seymour Benzer; he died on this date in 2007. A physicist, molecular biologist, and behavioral geneticist, he developed a method for determining the detailed structure of viral genes, did much to elucidate the nature of genetic anomalies (called nonsense mutations), and identified mutant genes useful for studying Creutzfeld-Jacob (CJ) disease and other human brain degenerative disorders… all using the ubiquitous cousin of the housefly– the fruit fly– as a research subject.
Benzer was awarded the National Medal of Science (in 1982), among many other major awards and recognitions.
“The most outstanding feature of life’s history is a constant domination by bacteria”*…
Jennifer Kahn interviews biochemist Jennifer Doudna (who won the Noel Prize for the gene-editing engine Crispr) on her new focus– our microbiomes, tackling everything from immune disorders and mental illness to climate change—all by altering microbes in the digestive tract…
… what isn’t the microbiome responsible for? It’s been all the rage for the past few years, with scientists hoping it could help treat everything from immune disorders to mental illness. How exactly that will work is something we’re just starting to explore. This spring, the effort got a boost when UC Berkeley biochemist and gene-editing pioneer Jennifer Doudna, who won a Nobel Prize in 2020 for coinventing Crispr, joined the pursuit. Her first order of business, spearheaded by Berkeley’s Innovative Genomics Institute: fine-tuning our microbiome by genetically editing the microbes it contains while they’re still inside us to prevent and treat diseases like childhood asthma. (Full disclosure: I teach at Berkeley.) Oh, she also wants to slow climate change by doing the same thing in cows, which are collectively responsible for a shocking amount of greenhouse gas.
As someone who has written about genetic engineering in the past, I have to admit that my first reaction was: No way. The gut microbiome contains around 4,500 different kinds of bacteria plus untold viruses, and even fungi (so far: in practice we’ve only just started counting) in such massive quantities that it weighs close to half a pound. (Microbes are so tiny that 30 trillion bacteria would weigh roughly 1 ounce. So half a pound is a lot.)
Figuring out which ones are responsible for which ailments is tricky. First you need to know what’s causing the problem: like maybe something is producing too much of a particular inflammatory molecule. Then you have to figure out which microbe—or microbes—is doing that, and also which gene within that microbe. Then, in theory, you can fix it. Not in a petri dish, but in situ—meaning in our fully active, roiling, squishing stomach and intestines while they continue to do all the stuff they usually do.
Until recently, it would have seemed insane—not to mention literally impossible—to edit all the microbes belonging to a species within a vast ecosystem like our gut. And to be fair, Doudna and her collaborator, Jill Banfield, still don’t know quite how it will work. But they think it can be done, and in April, TED’s Audacious Project donated $70 million to support the effort. My own gut feeling (right?) was that this was either brilliant or terrifying, or possibly both at once. Brilliant because it had the potential to head off or treat diseases in an incredibly targeted and noninvasive way. Terrifying because, well, you know … releasing a bunch of inert viruses equipped with gene-editing machinery into the vital ecosystem that is our gut microbiome—what could go wrong? With that in mind, I invited Jennifer Doudna to my house for a chat about the future of microbiome medicine…
Fascinating– and encouraging: “Crispr Pioneer Jennifer Doudna Has the Guts to Take On the Microbiome,” in @WIRED.
(Image above: source)
* Stephen Jay Gould
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As we investigate our intestines, we might spare a thought for Guido Pontecorvo; he died on this date in 1999. A geneticist, he discovered the process of genetic recombination in the common soil fungus Aspergillus— and as a result the parasexual cycle— in what became the model for the genetic studies in many other fungi. This cycle gives rise to genetic reassortment by means other than sexual reproduction; its discovery provided a method of genetically analyzing asexual fungi…. which, as noted above, populate our microbiomes.
“The unexamined life is not worth living”*…
Diana Gitig reports on research that suggests that some of us agree more actively with Socrates than do others– and for a baked-in reason…
People who enroll in genetic studies are genetically predisposed to do so.
According to the Catalogue of Bias, ascertainment bias occurs when a sample being studied is not representative of the target population. This can produce misleading or even false conclusions, and it can be hard to detect since it cannot usually be identified by examining the sample alone. This is why many studies try to use variables other than participation in the study to make sure their samples are as representative as possible.
Studies examining how a particular treatment affects a particular health outcome often try to handle ascertainment bias by adjusting for “covariates,” things like education level or socioeconomic status, that could affect health outcomes independently of the treatment. But Stefania Benonisdottir and Augustine Kong at Oxford’s Big Data Institute have just demonstrated that we can determine if genetic studies are biased using nothing but the genes of the participants.
And they used that technique to show that there’s a genetic contribution that influences the tendency to participate in genetic studies…
People in a genetic database have segments of DNA in common unexpectedly often: “Want to have your genes tested? It might be genetic,” in @arstechnica.
The Benonisdottir and Kong paper, in Nature Genetics, is here.
* Socrates
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As we battle bias, we might send systemic birthday greetings to Sergei Winogradsky; he was born on this date in 1856. A microbiologist, ecologist, and soil scientist, he discovered chemoautotrophy (now better known as known as chemosynthesis) and the the Nitrogen cycle— which is to say that he pioneered the cycle-of-life concept.
“The world is bound in secret knots”*…
Everyone knows what a knot is. But knots have special significance in math and science because their properties can help unlock secrets hidden within topics ranging as widely as the biochemistry of DNA, the synthesis of new materials, and the geometry of three-dimensional spaces. In his podcast, The Joy of Wh(Y), the sensational Steven Strogatz explores the mysteries of knots with his fellow mathematicians Colin Adams and Lisa Piccirillo…
How do mathematicians distinguish different types of knots? How many different kinds of knots are there? And why do mathematicians and scientists care about knots anyway? Turns out, there’s lots of real-world applications for this branch of math, now called knot theory. It started out with the mystery of the chemical elements about 150 years ago, which were, at the time, thought to be different kinds of knots tied in the ether. Nowadays, knot theory is helping us understand how enzymes can disentangle strands of linked DNA. And also, knot theory has potential in basic research to create new kinds of medicines, including some chemotherapy drugs. But in math itself, knot theory is helping mathematicians work out the riddles of higher-dimensional spaces…
The study of knots unites the interests of researchers in fields from molecular biology to theoretical physics: “Untangling Why Knots Are Important,” from @stevenstrogatz in @QuantaMagazine. Listen here; read the transcript here.
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As we take stock of tangles, we might might send nicely-tied birthday greetings to a beneficiary and user of knot theory, Francis Collins; he was born on this date in 1950. A physician and geneticist, he discovered the genes associated with a number of diseases, led the Human Genome Project, and served as the director of the National Institutes of Health.
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