A Crack In Creation: A Nobel Prize Winner's Insight into the Future of Genetic Engineering
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farmaceutical
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whole organs for xenotransplantation
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new individual is added to the national transplant list every ten minutes
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twenty-two people a day die while waiting for a transplant
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As the CEO of one prominent company in this field has stated, the goal is to provide “an unlimited supply of transplantable organs,” organs that can be produced on a made-to-order basis.
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Tens of millions of dollars have been committed to future research, and a company called Revivicor has already outlined plans to breed a thousand pigs a year in state-of-the-art facilities with surgical theaters and helipads to deliver fresh organs whenever they’re needed.
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micropig.
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What is breeding but another tool of genetic manipulation, like CRISPR, only less predictable and efficient?
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extensive inbreeding of dogs has had devastating health consequences.
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With easy-to-use gene editing, it surely won’t be long before consumers can order off-the-shelf enhancements to any dog breed. Where else will our imaginations take us?
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Researchers at UC Berkeley used CRISPR to generate a bizarre array of bodily transformations in crustaceans—gills growing where they shouldn’t be, claws becoming legs, jaws turning into antennae, and swimming limbs becoming walking limbs.
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mythical creatures
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de-extinction.
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In 2015, working with elephant cells, Church’s team used CRISPR to convert the elephant variant to the woolly mammoth variant for fourteen of those genes,
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Even if it could be done, would the resulting animal, birthed by an elephant and lacking its original environment and social culture, really be a woolly mammoth? Or would it simply be an elephant with new traits inspired by woolly mammoth genetics?
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If we’ve driven a species to extinction and we now have the power to bring it back, do we have a duty to do so?
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Long Now Foundation, thinks so; its mission is to “enhance biodiversity through the genetic rescue of endangered and extinct species”
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de-extinct species could badly disrupt ecosystems they’re released into.
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And on a more basic level, if we can avoid altering nature more than we already have, shouldn’t we try to do so?
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more dangerous
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revolutionary technology known as a gene drive, so called because it gives bioengineers a way to “drive” new genes—along with their associated traits—into wild populations at unprecedented speeds, a kind of unstoppable, cascading chain reaction.
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certain DNA sequences, called selfish genes, that can increase their frequency in the genome with each generation, even without conferring any fitness advantage on the offspring.
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selfish genes
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ensure that offspring would have a 100 percent probability of inheriting ...
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There is one major difference with a gene drive, however: part of the new DNA added in contains the genetic information that encodes CRISPR itself.
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mosquitoes.
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new gene drive spread a gene that gave the offspring resistance to Plasmodium falciparum, the parasite responsible for hundreds of millions of malaria infections
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created highly transmissive CRISPR gene drives that spread genes for female sterility.
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cull entire populations by hindering reproduction.
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This thoroughness is what makes gene drives so powerful—and so alarming.
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had a fruit fly escaped the San Diego lab during the first gene drive experiments, it would have spread genes encoding CRISPR, along with the yellow-body trait, to between 20 and 50 percent of all fruit flies worldwide.
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extensive containment
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strategies that could theoretically inactivate gene drives that run amok.
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reversal drive,
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There’s also no way to guarantee that this incredibly powerful tool won’t wind up in the hands of people who have no compunction about using gene drives to cause harm—and
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who may, indeed, be attracted to them for exactly that purpose.
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“Clearly, the technology described here is not to be used lightly. Given the suffering caused by some species, neither is it obviously one to be ignored.”
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reversing the genetic causes of herbicide and pesticide resistance that have evolved
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eradicating, invasive species
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stamping out infectious diseases such as...
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target the mosquito.
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some lucky people are naturally resistant to HIV. These individuals lack thirty-two letters of DNA in the gene for a protein called CCR5, which is located on the surface of white blood cells—those cells that form the bedrock of the body’s immune system.
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in vivo gene-editing therapies,
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Physicians must figure out how to get CRISPR into the tissues that are most affected by a given disease. In addition, this must be accomplished without provoking an immune response in the patients’ bodies. Furthermore, Cas9 and its RNA guide will have to be stable enough to survive inside the body until editing is completed.
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favorite delivery vehicles: viruses.
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an innocuous human virus known as adeno-associated virus (AAV). AAV provokes only a mild immune response and is not known to cause any human disease.
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Duchenne muscular dystrophy (DMD)
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DMD gene—the largest human gene known—which encodes a protein called dystrophin. This protein helps muscle cells contract,
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Males are disproportionately affected; since the DMD gene is found on the X chromosome and males possess only one X chromosome
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researchers are exploring the use of lipid nanoparticles to ferry CRISPR throughout the body. Resistant to degradation and easy to manufacture, these delivery vehicles also have the benefit of releasing the Cas9 protein and its guide RNA into the patient’s body in a regimented way. Viruses (and their CRISPR cargo) can persist in cells for a long time, which—as I’ll explain—can cause problems in the editing process, but lipid nanoparticles deliver CRISPR so that it acts quickly before being broken down by the natural recycling factories of the cell.