Gene Drives: Crispr Critters

In these days of gloom and doom, everyone can use some good news that gives us hope for the future.

Suppose we tell you that the world’s scientists may be on the brink of perfecting a treatment that has the potential to cure all of the deadly diseases that afflict the human race and make us all stronger, healthier, faster and smarter. Using this technique, they may be able to eliminate depression, drug addiction and obesity along with cancer, malaria and the heartbreak of psoriasis. They may be able to add 50 years or more to the average life expectancy of a human being.

That would qualify as good news that promises a brighter future, right?

But what it we also tell you that this incredible breakthrough—let’s call it “evolution in a test tube”—comes with a price, hidden in the fine print at the bottom of research papers now being published in the leading scientific journals: we won’t be humans anymore.

During the past two years, the world’s leading genetic scientists quietly have been debating the ethics of combining the gene-editing technique known as Crispr-Cas9 with a more recent breakthrough that would turbocharge its application, something called a gene drive. If you’ve never heard of Crispr-Cas9, you’re going to be hearing a lot about it soon because, in the short term at least, it promises to revolutionize healthcare, the food we eat and just about everything in between. Here’s a Cliff Notes version of how it works:

In the 1980s, researchers noticed that bacteria have small blocks of DNA repeated several times in their genetic structure, with non-repeated spacers of DNA stored in between them. This pattern is an immune system known by the acronym Crispr, which stands for “clustered regularly interspaced short palindromic repeats.” The spacers match pieces of DNA from viral invaders that bacteria (or their ancestors) have faced before. When activated by this threat, the DNA in the spacers converts to RNA (a.k.a. recombinant DNA). A protein called Cas9 latches onto the RNA, forming a structure that will bind to strands of DNA that match the spacer’s sequence. When the matching strand is found, the Cas9 protein opens the double helix and cuts both sides, breaking the strand and disabling the viral DNA. If the bacterium survives an attack by an unfamiliar virus, it can now make and store a new spacer, which can be inherited by future generations.

About five years ago, two female researchers (we’ll give you their bios when they undoubtedly win the Nobel Prize next year) perfected a Crispr-Cas9 technique using synthetic RNA to control the cutting of any piece of DNA they choose (including human DNA). Cells normally begin the process of repairing the cut, but before that happens the scientists now can insert a snippet of different DNA to fill the gap, effectively editing the DNA sequence.

For well over a century, scientists have tweaked the genetic makeup of living things under our control, including pets, farm animals, crops and numerous lab rats. Initially, they accomplished this though breeding of animals and the development of hybrid seeds for plants. The perfection of the Crispr-Cas9 gene-editing method has opened the door to the genetic engineering of humans. Soon after the breakthrough was announced and replicated in labs, the debate began about whether to apply it to the modification of human embryos, giving them traits that could be passed down to their descendants.

But before non-scientists like us could even begin to contemplate the implications of this genetic leap forward, another breakthrough was heralded that exponentially increases the stakes for everyone. It’s called a “gene drive,” and—in the simplest possible terms—it’s a species changer. Just as scientists in recent years figured out how to automate the process of gene sequencing (identifying all of the genes that make up an organism, a process that used to take years and now can be done in weeks or months), they’ve now figured out how to turbocharge the Crispr-Cas9 gene-editing application by encoding it into people.

Gene drives ensure that a particular gene is transmitted to all of an individual’s offspring (rather than a fraction of them, which is the current rate of gene-alteration transmission due to the ability of natural selection to stem the spread of new genes). By encoding the Crispr editing system itself into an organism’s DNA, scientists now believe they can cause a desired edit to reoccur in each generation, “driving” the trait through the wild population. Substitute “person” for “organism” and “the human race” for “wild population” and you’ll catch our drift here.

When the scientists figured out how to construct a gene drive (about two years ago), they initially told us it would give humans the power to alter or perhaps eliminate entire populations of organisms in the world. Putting the most positive spin on the breakthrough, they rounded up the wanted posters for the world’s most villainous diseases and told us they now might have a reliable way to quickly eliminate them by altering the genetic makeup of the species that carry them. Snip a sequence from a mosquito, implant a gene drive and goodbye, malaria or Zika.

But then the spoil-sports in the scientific community started clearing their throats. You know who we’re talking about, the kind of Nervous Nellies who a century ago just had to point out that while splitting the atom was a big deal, it could lead to nuclear weapons as well as nuclear power plants. For the past two years, these Debbie Downers in lab coats have been warning that gene drives applied to humans could alter our entire species in ways that might not be initiated by people with good intentions.

If you’ve managed to navigate through all the tech details we’ve just provided, here’s the bottom line: if gene drives are widely applied to humans, the human race as we know it may not exist in two or three generations. We’ll be replaced with something different, a new species created in a lab. Thinking for more than a few minutes about all of the “enhancements,” good and bad, that potentially may be attempted on the human genome will have you reaching for an aspirin bottle (we went straight to the cabinet where we hide the bourbon from the kiddies).

We wish we could tell you that this development spawned an intense global debate among scientists which resulted in the establishment of an ethical boundary that would prevent the application of gene drives to the alteration of the human species, much like the consensus reached about 20 years ago that breakthroughs in cloning animals should not be tried on people. Unfortunately, it hasn’t worked out that way. With the Crispr-Cas9 editing technique offering the potential of splicing and replacing defective genes that may cause everything from cancer to heart disease (clinical tests on humans already have been authorized), the scientific urge to turbocharge these breakthroughs—and wipe out these diseases in future generations—using gene drives has intensified.

Instead of a global debate not limited to scientists—a conversation that would include ordinary people like us—the National Academies of Sciences, Engineering and Medicine (NAS), a group that provides advisory judgments on new technology for the federal government, was convened last year to help set the policy on gene drives. We’re talking about 16 eggheads sitting in a closed conference room having a quiet discussion about the end of the world as we know it. The committee considered six case studies, including using a gene drive to control mice destroying biodiversity on islands, mosquitoes infecting native Hawaiian birds with malaria, and a weed called Palmer amaranth that has become resistant to herbicides and a scourge for some farmers. The Bill and Melinda Gates Foundation, which helped pay for the NAS report, already has spent $40 million on a gene-drive project aimed at eradicating the species of mosquitoes that spread malaria.

Two months ago, the NAS group decided to endorse continued research on gene drives, concluding that while the technology poses risks, its possible benefits make it “crucial” to pursue. The group also set out a path to conduct what it called “carefully controlled field tests,” overruling the concerns of what some scientists say is the “substantial risk of inadvertent release” into the environment.

Okay, let’s say that in English: these jokers have given the green light to the testing of gene-drive editing on groups of people, test that potentially could spread alterations of the genetic makeup of humans to the entire population of the world.

“The potential to reduce human suffering and ecological damage demands scientific attention. Gene drive is a fascinating area of science that has promise if we can study it appropriately,” declared Elizabeth Heitman, a medical ethicist at Vanderbilt University who chaired the NAS advisory panel. However, she added that there is not yet enough evidence about the unintended consequences of gene drives to justify the release of an organism that has been engineered to carry one.

That would be very reassuring, Liz, if not for the fact that your group’s endorsement is going to open a floodgate of funding and new research initiatives into this genetic breakthrough around the world. So people like Vladimir Putin and the lunatic who runs North Korea also are going to have a say about whether a new “organism”—a person carrying a gene drive encoded into his DNA—is “released” into the global population. Guess we’ll have to keep our eyes peeled for a Russian sprinter running the 100-meter-dash in five seconds at the 2028 Summer Olympics.

Environmental watchdog groups unsuccessfully argue that the advisory report should have recommended that research on gene drives be halted. Jim Thomas, the program director of the ETC Group in Montreal, said the panel did not consider how to prevent commercial and military interests from misusing the technology, which he said should be placed under the control of the United Nations. Kevin Esvelt, a Massachusetts Institute of Technology evolutionary biologist who also has pioneered the technology, said the report failed to address its biggest risk. “They assume you can safely run a contained field trial,” he said. “But anytime you release an organism with a gene drive system into the wild you must assume there is a significant chance that it will spread—globally—and factor that in.”

Most scientists are well-intentioned; they’re usually motivated by the potential good their research may deliver to everyone. But they’ve all got the same defective gene: when they think they can do something new and exciting, they just have to see if it works and openly spread that knowledge to every other scientist on Earth. The unintended consequences come later.

Don’t believe us? Just ask Albert Einstein, whose letter to President Roosevelt convinced FDR to start the Manhattan Project, the result of which Einstein regretted for the rest of his life.

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