Foreign Policy: The genetic engineering genie is out of the bottle
Usually good for a conspiracy theory or two, U.S. President Donald Trump has suggested that the virus causing COVID-19 was either intentionally engineered or resulted from a lab accident at the Wuhan Institute of Virology in China. Its release could conceivably have involved an accident, but the pathogen isn’t the mishmash of known viruses that one would expect from something designed in a lab, as a research report in Nature Medicine conclusively lays out. “If someone were seeking to engineer a new coronavirus as a pathogen, they would have constructed it from the backbone of a virus known to cause illness,” the researchers said.
But if genetic engineering wasn’t behind this pandemic, it could very well unleash the next one. With COVID-19 bringing Western economies to their knees, all the world’s dictators now know that pathogens can be as destructive as nuclear missiles. What’s even more worrying is that it no longer takes a sprawling government lab to engineer a virus. Thanks to a technological revolution in genetic engineering, all the tools needed to create a virus have become so cheap, simple, and readily available that any rogue scientist or college-age biohacker can use them, creating an even greater threat. Experiments that could once only have been carried out behind the protected walls of government and corporate labs can now practically be done on the kitchen table with equipment found on Amazon. Genetic engineering—with all its potential for good and bad—has become democratized.
To design a virus, a bio researcher’s first step is to obtain the genetic information of an existing pathogen—such as one of the coronaviruses that cause the common cold—which could then be altered to create something more dangerous. In the 1970s, the first genetic sequencing of a bacteriophage took weeks of effort and cost millions of dollars just to determine its 5,386 nucleotides, the building blocks of genetic information. Today, sequencing the 3,000,000,000 base pairs that make up the human genome, which dictates the construction and maintenance of a human being, can be done in a few hours for about $1000 in the United States. Xun Xu, the CEO of Chinese genomics research company BGI Group, told me by email that he expects to offer full human-genome sequencing in supermarkets and online for about $290 by the end of this year.
The next step in engineering a virus is to modify the genome of the existing pathogen to change its effects. One technology in particular makes it almost as easy to engineer life forms as it is to edit Microsoft Word documents. CRISPR gene editing, developed only a few years ago, deploys the same natural mechanism that bacteria use to trim pieces of genetic information from one genome and insert it into another. This mechanism, which bacteria developed over millennia to defend themselves from viruses, has been turned into a cheap, simple, and fast way to edit the DNA of any organism in the lab.
If experimenting with DNA once required years of experience, sophisticated labs, and millions of dollars, CRISPR has changed all that. To set up a CRISPR editing capability, the experimenter need only order a fragment of RNA and purchase off-the-shelf chemicals and enzymes, costing only a few dollars, on the Internet. Because it’s so cheap and easy to use, thousands of scientists all over the world are experimenting with CRISPR-based gene editing projects. Very little of this research is limited by regulations, largely because regulators don’t yet understand what has suddenly become possible.
China, with its emphasis on technological progress ahead of safety and ethics, has made the most astonishing breakthroughs. In 2014, Chinese scientists announced they had successfully produced monkeys that had been genetically modified at the embryonic stage. In April 2015, another group of researchers in China detailed the first ever-effort to edit the genes of a human embryo. While the attempt failed, it shocked the world: This wasn’t supposed to happen so soon.
In April 2016, yet another group of Chinese researchers reported having succeeded in modifying the genome of a human embryo in an effort to make it resistant to HIV infection, though the embryo was not brought to term. But then, in November 2018, Chinese researcher He Jiankui announced that he had created the first “CRISPR babies”—healthy infants whose genomes were edited before they were born. The People’s Daily gushed over the “historical breakthrough,” but after a global uproar, the Chinese authorities—who, He claims, had supported his efforts—arrested and later sentenced him to three years in prison for unethical conduct. But the Rubicon of biomedical science had been crossed.
China’s legion of rogue scientists is certainly a worry. But gene-editing technology has become so accessible that we could conceivably see teenagers experimenting with viruses. In the United States, anyone who wants to start modifying the genome in their garage can order a do-it-yourself CRISPR kit online for $169, for example. This comes with “everything you need to make precision genome edits in bacteria at home.” For $349, the same company is also offering a human engineering kit, which comes with embryonic kidney cells from a tissue culture originally taken from an aborted female human fetus. Shipment is advertised to take no longer than three days—no special couriers or ice packs needed.
Mail-order DNA fragments enabled a team at the University of Alberta, in 2017, to resurrect an extinct relative of the smallpox virus, horsepox, from scratch by stitching together the fragments. Horsepox is not known to harm humans, but experts warned that the same method could be used by scientists without much specialized knowledge to recreate smallpox—a horrific virus finally eradicated in 1980—within six months at a cost of about $100,000. Had the Canadian scientists used CRISPR, their cost would have been reduced to a fraction.
In my book, The Driver in the Driverless Car, published before the Canadian horsepox resurrection and the Chinese gene-edited babies, I warned about the dangers of gene editing, predicting we would have to make difficult choices about whether to restrict synthetic biology technologies. When used for good purposes, these technologies can help solve the problems of humanity—by quickly finding cures for diseases, for example. When used for evil, they can wreak global havoc of exactly the kind we are now fighting. That is why many people, myself included, have advocated for a moratorium on human gene editing.
But not just a moratorium: There should have been international treaties to prevent the use of CRISPR for gene editing on humans or animals. The U.S. Food and Drug Administration should have kept companies from selling DIY gene-editing kits. Governments should have placed restrictions on labs such as the University of Alberta’s. But none of this happened, nor were there any other checks and balances. It is now too late to stop the global spread of these technologies—the genie is out of the bottle.
Now, the only solution is to accelerate the good side of these technologies while building our defenses. As we are seeing with the development of vaccines for COVID-19, this is possible. In the past, vaccines took decades to create. Now, we are on track to have them within months, thanks to advances in genetic engineering. The Moderna Therapeutics and Pfizer/BioNTech vaccines, which are now in third-stage clinical trials, took only weeks to develop. It is conceivable that this could be reduced to hours once the technologies are perfected.
We can also accelerate the process of testing vaccines and treatments, which has become the slowest part of the development cycle. To test greater numbers of potential cancer drugs more quickly, for example, labs all over the world are creating three-dimensional cell cultures called “patient-derived organoids” from tumor biopsies. The leading company in this field, SEngine Precision Medicine, is able to test more than 100 drugs on these organoids, removing the need to use human subjects as the guinea pigs. Researchers at Harvard University’s Wyss Institute announced in January 2020 that they had developed the first human “organ-on-a-chip” model of the lung that accurately replicates a human organ’s physiology and pathophysiology. Engineers at the Massachusetts Institute of Technology have been developing a microfluidic platform that connects engineered tissues from up to 10 organs, allowing the replication of human-organ interactions for weeks at a time in order to measure the effects of drugs on different parts of the body. Many more such systems are being developed that could accelerate testing and treatment. All these technologies will greatly strengthen our biodefense.
There really is no turning back to correct the mistakes of the past. The genie cannot be put back in the bottle. We must treat the coronavirus pandemic as a full dress rehearsal of what is to come—unfortunately, that includes not only viruses that erupt from nature, but also those that will be deliberately engineered by humans. We must learn very quickly to build the same types of types of defenses that our computers have against their invaders. The good that might ultimately come from this is the cure for all disease. The bad is just about too terrible to think about.