June 29, 2020Quiz
Viral 1) _____ are a fundamental tool in research. Production of viral vectors usually entail rendering an infectious virus to be replication incompetent or attenuated. This reduces the risks of working with these agents. Later generation viral vector systems are generally safer than early generation systems. Biomedical researchers are now busy finding ways to squash the new coronavirus. Meanwhile, synthetic biologists are busy 2) _____ it.
In February, a team from the University of Bern published a relatively simple recipe to artificially cook up SARS-CoV-2, the virus that causes Covid-19, in the lab. It required only two main ingredients: synthetic chunks of the virus's genomic instructions, which can be ordered online; and yeast. The manuscript was initially uploaded to the preprint server bioRXiv and now peer-reviewed and published in Nature. If further verified, it means that certified labs can clone whole samples of the coronavirus in a week at roughly $30,000. By democratizing access to the new virus, more labs can work on diagnostic tests, drugs, and vaccines, potentially saving millions of people faster than expected. Yet, in a nightmare scenario, the same technology that could rid us of the plague could also turn it into a 3) _____. These concerns often form the basis of conspiracy theories. But they are not pure fantasy. Back in 2014, federal scientists discovered half a dozen vials of smallpox virus, which most Americans born after 1972 do not have immunity against, while cleaning out storage facilities at the National Institutes of Health. Multiple influenza strains have been made more contagious using synthetic biology, based on testing in 4) _____. Although there has not yet been a synthetic viral Chernobyl, scientists are legitimately concerned about a lab-made or lab-leaked viral strain that could wreak havoc.
The Synthetic Virus Cookbook: To Beat a Virus, First know Your Foe.
The easiest way to get a hold of a virus is by obtaining infected biological tissue, which was difficult at the beginning of the pandemic. The second route is to try to grow the virus inside immortalized cells - in SARS-CoV-2's case, lung cells - but it's like manufacturing cars that blow up the factory and themselves halfway through construction. That leaves the third route: making the virus from scratch. Thanks to advances in synthetic biology and genome engineering, making entire virus genomes in bacteria or yeast hosts has become cheaper, easier, and faster. One recent paper for engineering SARS-CoV-2 used 5) _____ as the viral factory. However, the choice now may be the yeast route. The reason is that coronaviruses have extraordinarily large genomes, which makes it difficult for bacteria to cope with. Yeast, in contrast, is far more pliable. What is more, yeast also has a special power to automatically glue chunks of external 6) _____ material together into a full genome sequence. That is huge: rather than synthesizing the entire coronavirus genome through chemistry, it is possible to do it in chunks to reduce costs, and the yeast will magically assemble the pieces together like a puzzle. The project kicked off in January, soon after Chinese researchers released the virus's genomic blueprint. The team split the genome into 14 manageable chunks, each with slightly overlapping sequences, and ordered synthetic DNA that corresponded to those viral genome bits from a commercial company. Three weeks later, after receiving the fragments in the mail, the DNA, which together represent the entire SARS-CoV-2 genome, was inserted into yeast. Just two days later, the team was able to check the yeast, now blossomed into dot-like colonies on a plate, for signs of the virus's genome. Finally, the virus's genetic material was extracted from the yeast in DNA form and transformed it into RNA. This is like translating one language to another, which the virus naturally uses to multiply. In less than a week, the team was able to generate a fully synthetic virus, one relatively new to humans, and use it to infect sacrificial cells in a dish to study. As a proof-of-concept to the platform's power, the team also made a glow-in-the-dark version of the virus, which can help screen for anti-viral drugs. (If the drugs work, this rave version of the virus should lose its glow.)
The Biosafety Dilemma
Thiel's platform for engineering 7) _____ stands out in its speed and simplicity. Speed in an outbreak is essential, not just for containment but also for research. The new platform is a starting point for labs to easily change the coronavirus's genome, seeing what prevents it from replication or what genomic sequences make it weaker or even unable to infect humans. The beauty is that the system only requires the yeast to reassemble the virus's genome one single time. It is extremely easy to collect more coronavirus by reusing ready-made virus-producing yeast cells, like brewing 8) _____. Yet these selling points are exactly what worries bioethicists. The problem is that by publishing the technology roadmap, it is possible for both scientists and the bd guys to apply the same technique to synthesize more complex viruses, or develop a ?super virus' with high infectivity, virulence or vaccine-resistance.
Whether 9) ____ viruses will ultimately help quash the current 10) _____ is anyone's guess. However, the use of cloned deadly viruses is increasingly championed as a way to battle outbreaks, whether we are comfortable and ready or not.
ANSWERS: 1) vectors; 2) cloning; 3) bioweapon; 4) ferrets; 5) bacteria; 6) DNA; 7) SARS-CoV-2; 8) beer; 9) cloned; 10) pandemic