The Advantages of Synthetic Viruses

Baric's lab has previously encountered regulatory hurdles regarding their research, which has included engineering novel coronaviruses capable of infecting mice. In 2014, funding from the National Institutes of Health was temporarily halted due to concerns over the safety of such studies, although it was later restored.

In relation to the current outbreak, Baric mentioned that his team ordered the necessary DNA last month. They began by analyzing the virus's genetic sequences, selecting a consensus version for synthesis.

Once the DNA arrives—an event that could take up to a month—Baric intends to introduce these genetic instructions into cells. If successful, the cells should produce infectious viral particles.

By engineering their own viral strains, scientists can access pathogens that may not be obtainable from countries currently facing epidemics. Baric noted that live virus samples from patients in China have not been widely distributed, emphasizing that this approach represents the future of medical research responses to emerging threats.

The synthetic and natural viruses should be nearly identical. However, the synthetic variant allows for repeated genetic manipulation, enabling researchers to identify key attributes such as transmission methods and cellular entry mechanisms. Timothy Sheahan, a researcher at UNC, plans to infect mice with the virus and test various treatments to determine what might inhibit its spread.

Moreover, synthetic viruses can aid in tracking the evolving nature of outbreaks. Stanley Perlman, a microbiologist at the University of Iowa, expressed concern about potential mutations of the virus during the epidemic. He believes that synthetic models will facilitate the study of mutation impacts, allowing for the identification of vulnerabilities and the development of therapeutic options.

Historically, scientists had to wait extended periods for access to the pathogens responsible for outbreaks, but with SARS-CoV-2, its genetic sequence was available online within weeks. This prompted immediate action, with researchers comparing it to viruses found in bats, snakes, and pangolins, leading to insights about its potential origins.

Biotechnology firms, governments, and academic institutions quickly began ordering physical samples of specific genes from the virus. According to Adam Clore, a synthetic biology director at IDT, there has been a significant increase in requests for viral components, particularly those needed for diagnostic tests and vaccine development.

"Since the genome was released, we've seen a remarkable rise in demand," Clore stated. "Many institutions are focusing their efforts on detection and vaccine development."

While most researchers require only a few viral genes for their work, Baric's lab is uniquely positioned as the only known facility in the U.S. attempting to recreate the entire virus from purchased DNA.

Safeguarding Against Biosecurity Threats

In the early 2000s, scientists demonstrated that synthetic DNA could resurrect viruses using their genetic codes. A notable example involved a New York-based team that successfully produced infectious polio material from ordered DNA.

This capability raised alarms regarding biosecurity. The possibility of malicious actors using similar techniques to resurrect smallpox has not materialized, yet the concern remains that viruses like polio and SARS-CoV-2 cannot be completely eradicated. In 2005, researchers at the CDC highlighted this point by resurrecting the 1918 influenza virus, which caused millions of deaths.

To mitigate the risks associated with this technology, DNA manufacturing companies have collaborated to restrict access to hazardous genes. Major U.S. firms have agreed to cross-reference DNA orders with a database of approximately 60 select agents—pathogens and toxins that are strictly monitored by the government.

At our request, Battelle—a scientific research organization—utilized its ThreatSEQ software to simulate a scenario involving an order for SARS-CoV-2. According to Craig Bartling, a senior research scientist at Battelle, the software flagged the entire virus and most of its individual genes at the highest risk level due to its close resemblance to SARS.

Research into the new virus is considered sufficiently risky that DNA manufacturers convened recently to establish guidelines governing who may procure complete genomic sequences of SARS-CoV-2. In a statement issued on February 11, the International Gene Synthesis Consortium expressed a cautious stance, proposing to treat the new virus as if it were SARS—an agent that has been tightly regulated since its addition to the select agent list in 2012.

Consequently, anyone wishing to obtain a complete synthetic version of SARS-CoV-2 would undergo rigorous vetting and must demonstrate prior registration with the CDC for work involving SARS, similar to the North Carolina researchers.

Nonetheless, DNA manufacturers retain discretion over their sales, and not all agree that the full virus genome should be available. Claes Gustaffson, a DNA supplier from Atum in California, noted that while he approved several requests for parts of the viral genome, he would decline orders for the complete virus.

"They probably want to develop a vaccine as quickly as possible," Gustaffson remarked. "However, some viruses, like polio, should never be synthesized, regardless of the requester."

Opinions on the dangers of synthesizing the new coronavirus vary. Nicholas G. Evans, a biothreat researcher at the University of Massachusetts, Lowell, believes that the benefits of understanding the virus outweigh the associated risks. "Currently, many experts are focused on comprehending how this coronavirus functions. The risks appear minimal compared to the potential benefits," he stated.

The outbreak, which likely originated from a live animal market in Wuhan, had resulted in over 64,000 cases and 1,350 deaths in China by February 14—making it more severe than the earlier SARS epidemic, which claimed 774 lives.

Despite the ongoing outbreak, the U.S. has yet to classify the new virus as a select agent. Baric explained that such decisions are typically not made during an outbreak to avoid hindering research efforts.

Addressing Public Concerns

At present, only a select group of advanced laboratories possess the capability to synthesize a virus; the likelihood of an amateur attempting such a feat is virtually non-existent. "We're at a stage where only the most elite labs are capable of synthesizing this new virus concurrently with the outbreak. Fortunately, the number of facilities with this ability is limited," Evans commented.

The rapid advancement of synthetic virus research and the potential for genetic engineering have led to heightened public anxiety and conspiracy theories. Social media and various blogs have circulated unfounded claims suggesting that the new virus was unintentionally released from a Chinese bioweapons lab. While there is no evidence supporting this theory—and considerable evidence against it—the rumor has strained diplomatic relations with China, particularly after being voiced in the U.S. Congress by Senator Tom Cotton.

Baric maintains that synthesizing the new virus poses no particular danger at this stage of the outbreak, especially given that the virus continues to circulate naturally. "Ultimately, whether derived from a living cell or synthesized, the result is the same," Baric concluded.