From Cloning Monkeypox Genome to Editing Human DNA, Is Synthetic Biology a Double-Edged Sword?

From Cloning Monkeypox Genome to Editing Human DNA, Is Synthetic Biology a Double-Edged Sword?
(Natali_ Mis/Shutterstock)
Xiaoxu Sean Lin
7/26/2022
Updated:
10/17/2022
In the June 2022 issue of Virologica Sinica, researchers at Wuhan Institute of Virology (WIV) published a paper that said WIV efficiently assembled a large fragment of the monkeypox virus genome for the purpose of developing a PCR test for monkeypox.

This WIV article is not particularly eye-catching at the first glance, but it does raise doubts when one thinks about its objective and approaches.

First, the development of a PCR test is a mature and routine practice in molecular biology and does not require a large fragment of the virus as a template or positive control. Secondly, from a biotechnology point of view, to assemble a large virus genome in the lab is no small feat. These two do not add up–why undergo a difficult endeavor in synthetic biology just to accomplish a simple goal?

What Is WIV Really Doing?

In this WIV paper, the researchers knew very well about the biosafety concern, so they explained why they had to make the virus fragment in the lab. “Because MPXV [monkeypox] infection has never been associated with an outbreak in China, the viral genomic material required for qPCR detection is unavailable.”

In other words, since there was no monkeypox in China, they did not have access to the natural virus. So, to develop a PCR test for monkeypox, they had to make a fragment of it in the lab. The researchers further stated that they only made less than one third, or in more technical terms, 55-kb length, of the genomic fragment of monkeypox virus. If the MPXV fragment was used as a template for primers, DNA fragments in several hundreds to 1kb lengths would usually be sufficient. If the fragment is needed for positive control, it does not need to be as long as 55-kb in length. The whole SARS-CoV-2 virus genome is only about 29kb in length.

Note that at the time of WIV’s research, monkeypox outbreaks had long been found in many countries in Africa and around the world. Moreover, the gene sequence of the monkeypox virus already exists. The researchers in WIV could simply use the available sequence to obtain shorter fragments commercially in a very cost-effective and time-saving manner. It is common practice to develop PCR tests without a large virus genome or fragment.

Furthermore, Chinese media reports have already shown that other Chinese companies have successfully developed monkeypox PCR tests with minimum effort.

A report by Beijing Economic Technological Development Area dated May 30, 2022 said that several companies in the area had developed PCR testing kits for monkeypox. One of them is BioChain, whose research only took 17 days, from May 8, when a focused team was formed, to May 24, when the test kit received the European commission CE marking, deeming that it met the safety, health, and environmental protection requirements of the European Union.

The key to the rapid development lies in the company’s Pathogen Molecular Identification Database (PMDB). By comparing the monkeypox virus genome sequences in PMDB against the known monkeypox or orthopoxvirus whole genome sequences, they were able to identify the specific gene sequence of monkeypox virus strains. They were then able to quickly develop the PCR assay within one month.

In addition, Beijing Kinghawk Pharmaceutical Co. Ltd., on May 27 announced a similar test kit, which also received European commission CE marking. The report says the team started the research in mid-May, and that they mostly relied on information in published research papers.

This indicates that designing a PCR test for MPXV is not a daunting task at all.

If these lesser-known companies can accomplish the task, why did WIV choose the difficult and unnecessary route of constructing a large fragment of the virus genome? Maybe the real purpose of WIV assembling the genome was to exercise the new synthetic technology called TAR (Transformation-associated recombination) cloning.

The WIV paper says, “a 55-kb genomic fragment of monkeypox virus encompassing primary detection targets for quantitative PCR was assembled by TAR using pGFCS in VL6-48B.”

Again, being able to assemble a considerable portion of a large monkeypox virus genome by TAR is remarkable. Is this all just for designing a PCR test?

Indeed, the WIV researchers were fully aware of the safety concerns. So they wrote in the paper, since they only cloned “less than one-third of the monkeypox genome,” it is “fail-safe by virtually eliminating any risk of recovering into an infectious virus.”

To paraphrase, since they only made one third of the virus, there is no need to worry about the whole virus being made. Apparently, the peer reviewers were satisfied with this explanation.

It’s worth mentioning that Virologica Sinica is managed by the Chinese Society for Microbiology, and the infamous “bat-woman” Shi Zhengli from WIV is the editor-in-chief.

Synthetic Biology

Synthetic biology has been developing rapidly in the past decade. The first synthetic bacterial cell was constructed in 2010 by Dr. Daniel Gibson at the J. Craig Venter Institute in San Diego, California. Since then, an enabling suite of DNA synthesis and assembly methods has been developed.

In recent years, synthetic biology has found applications in biosensing, therapeutics, and the production of biofuels, pharmaceuticals, and novel biomaterials. All these possibilities made synthetic biology platforms powerful, promising, and dangerous at the same time.

Like a double-edged sword, if this technology falls into the hands of people with no moral baseline and a history of unethical practices, it could spell trouble.

Genome-edited Babies

In 2018, Chinese scientist He Jiankui invoked bioethical controversy when he announced that he had created the first genetically edited human babies. He Jiankui was working at the Southern University of Science and Technology in Shenzhen, China, at the time.

He used CRISPR gene editing (CRISPR/Cas9) technology to modify the DNA of the embryos’ genomes. In November 2018, He announced the birth of genome-edited twin girls via Youtube videos. It is said that a third baby was born in 2019. The experiment was conducted in secrecy at the beginning with consenting parents, some reports say.

An editor for biomedicine of the MIT Technology Review exposed the secret project based on He Jiankui’s applications for conducting a clinical trial on the Chinese clinical trials registry. This could indicate that the Chinese authorities and the university He Jiankui worked at knew about the project.

Moreover, after the twin girls were born, Chinese state media People’s Daily praised it as “a historical breakthrough in the application of gene editing technology for disease prevention.”

Some news reports claim that three Chinese state institutions were listed as the funders of He’s experiment: the Ministry of Science and Technology (the nation’s federal science agency), the Shenzhen Science and Technology Innovation Commission, and Southern University of Science and Technology, where He was a professor.

As the international community started to criticize the controversy, Southern University of Science and Technology said they were not aware of the project. The Chinese Communist Party (CCP) investigated and found that He Jiankui and two colleagues acted alone in this secret experiment.

On December 30, 2019, He Jiankui and two collaborators were found guilty of having “forged ethical review documents and misled doctors into unknowingly implanting gene-edited embryos into two women,” effectively clearing any alleged involvement of the CCP. He Jiankui was sentenced to three years in prison, and was released in April 2022.

Michael W. Deem, an American bioengineering professor at Rice University, was He’s doctoral advisor, and was investigated by Rice University. No results have been announced.

Stanford University also investigated its faculty William Hurlbut, Matthew Porteus, and Stephen Quake, who were He’s main mentors in gene editing. The investigation concluded that they “had no research, financial or organizational ties to this research.”

Finally, the controversy was settled as He and two other people were sent to prison. No other entities or individuals were involved. Case closed. Really?

Concerning Ambiguity

Through these cases, the ambiguity in ethics concerning synthetic biology is clear.

It is also concerning that no internationally recognized regulations to ensure biosafety in the field of synthetic biology exist today.

As the United States provides the most favorable conditions for the advanced technology to be developed, it is equally important for the United States to be the leader in setting the regulations. So, how is it being done?

Cooperating With China

One high profile event on biosafety is particularly puzzling.
In July 2019, Johns Hopkins University and Tianjin University (Tianjin, China) co-hosted a meeting in Washington D.C., titled “Biosafety and Biosecurity in the Era of Synthetic Biology: Perspectives from the United States and China.”

Why Johns Hopkins, a world-renowned institution, would join efforts with the Center for Biosafety Research and Strategy at Tianjin University is beyond explanation.

On its website, Center for Biosafety Research and Strategy at Tianjin University says that it was

founded in September 2016 under China’s Ministry of Education, and in response to CCP secretary Xi Jinping’s order to “strengthen the nation’s capability in biosafety.”

The director of the Center was part of the CCP’s Thousand Talents program, which has lured tens of thousands of overseas scientists to bring the latest advances in their respective fields of expertise to China in a clandestine way.

The one-day meeting generated a report (PDF) which includes nothing substantial. The meeting participants agreed that “biotechnology has the potential to have a positive impact on international economies, sustainability, human health, and security. However, the current international governance structure for biological sciences is ill-equipped to manage risks from emerging biological technologies while still promoting beneficial research and development. Improved governance will require increased investment and a concerted global effort to create norms that support biosafety and security.”

Albert Einstein once said, “The human spirit must prevail over technology.” Einstein seems to have prophesied the modern technological advancement. Indeed, synthetic biology is undoubtedly one of the greatest technological accomplishments in recent human history. Yet, without the clear conscience and human morality, it can be disastrous to humanity.

Xiaoxu Sean Lin is an assistant professor in the Biomedical Science Department at Feitian College in Middletown, New York. He is also a frequent analyst and commentator for Epoch Media Group, VOA, and RFA. He is a veteran who served as a U.S. Army microbiologist and also a member of Committee on the Present Danger: China.
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