Synthetic biology and biosecurity

Vincenzo Natali’s spine-tingling thriller Splice explores the ethical and scientific conundrums of synthetic biology where two rock-star scientists create a new synthetic life form by combining DNA from two different organisms. Just three weeks before the release of the film on May 20, 2010, Craig Venter at the J. Craig Venter Institute, Maryland, USA announced the creation of the first synthetic bacterium, called Mycoplasma mycoides whose genome they synthesised entirely in the lab.

This was the first self-replicating cell on the planet whose parents came from a computer. But unlike “Frankenstein,” Vincenzo Natali’s could concurrently for the first time depict the same technological breakthrough which had taken place at Venter’s lab in his movie. Man had suddenly started playing God by creating life while science-fiction like never before was simultaneously turning into reality.

While Venter’s team took ten years and $40 million to make a carbon copy of the genome, a small group of scientists at ETH (German: Eidgenössische Technische Hochschule) Zurich in April 2019 developed a technology which modified a genome using computers within the time frame of one year at 120,000 Swiss francs which is a fraction of the cost of the previous experiment.

They could achieve this in the Caulobacter genome, by synthesising 236 genome segments and inserting them into the bacterial genome after joining them together, a process which replaced about one-sixth of the genome. By doing so, the researchers demonstrated the ability to produce strains of bacteria that contained both the naturally occurring Caulobacter genome and also segments of the new artificial genome.

By turning off specific natural genes in these bacteria, scientists could test the functions of the synthetic genes. They tested each one of the artificial genes in a multi-step process. In these experiments the researchers found that about 580 of the 680 artificial genes were functional. With this experiment, they could demonstrate that it was possible to produce functional bacterial cells with such genomic modifications. They had performed this experiment with two objectives in their minds, first to create genomes easily, and second to address fundamental questions in biology.

Researchers at the Medical Research Council Laboratory of Molecular Biology in Britain were similarly able to rewrite the DNA of the bacteria Escherichia coli and configure a synthetic genome four times larger and way more complicated than any previously created.

Such developments have great potential for the growth of synthetic organisms that have the capability of producing a wide variety of products such as DNA vaccines and other life-saving molecules. On the negative side, we could also use this technology for making bio-weapons.

Synthetic biology is a new interdisciplinary area that involves the application of engineering principles to biology. Synthetic biology combines the chemical synthesis of DNA with growing knowledge of genomics. It enables researchers to create catalogued DNA sequences and assemble them into new genomes. The recombinant DNA or genetic engineering that developed in the 1970s differs from synthetic biology as it was based it on the central dogma of life which supposed that a stretch of DNA produced an RNA which in turn produces a protein.

This technology scored several successes, such as cloning of the insulin gene into a bacterial genome for manufacture of biosynthetic insulin. It also helped develop several transgenic plants and animals that came to be described as GMOs or genetically modified organisms. However, the technology had several shortcomings. It was expensive and messy.

Synthetic biology makes it possible for anyone to create any DNA. Gene companies and amateurs today can today type any sequence of DNA into an Internet order form and in a week or two have the DNA arrive by mail.

With the new technology and substantial funding, many start-ups are taking this world beyond the realm of science fiction by creating products such as cow free milk, animal-free meat, changing the colour of the blooms and leaves in a plant, producing glowing plants and detecting diseases from a drop of blood. A start-up called “Cambrian Genomics” started by Austen Heinz with its vision to democratise creation has frightened bioethicists as it is helping customers tinker with genetic codes of plants and animals and even design new creatures.

Anyone in the world today with a few dollars can create a new organism. Scientists at “MRC lab of Molecular Biology” also have further widened the scope of finding extraterrestrial life forms on other planets which are based on different biochemistry to that found on earth. Synthetic Biology can revolutionise several fields; it can improve agriculture by modifying crops to grow faster and healthier. We could also use it to diagnose and monitor diseases in humans and animal
s and develop new drugs and vaccines that would be more effective.

A cure for cancer could lie within Synthetic Biology. Synthetic Biology can also help find alternatives to fuels such as the bio-fuels.

On the other side, the emerging technology of synthetic biology has raised the spectre of new generation bio-weapons. Rapid advances in technology now mean that scientists can create dangerous viruses, make pathogenic and contagious microorganisms more sinister, and change harmless non-pathogenic forms to highly virulent forms which release toxins upon entering the body.

The US National Academy of Sciences, at the request of the Department of Defence, has picked the aforesaid three scenarios as the threats of the highest concern.

Michigan Medical School and chair of the committee has identified three concerns of highest priority which includes the re-creation of pathogenic viruses such as Ebola, SARS, or smallpox, including the transformation of harmless bacteria into virulent ones. On July 11, 2002, Professor Eckard Wimmer at the State University of New York, Stony Brook, USA using mail order DNA and referencing an online genetic sequence of the virus, synthesised the polio virus, which had been eradicated in the US in 1979. It was the first time they were creating a virus from a scratch with synthetic DNA.

The Pentagon funded the work partly to establish whether terrorists could execute such a feat. Fast forward to 2016, virologist David Evans at the University of Alberta in Canada could engineer the once extinct horse pox virus and also made it accessible to the public by publishing his research.

The success of such experiments raises the possibility of sci-fi kind of bio-warfare and also the possibility of bio-terrorists creating the deadly smallpox virus and letting it loose to wipe out human populations.

Nearly 40 years ago, we eradicated smallpox after giving vaccines to millions in Africa, Asia, and South America. During the Cold War, the authorities handed the last two smallpox vials in the custody of Centers for Disease Control and Prevention in Atlanta, USA and at the State Research Center of Virology and Biotechnology in Siberia, USSR for future study purposes. 

In 2017, The Siberian Times reported that professor Ilya Drozdov, the 63-year-old microbiologist who headed the state research facility and where Russia’s smallpox sample was in a secret storage had vanished from his hometown of Saratov in southwestern Russia. No further information was forthcoming after this report.

On May 15, 2018, the Johns Hopkins Center for Health Security conducted a table-top exercise envisaging a scenario in which experts in pandemic response and national security came to grips with a fictional virus created by a terrorist group called “Clade X” to depopulate the earth by deliberately releasing the contagious virus in different parts of their world. “Clade X” had deadly genes of Nipah virus cloned into a mild human parainfluenza virus. The experiment, disclosed that the pandemic resulting from the release had caused simulated deaths of 900 million people within a year as authorities struggled to contain the social and economic chaos until they could make a vaccine.

This exercise showed that synthetic organisms could cause an epidemic or a pandemic for which we are not prepared or are preparing for. It also showed that we could also use the same synthetic biology tools which the terrorists used to cause harm to fight the disease by deploying the technology for rapid creation of better medicines, va ccines, and diagnostics.

Besides the threats, SynBio can also help save lives. About 110 explosive devices such as landmines remain buried in 70 countries and 15,000 to 20,000 people die each year from accidents with land mines or unexploded bombs. There is a humanitarian need to detect and destroy buried land mines. Bacteria respond to their environments with membrane-bound sensors that interact with intracellular response regulators to control gene expression.

Using synthetic biology new sensors are being built in to identify new chemicals in the environment. Researchers in Israel have developed a bacterium that reacts to explosives in soil by producing a green fluorescent protein. Although, the fluorescence is not visible to the naked eye, a laser in a scanning device detects it and informs it to a computer enabling deactivation of the land mine from a safe distance.

Synthetic biology is a widely misconstrued field where the authorities are grossly underestimating its national security consequences. Synthetic biology has potential for developing biological weapons, and possible unforeseen negative impact on human health and environment. Although right now there are no imminent synthetic biology threats, but to overcome the scenario of falling behind, we must remain ready to address the projected consequences that synthetic biology presents. This domain will soon become an area of concern.

Therefore, regulation, policy legislation and framing guidelines on genetic manipulation could help in sidestepping security issues arising from SynBio. The applications of this technology demand a profound discussion in society about the purposes for which we can use this technology and how we can prevent the abuses.

(Dr Jayanth K. Murali IPS, is ADGP (Law and Order) Tamil Nadu. He can be contacted at www.jayanthmurali.com)