Friday 7 February 2020

SYNTHETIC BIOLOGY AND LIVING MACHINES




“Synthetic biology” is the design and construction of new biological entities that do not exist in the natural world. Imagine a future where synthetic jellyfish roam waterways looking for toxins to destroy, where eco-friendly plastics and fuels are harvested from vats of yeast, where viruses are programmed to be cancer killers, and electronic gadgets repair themselves like living organisms. Welcome to the world of synthetic biology, or ‘synbio’, where possibilities are limited only by the imagination. Its practitioners don’t view life as a mystery but as a machine – one that can be designed to solve a slew of pressing global health, energy and environmental problems.

When we think of robots the picture that comes in our mind is of a moving gadget made of steel, metal, silicone, plastic or other non-biodegradable synthetic materials. But robots today are both living and bio-degradable and are called xenobots. Scientists in the University of Vermont and Tufts have succeeded in building these living robots from stem cells of frog embryo which can join hands and work together much like super-computers and can perish after achieving their task once their pre-loaded nutrients get used up. The Xenobots are named after the species of African frog – Xenopus laevis whose embryonic cells or stem cells were used by researchers. These cells were incubated and joined under microscope by tiny electrodes. The joined cells came together into body forms never seen in nature!

The possibilities of using these xenobots are immense. They can detect toxic contamination in environment, disintegrate polythene and plastic in the oceans and then gather the micro-plastic from ocean and save our marine life. As they are bio-degradable they will disintegrate without a trace without polluting the oceans. They can also be injected in our blood and targeted towards the blocks in our arteries. They can disintegrate these blocks thus reopening our blocked arteries and then disappear as and when programmed to do so by Artificial Intelligence!

These xenobots can be programmed to pick up payload such as a cancer medicine that is to be carried to a specific organ in the body, kill the cancer cells and then get self disintegrated. To target the tumor cells, peptides that can specifically recognize a tumor were expressed on the surfaces of a vector bacteria. So the chemotherapy is targeted to the desired target and normal body cells are spared of its side effects; needless to say, a much lesser dose of the drug is being used.

The immune system plays an important role in cancer and can be harnessed to attack cancer cells. Cell-based therapies focus on immunotherapies, mostly by engineering T cells. T cell receptors are engineered and ‘trained’ to detect cancer epitopes. Chimeric antigen receptors (CARs) are composed of a fragment of an antibody fused to intracellular T cell signaling domains that can activate and trigger proliferation of the cell. A second generation CAR-based therapy is already approved by FDA

Scientists in UC San Diego have genetically engineered mosquitoes and made them resistant to all strains of dengue virus. They designed the antibody “cargo” to be synthetically expressed in female Aedes aegypti mosquitoes which are responsible for spreading dengue. Once this female sucks in blood the antibody is activated and expressed and starts hindering the replication of virus in the mosquito, thus preventing its transmission to humans even if it bites. On pairing with other infected mosquitoes the antibody is spread throughout the mosquito population thus offering them immunity against the virus thereby stopping the spread of dengue!

The rubber industry is all geared up to reduce its carbon footprints. Natural rubber from the sap of rubber trees cannot meet the world’s demands. Currently, synthetic rubber is derived entirely from petrochemical sources. DuPont, together with The Goodyear Tire & Rubber Company, is currently working on the development of a reliable, high-efficiency fermentation-based process for the BioIsoprene™ monomer, and synthetic biology has played an important role in making this undertaking a reality.

Waste management is a big headache in the agriculture sector. The hull is the woody case that protects the soybeans, and it cannot be digested by humans or other monogastric animals, such as pigs. Surfactants are one of the most useful and widely sold classes of chemicals, because they enable the stable blending of chemicals that do not usually remain associated (like oil and water). Today, nearly all surfactants are manufactured from petrochemicals and worldwide production of surfactants from petrochemicals annually emits atmospheric carbon dioxide equivalent to combustion of 3.6 billion gallons of gasoline. To address this problem microorganisms have been developed in the laboratory that convert agricultural waste like soyabean hulls into useful new surfactants that can be of use in personal care products and other formulations. Similarly Yeast is being engineered to produce rose oil as an eco-friendly and sustainable substitute for real roses that perfumers use to make luxury scents.

In some ways, synthetic biology is similar to another approach called "genome editing" because both involve changing an organism's genetic code; however, some people draw a distinction between these two approaches based on how that change is made. In synthetic biology, scientists typically stitch together long stretches of DNA and insert them into an organism's genome. These synthesized pieces of DNA could be genes that are found in other organisms or they could be entirely novel. A microbe could be genetically engineered in the laboratory to detect a particular pathogen and kill it once it is delivered inside the human or animal body. They have tamed the typhoid causing Salmonella, engineered it to retain its ability to enter the body’s immune cells but also to prevent it from causing diseases. Thus they can use the bacteria to deliver a vaccine orally. It enters through the gut lining, is engulfed by immune cells, and then it starts making vaccine.....much like a bioreactor inside the animal/human body. Alongside stemcell research and genome editing Synthetic Biology could offer new insight into synthesizing body parts and repairing dead tissues and organs!

This harnessing of living cells has however raised several ethical questions. What if these xenobots go out of control? Manipulating complex biological systems may be risky and scientists may end up with a Frankenstein. That AI designed these xenobots adds another layer of risk, the possibility of programming them as biological weapons. Iron clad regulations are necessary to keep the individual egos of rogue scientists and ambition of world domination of rogue nations in check.


The ultimate scope of clinical applications for synthetic biology remains to be seen. Today’s application in diagnostics, drug discovery, and tissue engineering should soon grow more extensive and spawn opportunities that are currently unimaginable. Indeed, synthetic biology has the potential to radically change the way clinicians manage disease and to help us live, longer, healthier lives.

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