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100 years from now

Jason Chin

Jason Chin

Sixty years ago, the structure of DNA was unknown. Today we know enough about DNA to reprogram its instructions to produce synthetic molecules and even cells. As we celebrate a century of MRC-funded advances, Jason Chin from the MRC Laboratory of Molecular Biology speculates about where such research might take us in future.

Synthetic biology is a fascinating new area of science. It’s all about thinking how we might be able to change the way biological systems work, to help us understand them more deeply or to get them to do useful things for us which they can’t normally do.

Its potential applications are broad and, frankly, amazing. For example, some scientists are building biological systems that can count every time a cell divides. In the future this might be used as part of a system to trigger the killing of cells in the human body that have divided more times than expected for a normal cell, such as cancer cells. And beyond medical research, synthetic biology approaches are being investigated to do many other things, from making biofuels to mopping up pollution.

My research involves expanding the available repertoire of amino acids, the twenty building blocks that are strung together to make the proteins which carry out many of the processes that keep us alive. We are working on re-engineering the cellular factories that normally make proteins in a cell to get them to make proteins containing entirely new amino acids that are not found in nature.

This may sound esoteric, but it provides a powerful approach for seeing what proteins get up to in a cell, and takes us a step closer to providing new molecules to tackle disease. By introducing new chemical groups into proteins we can track them, rather like with the GPS on our phones, and find out where they go, and which other proteins in the cell they talk to.

Putting new amino acids into proteins has revealed some long-kept secrets about what proteins do in cells. I anticipate that the insights revealed by these approaches will, in due course, provide some of the very basic knowledge to inform the next generation of translational research.

Synthetic biologists are already on the cusp of improving human health through pioneering approaches that allow us to change and improve drugs that are made of proteins — for example antibodies, insulin or growth hormones. Thanks to Sir Gregory Winter’s work here at the LMB in the 1970s to ‘humanise’ mouse antibodies and make them more suitable for use in people, there’s been an explosion in protein therapeutics and several of the world’s top drugs are now antibody therapies. Sooner or later I think that more drugs will be protein therapeutics, and our ability to ‘soup-up’ these proteins with synthetic biology approaches could vastly expand their scope.

For example, a biotech company in San Diego, Ambrx*, is carrying out a clinical trial of a protein therapeutic for growth deficiency incorporating some of these synthetic amino acids, which they hope will make the drug more stable in the blood so that patients need to take less of it than they normally would.

Other scientists are using these synthetic amino acids to attach antibodies to toxic molecules so that they can be specifically targeted to kill cancer cells, leaving healthy cells unharmed. One challenge that many synthetic biologists face is that our ability to make bits of DNA and move them around far exceeds our understanding of what the consequences will be.

But while research necessarily involves exploring unknown territory, it is tightly regulated and scientists take every precaution that they can to make sure the experiments they are doing are safe. As in every day life, everything we do has some element of risk, but the more we learn through research the more we’re able to judge those risks.

Watson and Crick elucidated the double-helix structure of DNA just 60 years ago. If you think back to a time before we understood the molecular basis of heredity, before we could sequence genomes or even really understood that genes are linked with disease, it would have been impossible to imagine today’s world of antibodies or molecular targeted therapeutics.

Synthetic biology research isn’t going to solve all the world’s problems tomorrow and it is important to be clear that the promise of new approaches often takes many years to be realised in full. There was an interval of many years from Fred Sanger’s invention of DNA sequencing to the sequencing of the human genome; from the discovery of methods for creating monoclonal antibodies by Kohler and Milstein to the creation of antibody therapies.

In decades to come I’m optimistic we’ll see progress on understanding the physical basis of what it means to be a sentient, conscious individual, and how life may have arisen from simple molecules.

Jason Chin

*Jason Chin has a financial interest in Ambrx

 

This article was first published in the Centenary edition of Network.

 

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