The Nobel-prize is undoubtedly one of the highest honours a scientist can receive. As synthetic biology is a relatively young field, there is not an overwhelmingly long list of synbio Nobel laureates. Earlier this week, however, George P. Smith, Sir Gregory P. Winter, and Frances H. Arnold, shook hands hands with the King of Sweden and received their gold medals for their pioneering work in synthetic biology (although the prize was technically for chemistry). So, what did these scientists actually do to put synthetic biology onto the Nobel-map?
George Smith and Gregory Winter were presented with the prestigious prize for their work in developing and utilising a method called phage display. Bacteriophages (or phages) are a type of viruses which are only capable of infecting bacteria, and are thus generally harmless to humans. Like any virus, they are very simple organisms, with very simple genomes, which makes them ideal for genetic editing. In phage display, the genomes of the phages are modified to make the phage produce a particular antibody, attaching it to its outer surface, and thus “displaying” it.
What’s so great about having simple viruses put on a display of antibodies?
See, antibodies are generally used in science and medicine because of their ability to bind extremely specifically to certain proteins. In order to find the particular antibody that will bind to your specific protein, you may have to test thousands and thousands of antibodies before you find your match. This is where phage display is useful.
What you can do is have thousands of phages all displaying different antibodies; a library of antibody displaying phages. You can then “dip” your protein into this library, and when you find the antibody that sticks, out of that library you pull not just the antibody, but also the phage attached to it. Since the phage contains the genome necessary for producing this antibody, you can then simply infect a bacteria with this phage, and start up a tiny microbial factory producing your particular antibody.
Why do we need the phage? Well, if we just dipped our protein in random antibodies, we would then need to go through a number of complex tests to try and identify the antibody stuck to our protein. With phage display, that step becomes very simple. George Smith is the man credited with the invention of this whole method. Of course, you can have your phage library express any type of peptide, not just antibodies, and you can test interactions and binding of lots of different peptides for lots of different purposes. For instance, you can test different peptide-inhibitors to see which will bind to and block a certain receptor or enzyme involved in a disease. For example, peptide inhibitors are a large category of cancer treatments. However, it is work with the antibody approach that got Gregory Winter on the Nobel-prize list.
The other half of this year’s Nobel prize in Chemistry went to Francis H Arnold, for something completely different. The Motivation for these three scientists getting lumped in together in receiving the prize is that they all “harnessed the power of evolution”, which can be interpreted as a fancy way of describing synthetic biology. Anyway.
While professors Smith and Winter worked on phage based screening systems for protein interactions, Professor Arnold instead worked with shaping and modifying enzymes to give them new or improved functions. Enzymes are wonderful for chemical synthesis, because while making chemical reactions happen in a lab, one often has to use toxic or expensive catalysts, or extreme temperatures and pressures. Even after that, you might end up with a mixture of different chemicals, not just the particular one you wanted, so you have to spend more money on energy and chemicals for purification. In contrast, enzymes have the ability to highly specifically change one chemical into another, under mostly room temperature and conditions. Thus, enzymes are extremely powerful when it comes to synthesis of things like biofuels or drugs. But though enzymes are very efficient at what they do, there is a limit to what they can do.
For many of the chemical transformations that can be achieved in the lab with expensive catalysts and energy intensive temperatures, there exists no enzyme capable of doing the same. This is where enzyme engineering can save the day.
Professor Arnold has dedicated her life’s-work to studying and developing how to make enzymes do things never seen before in nature. And that’s no small feat. We don’t yet know exactly which part of an enzyme should be changed in order to get it to do what we want. We can’t even predict which changes will be detrimental and result in a completely non-functional enzyme. What we can do, is to make lots of small changes at different sites in the genes of an enzyme, and test which change will direct the enzyme towards having a desired trait. An enzyme engineered for a specific purpose.
The first SynBio Nobel prize?
Synthetic Biology did not really emerge as a field until the 2000s, and gene editing was not even really possible before the 1970’s. As Nobel-prizes go, they are often awarded based on life-long research, so it’s not surprising that synthetic biology is not taking the stage until now. But is this really the first SynBio Nobel prize? That depends on how you want to define SynBio. In 1980, the Nobel prize in chemistry was awarded three scientists (including Frederick Sanger) for the development of the first method for reading DNA-sequences (Sequencing). DNA-sequencing is a cornerstone of synthetic biology, and without it the field would not even exist. But was the method in itself synthetic biology or just molecular biology? The same goes for the 1993 Nobel prize on the development of the PCR method, yet another cornerstone of synthetic biology. Ask any synthetic biologists or biotechnologists, and they’ll tell you PCR is one of the most fundamental and frequently used methods in their lab, allowing you to mass-produce and edit DNA. But is the method in itself Synthetic Biology?
This year’s Nobel prize in chemistry is a testament to the emergence of Synthetic Biology as its own field, and the massive contributions it can make to the scientific world. Will there be more SynBio Nobel prizes in the future? Count on it.
As the CRISPR technology has been the head-tuner of the year as far as biotechnology, and biology in general, goes, there has also been significant speculation as to when rather than if the technology would receive its Nobel prize. Even in anticipation of this year’s (and last years) Nobel Prize announcements, people were betting on CRISPR to take the cake. Not to mention other great achievements in Synthetic Biology like CAR T- cells, the revolutionary immunotherapy that is making previously untreatable cancers treatable.
Regardless of weather you consider this the first ever SynBio Nobel Prize, I think it’s fair to assume that it will not be the last.