COVID-19 - Components to the solution

Professor Richard Kitney discusses vaccines, effective testing for antigens and antibodies, effective diagnosis of the various stages of the disease and apps to monitor the population

SynbiTECH 2020, 26-27th October, QEII Centre, London

It remains a strange time for us all. Certainly, in the UK we are currently locked down and this has been extended until 7th May. The UK Government publish the death statistics for the coronavirus on a daily basis - currently sitting at around 800 per day. Having looked at the statistics and extrapolating, it seems as if it’s going to take the UK until the mid to end May to get the deaths below 100 per day. That should trigger a phased response in terms of the relaxation of the lockdown. Whilst a lot of work is ongoing, it is deeply frustrating that at the moment we not to be able to do wet lab work.

My experience is that the days are fully taken up with working online. However, because we cannot go out, except for short walks, it is possible to read more. One of the things I’ve been reading (rereading) is Richard Westfall’s excellent biography of Isaac Newton. Westfall describes how Newton retreated to his uncle’s farm, Woolsthorpe Manor, near Grantham in Lincolnshire, during the plague year of 1666 - when the University of Cambridge was closed. During that year he performed many of his famous experiments on optics and light and formulated his Law of Universal Gravitation. What is striking is that there are certain similarities today. During the plague years of 1665 and 1666 over 30,000 people died in London, and, yet as evidenced by Newton, scientific discovery continued. Coronavirus deaths in London are currently approaching 4000, and there is unprecedented international scientific activity to overcome the coronavirus crisis.

It is now clear that there are several components to the solution. Amongst these are medication for treatment, vaccines, effective testing for antigens and antibodies, effective diagnosis of the various stages of the disease and apps to monitor the population. In relation to vaccines, there are several promising developments. For example, the work of Prof. Sarah Gilbert at Oxford University, who is hoping to have a vaccine in initial human clinical trials this week or next week – with the possibility of producing the vaccine, in quantity, in the autumn of this year. Prof. Robert Shattock at Imperial College, who is developing an RNA-based vaccine that could be ready by the end of the year. And, Moderna, the Boston-based biotech company, has a COVID-19 vaccine that entered clinical trials in mid-March. In all of these cases establishing safety and efficacy will be very important. Once a vaccine(s) has been successfully trialled, the next major problem is producing the vaccine in sufficient quantity.

In previous blogs I have talked about the Canadian company, Medicago, that is using methodology based on tobacco plants to produce vaccines. In an interesting, recent article in the Wall Street Journal, Saabira Chaudhuri and Denise Roland also described how British American Tobacco (BAT) is taking strategically similar approach to Medicago at their Kentucky bioprocessing subsidiary. As these authors point out, BAT, for example, has a great deal of expertise in growing tobacco, which is cheap to grow and, because it is agriculturally based, has the potential to produce large amounts of the vaccine rapidly. Certainly, in the case of Medicago, their methodology is based in synthetic body (where the use of robotics and automation will greatly increase reliability and reproducibility).

So, what about effective testing for antigens and antibodies and can synthetic biology (engineering biology) play an important role? At the heart of the synthetic biology approach is DNA (RNA) sequencing and synthesis, which are certainly important in certain approaches to vaccine development - for example that of Robin Shattuck. However, in addition, the whole Design, Build, Tests and Learn (DBTL) approach of synthetic biology lends itself directly to systematic BioDesign and computer-based workflows. This, in turn, has led to the much wider use of laboratory automation and the development of Biofoundries. In relation to testing for coronavirus antigens, it can be argued that testing using human operatives can be slow, potentially unreliable and subject to error. Whereas, the advantage of synthetic biology based automated testing is that it has the potential to be much more reliable. One interesting example is the work being carried out in our centre, SynbiCITE, at Imperial College London. This is being led by my immediate colleague, Prof Paul Freemont. It is known that PCR methodology is very sensitive in antigen detection in relation to COVID-19. The SynbiCITE methodology is based on PCR using a 96 well approach and a Felix robot. The robot is programmed with a systematic workflow that can be optimised for different conditions. The method is being tested at two of Imperial’s hospitals (St Mary’s and Charing Cross). The results of initial trials indicate that the method is very reliable, with low error rates. A single robot can carry out around a 1000 separate tests per day - and can run continuously. Additionally, multiple robots can be run in parallel using the same workflow - and the method is reagent manufacturer agnostic. In my view, another major advantage of the method is that the testing and analysis can be done directly within the hospital - without the need to transport samples to major centres, which may be a significant distance away.

I will return to the other items on my list: additional testing methods for antigens and antibodies, effective diagnosis of the various stages of the disease and apps to monitor the population etc in my next blog.

Finally, a word about SynbiTECH 2020. The conference was due to be held at the QEII Conference Centre in Central London on the 6th and 7th July. Due to the coronavirus lockdown, it has had to be postponed. I’m pleased to report that the conference will now take place on the 26th and 27th of October at the QEII Centre. We also plan to run a half-day webinar (virtual conference) on the 6th of July, as a precursor to the main conference in October.