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How can you resist a jelly bean with a propeller?

Back in the mists of time, I was a research chemist for a large pharma company. I worked on anti infectives (mostly antibacterials) for many years. I was one of many trying to extend the useful life of beta-lactam antibacterials (including the penicillins) whose usefulness was being compromised by the three pronged attack of over-prescription, bacterial resistance and patient non-compliance. All three of these intertwined in the developing story of resistance to medicines that came to the fore with the public awareness of MRSA and has grown ever since. It became a government priority described in its AMR programme which was kick started by Prof Dame Sally Davies in 2011, leading to the O’Neill report and NIHR themed calls targeting AMR between then and now.

At the time my employer was making its contribution to the ‘resisting the bacterial resistance’ by developing Augmentin, a penicillin co-formulated with an inhibitor of the pesky beta-lactamase enzymes that bacteria were developing with remarkable speed. Alongside this we were trying to develop a penicillin that would retain its activity with once a day dosing as so many patients would not, or could not, keep to a three or four times a day regime.

It was an exciting time while being one of incredible naivety too. The view that bacteria were beaten began to circulate in management circles as sales of Augmentin went past the £1 billion per annum mark. Around the same time life style changes were working on a societal level creating new therapeutic priorities in mental health, circulatory disease and treatment of ulcers. It was convenient in the minds of some leaders to join these two influences and make the case for taking the focus away from bacteria. I mean, it’s not as if they are adaptable to change is it, what with only reproducing a new generation every 20 minutes or so?! A cynic might have added the comment that the low cost per dose for antibacterials tends to make them unattractive to pharma companies given their development costs. This is certainly something that the government are aware of. They are trying to find an ethical way of supporting antibacterial research in the private sector that is not anticompetitive – good luck there then!

Around the same time I was one of an army of people trying to improve the public perception and understanding of science. After all you had to have some sort of attenuation for the stupidity of some ‘scientific’ views (see above) and/ or rather inaccessible communication skills that tended to go with the territory at the time. I was also part of a small group from across the company encouraged to ‘think outside the box’ or do ‘blue sky thinking’ in all matters pharmaceutical. It was atypical at the time to be encouraged to think creatively in the workplace, without boundaries. Once we were used to it we had a great time foreseeing (and taking action on) what would become a number of game changes in medicinal chemistry.

My own favourite day dream was to be able to create a synthetic bacteria who would fight fire with fire, function like a Trojan horse or any other metaphor of your choosing! You can imagine my delight when I found out years later that there is no need for a synthetic bacteria to do this job, there is a natural one.

I was reminded of this last year when listening to the Life Scientific on BBC R4 when Liz Sockett was being interviewed. She described her work on Bdellovibrio (silent B, thank goodness) in a totally accessible and fascinating way by bringing it to life using brilliant metaphors. She is the antithesis of the scientific geek communicators of the 1980s. She realises the responsibility for ensuring a message lands properly resides with the communicator, not their audience. She also drew me in with a comment central to her approach to AMR which reminded me of my earlier blue sky thinking: if you want to know how to kill a bacteria, ask a bacteria!

She described Bdellivibrio as being ‘a jelly bean with a propeller on one end and a grappling hook on the other’. The propeller means it can swim 100X its body length in a second (eat your heart out Ian Thorpe!), a faster mover than any other bacteria. It was this swimming speed that led to her first research question: does it allow the Bdellovibrio to batter its way into its host cell (which, by the way, is specifically gram negative bacteria). The answer was no.

Instead, with beautifully accessible language she described how Bdellovibrio used something like a fireman’s ladder to extend towards the surface of its host at which point it activates a glue to stick it to the surface. It then draws the ladder back in, and once sitting next to the host’s cell wall, the chemistry really begins.

It interferes with the cross links of the garden trellis-like structure of the gram negative bacteria’s cell wall (as it happens this is the target of pencillins too) and creates a pore like a polo mint that it opens in front of it and closes behind. On reaching the cell membrane it manages to inject a cocktail of enzymes through the cell membrane without any harm to itself – a remarkable feat in its own right as the cocktail is as poisonous to the jelly bean as it is to its host. The enzymes break down the molecular structure of the host killing it in the process and providing food for the Bdellovibrio that eventually busts out of the host cell. Liz described her workers observing a 15 second long molecular scream from the host cell as it tries, without success, to fight off the jelly bean’s death serum.

So by means of reference to jelly beans, a propeller, fireman’s ladder, glue, polo mints and a molecular scream, Liz Sockett brought a complex subject to life in an accessible way. Her interview was a reminder that great science also needs to be communicated well and she managed both in spades. Her work, along with that of many others is slowly progressing the use of Bdellovibrio in a therapeutic setting from possibility towards probability and eventually reality.

I was left with two reflections. First that it was great to hear about those who think those blue sky thoughts and work to make them a reality. Second was my interest in language and the use of metaphor that has been re-energised in coaching conversations I have with clients. It is amazing how, by talking about what our thoughts and behaviours are like, it is possible to gain a clearer view of ourselves and the way we actually are.

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