Tag Archives: drugs

Seeing things with nanoparticles

Photograph showing optical microscope and ancilliary equipment set up on an optical benchLast week brought excitement and disappointment in approximately equal measures for my research on tracking nanoparticles [see ‘Slow moving nanoparticles‘ on December 13th, 2017 and ‘Going against the flow‘ on February 3rd, 2021]. The disappointment was that our grant proposal on ‘Optical tracking of virus-cell interaction’ was not ranked highly enough to receive funding from Engineering and Physical Sciences Research Council. Rejection is an occupational hazard for academics seeking to win grants and you learn to accept it, learn from the constructive criticism and look for ways of reworking the ideas into a new proposal. If you don’t compete then you can’t win. The excitement was that we have moved our apparatus for tracking nanoparticles into a new laboratory, which has been set up for it, so that we can start work on a pilot study looking at the ‘Interaction of bacteria and viruses with cellular and hard surfaces’.  We are also advertising for a PhD student to start in September 2021 to work on ‘Developing pre-clinical models to optimise nanoparticle based drug delivery for the treatment of diabetic retinopathy‘.  This is an exciting development because it represents our first step from fundamental research on tracking nanoparticles in biological media towards clinical applications of the technology. Diabetic retinopathy is an age-related condition that threatens your sight and currently is managed by delivery of drugs to the inside of the eye which requires frequent visits to a clinic for injections into the vitreous fluid of the eye.  There is potential to use nanoparticles to deliver drugs more efficiently and to support these developments we plan that the PhD student will use our real-time, non-invasive, label-free tracking technology to quantify nanoparticle motion through the vitreous fluid and the interaction of nanoparticles with the cells of the retina.


Reduction in usefulness of reductionism

decorative paintingA couple of months ago I wrote about a set of credibility factors for computational models [see ‘Credible predictions for regulatory decision-making‘ on December 9th, 2020] that we designed to inform interactions between researchers, model builders and decision-makers that will establish trust in the predictions from computational models [1].  This is important because computational modelling is becoming ubiquitous in the development of everything from automobiles and power stations to drugs and vaccines which inevitably leads to its use in supporting regulatory applications.  However, there is another motivation underpinning our work which is that the systems being modelled are becoming increasingly complex with the likelihood that they will exhibit emergent behaviour [see ‘Emergent properties‘ on September 16th, 2015] and this makes it increasingly unlikely that a reductionist approach to establishing model credibility will be successful [2].  The reductionist approach to science, which was pioneered by Descartes and Newton, has served science well for hundreds of years and is based on the concept that everything about a complex system can be understood by reducing it to the smallest constituent part.  It is the method of analysis that underpins almost everything you learn as an undergraduate engineer or physicist. However, reductionism loses its power when a system is more than the sum of its parts, i.e., when it exhibits emergent behaviour.  Our approach to establishing model credibility is more holistic than traditional methods.  This seems appropriate when modelling complex systems for which a complete knowledge of the relationships and patterns of behaviour may not be attainable, e.g., when unexpected or unexplainable emergent behaviour occurs [3].  The hegemony of reductionism in science made us nervous about writing about its short-comings four years ago when we first published our ideas about model credibility [2].  So, I was pleased to see a paper published last year [4] that identified five fundamental properties of biology that weaken the power of reductionism, namely (1) biological variation is widespread and persistent, (2) biological systems are relentlessly nonlinear, (3) biological systems contain redundancy, (4) biology consists of multiple systems interacting across different time and spatial scales, and (5) biological properties are emergent.  Many engineered systems possess all five of these fundamental properties – you just to need to look at them from the appropriate perspective, for example, through a microscope to see the variation in microstructure of a mass-produced part.  Hence, in the future, there will need to be an increasing emphasis on holistic approaches and systems thinking in both the education and practices of engineers as well as biologists.

For more on emergence in computational modelling see Manuel Delanda Philosophy and Simulation: The Emergence of Synthetic Reason, Continuum, London, 2011. And, for more systems thinking see Fritjof Capra and Luigi Luisi, The Systems View of Life: A Unifying Vision, Cambridge University Press, 2014.


[1] Patterson EA, Whelan MP & Worth A, The role of validation in establishing the scientific credibility of predictive toxicology approaches intended for regulatory application, Computational Toxicology, 17: 100144, 2021.

[2] Patterson EA &Whelan MP, A framework to establish credibility of computational models in biology. Progress in biophysics and molecular biology, 129: 13-19, 2017.

[3] Patterson EA & Whelan MP, On the validation of variable fidelity multi-physics simulations, J. Sound & Vibration, 448:247-258, 2019.

[4] Pruett WA, Clemmer JS & Hester RL, Physiological Modeling and Simulation—Validation, Credibility, and Application. Annual Review of Biomedical Engineering, 22:185-206, 2020.