Prof. Phil Williams: I’m a third-generation pharmacist educated at the University of Nottingham. I first came to the University over 40 years ago and graduated with a Bachelor of Pharmacy (BPharm) degree in 1988. After completing my pre-registration training in community pharmacy, I returned in 1989 to undertake a PhD in Computational Studies in Scanning Probe Microscopy.

In 1996, I was appointed as a lecturer and my research has since focused on single-molecule biophysics—particularly the development and application of dynamic force spectroscopy. Alongside my research, I teach on both the Pharmacy and Pharmaceutical Sciences degree programmes, specialising in spectroscopy and drug design.

I currently serve as Associate Pro-Vice-Chancellor for Research and Knowledge Exchange within the Faculty of Science, which encompasses the Schools of Biosciences, Chemistry, Computer Science, Mathematical Sciences, Pharmacy, Physics & Astronomy and Psychology.

Prof. Phil Williams: Astropharmacy and Astromedicine involve the study of health risks associated with spaceflight and the development of pharmaceutical countermeasures and therapies to prevent, treat and manage disease in the extreme environment of space.

Prof. Phil Williams: There are a multitude of issues that impact the effective delivery of therapeutics in the spaceflight environment, requiring new manufacturing, formulation and integrated approaches. Spaceflight creates a new environment, with the two most obvious differences being the change in the effect of gravity on the body, and the increase in exposure to radiation.

In a microgravity environment, an astronaut is in free-fall and accelerating at the same rate as the local acceleration due to gravity. The immediate effect of this is on the blood, where the loss of hydrostatic pressure means it ‘pools’ in the head and thorax. Such fluid shifts create immediate changes to the blood supply to the stomach and hence changes to how food and pharmaceuticals are absorbed. For example, after one day of flight, the rate of absorption of paracetamol from a tablet is doubled.  The astronaut’s body, evolved in a 1 g environment, responds to this redistribution and reduces the blood volume, causing a halving of the peak plasma concentration after ingestion of a paracetamol tablet on day two. By day three, a balance is re-established and the pharmacokinetics (PK) is returned to Earth-like conditions. Further challenges are that this time-dependent change of PK is both subject and drug-dependent; the time variation of the PK of scopolamine, for example, is different.

This example of the case of a simple paracetamol tablet also highlights issues around the drug delivery itself. Medicines in spaceflight are exposed to increased levels of radiation and non-ideal storage conditions. Since the degradation may be dominated by ionizing radiation, rather than thermal events, the degradants of the components, including the API, may be different, and toxic. The formulation, the shelf-life, storage, and regulation, may need to be different for pharmaceuticals used in flight.

There are many obvious challenges with drug delivery in a microgravity environment – filling of a syringe; using drops – and many less obvious difficulties – how the changing microbiome affects absorption; altered interstitial pH due to elevated CO2 levels, for example. This is compounded by the change in pharmacodynamics (PD) – the up- and down- regulation of signalling pathways, possibly due to in part the known changes in membrane fluidity that may impact receptor recruitment in cells.

A significant barrier to long duration off-planet habitation and Mars-class crewed missions is what I have termed the Space-Pharmacy Wall: As mission length increases, both the number of different types of medication and the amount of each required increase. Mass is an enemy of spaceflight. The combination of the increased need of medication coupled with their decreased stability creates a limit to mission duration, if reliant on medications manufactured on Earth and carried on board. Ways to manufacture medication on-site and on-demand, preferably by reusing, recycling, and repurposing local material, is needed; a central theme of Astropharmacy.

Prof. Phil Williams: The on-site, on-demand manufacturing of medicines, critical to long-duration spaceflight, will permit medicines to the tailored to the individual astronaut at the specific point in time when they take them since PK/PD are both time and subject dependent. For drugs where the therapeutic index (the window in blood concentration between being effective and being toxic) is large, there is a degree of tolerance to changes in PK, such as in the case of paracetamol given above. However, where this window is narrow, then such changes PK cannot be tolerated, and a drug dosage safe on Earth may be fatal in spaceflight. Tailoring the medication to the individual at their particular state in time will not only optimize drug dosing and minimize waste, but is essential.

Prof. Phil Williams: The expansion of crewed space travel and the potential for space tourism is accompanied by the move away from a participating demographic of supremely fit individuals. The wider pool of space travellers may have pre-existing medical conditions, successfully managed by medication. Understanding pharmacogenics, pharmacokinetics and pharmacodynamics, something that pharmacists are specialists in, will be essential to realize such activities. Space-pharmacopeias and space-formularies are needed and with these comes to need for medicines management, regulation, safety and training.

Prof. Phil Williams: Certainly! Finding solutions to critical problems on Earth, but looking at them from a completely different perspective as in space, is the main reason for my research in Astropharmacy. If we can treat people on Mars, we can treat people anywhere!

Being able to manufacture medicines at the time and place of need, tailored to the individual, and from recycled, repurposed, and reused material, will have enormous positive impact on Earth, and not only in extreme environments. Finding ways to manage the environment, maintain health, and sustain life on Mars will provide transformative solutions for application on Earth.

Prof. Phil Williams: I think Astropharmacy is an exciting addition to current courses, but not as a standalone programme. At Nottingham, it is offered as an optional module within the School of Pharmacy, with students of Pharmacy (MPharm), Pharmaceutical Sciences, Pharmacology, International Pharmacy, and Biotechnology, for example, enrolling in recent years. We are looking to offer continuing professional development (CPD) courses, possibly expanded to include aviation and extreme medicine to pharmacists.

Prof. Phil Williams: The initiative came from a congruence of my various and eclectic, research interests. I am a pharmacist. My research in single molecule biophysics included studying protein folding and protein mechanics and used part of a muscle protein as a model. I started to work with a colleague who was studying sarcopenia and muscle atrophy and researching using nematodes in spaceflight.  Alongside this, as part of a PhD project, we started to look at differences in the mechanical properties of proteins and then if we could shed some light on how proteins had evolved their different mechanical properties. This led to a collaboration with an astrobiologist at NASA Ames, where the PhD student spent time in their labs doing long-timescale molecular dynamics simulations. I went to NASA Ames to give a talk on the work and their met Lynn Rothschild. We chatted for a while about our various research interests and then asked ourselves the question – How will we treat the first human explorers on Mars? With funding from the Engineering and Physical Sciences Research Council and the University of Nottingham, I established a PhD programme in Astropharmacy in 2018 with the first cohort of six ‘pharmanauts’ starting their PhD studies in 2019. We have research funding from the UK, Europe and US and collaborators across the globe.

Prof. Phil Williams: Current PhD research projects include the development of synthetic biology tools for the on-site production of biologics (peptide and protein-based therapeutics) using cell-based and cell-free platforms; ways to store these tools for extended times in the harsh environment of spaceflight at room temperature; design and testing of novel formulations for use in microgravity; expeditionary pharmacy and the potential of RNA-based therapeutics for extreme environments; additive manufacture of delivery systems; metabolomics and how this changes in spaceflight; design and development of CubeSat hardware for Astropharmacy experiments.

Prof. Phil Williams: Our undergraduate training in Astropharmacy is currently offered as an optional module to be taken within a degree programme, such as our 4-year Pharmaceutical Sciences MSci. With the broad field of Astropharmacy, there are opportunities to undertake PhD research training in many areas, and sometimes specific scholarship opportunities are available for projects. The current PhD students in the area at Nottingham are a mix of UK Research Council, University of Nottingham, Government Scholarship, and self-funded.

Prof. Phil Williams: Yes, we welcome all students and have a vibrant mix of people with different backgrounds from across the globe. You can go through the official University portal for further details.

Prof. Phil Williams: Embrace the excitement. Space focussed research offers a new paradigm for scientific exploration by recapitulation of a problem to give a new perspective from which solutions may be found. You will make a difference that can benefit everyone.