ASK DR SLEEP

Oxford’s Professor of Circadian Neuroscience is also known as ‘Dr Sleep’ because as anyone who has experienced jet lag knows, getting the right sleep at the right time is critical to feeling healthy and alive and ‘normal’.

Professor Foster, who heads the Nuffield Laboratory of Ophthalmology and is Director of the Sir Jules Thorn Sleep and Circadian Neuroscience Institute (SCNi), and a Fellow of Brasenose College, is a leading world authority on the subject.

At a packed auditorium at Meeting Minds, Professor Foster was introduced to the alumni audience by Oxford’s Chancellor, William Hague, Lord Hague of Richmond, who joked that his memory of being a multi-timezone British Foreign Secretary was that red wine more often than not seemed to be the best (and worst) way to try and get to sleep.

Sleep health is an enormous, frequently overlooked problem in society, explained Professor Foster, citing the RAND Corporation that estimates that £40 billion a year is lost in cost to the UK economy alone from poor or lost sleep, in the form of 200,000 lost working days to sickness. If we could better understand the impacts, we could better mitigate them.

Professor Foster is famous for unpacking the secrets of our circadian rhythms – ‘circadian’ describing processes that happen on roughly a 24-hour cycle, originating from the Latin words ‘circa’ (around) and ‘diem’ (day).

He recounted that in the early 2000s, his research led him to begin to argue that the body must have a different mechanism for processing light than just the eyes, partly because mice still do well without cones and rods in their eyes. It was also beginning to be understood that some blind people also seem to manage well.

The long-standing broad consensus – with which he agreed in the main – was that bodily rhythms were organised by light recognition. Just ask the citizens of Tromso, Norway, where in the 24/7 darkness of a Nordic winter they will treat themselves to a ‘photon shower’ in the mornings with light therapy, sitting in front of bright lights. Or consider why flight attendants make you pull down the window blinds to simulate night time even if it’s blinding white outside.

But establishing the mechanism behind it all was a controversial, emerging area of research. A quarter century later and with a best-selling book to explain it all, Life Time, Professor Foster argued that we are at a point where it is correct to talk about a ‘circadian system’ rather than an older notion of a ‘biological clock’.

At the centre of the discovery are photosensitive Retinal Ganglion Cells (pRGCs), described by Professor Foster as a ‘photo sensitive net across the eye’, and ‘truly beautiful’. Not a ‘master clock’, this light processing mechanism communicates itself to ‘periperal clocks’ all over the body – a circadian system in the full sense.

The implications of this discovery are still being assessed, but are simply enormous.

One insight that has emerged from additional research concerns the right time of day to take a medicine. The research suggests extraordinary differences in survival rates for the time of day a particular drug is taken, by patients suffering everything from ovarian cancer to children with leukaemia. It can be as much as double.

One of the commonest health problems is high blood pressure, and the German medical profession talks about the ‘Todeszone’ (death zone), with stroke risk high between 6am and noon. It has led to a newly emergent thesis that blood pressure medication might be best taken at bedtime rather than first thing in the morning, Professor Foster said. He further offered that if you get a vaccine for the flu or COVID, it is better to receive it in the morning.

More broadly he discussed the 20% cognitive impairment associated with driving at 5am, before we are fully awake. He noted that residual alcohol presence from the night before has occupied much discussion, but cognitive impairment from circadian disruption, often confused with plain old fatigue, is far less familiar but potentially deadly.

Night shift workers suffer from all the problems associated with deliberately contradicting the circadian rhythm, and for example suffer from much higher than average rates of certain illnesses – including cancer – and divorce.

In fact the listed maladies might alarm anyone who works strange hours, such as in hospitals or factories. There is an acute impact on emotional responses (mood fluctuation, anxiety, frustration and so forth), cognitive performance (concentration, decision-making, motor performance) and more broadly on physiology and health (cardiovascular disease, reduced immunity, type 2 diabetes, depression, psychosis and dementia).

In the rest of his talk, Professor Foster went further to explore other permutations of the circadian rhythm, such as the fact that it may weaken a bit as we age, explaining perhaps why the elderly often report sleeping more lightly. He also discussed that there appear to be profound differences between the genders, based on menopause, an area where there is still insufficient research; and that some animals appear to possess further circadas, associated perhaps with hibernation, where annual or multi-annual cycles sit on top of the daily rhythm. The menopause is one such secondary cycle that sits atop the daily one.

Perhaps most excitingly, for people who have lost their eyes completely, there are emerging medications that appear to halt what is referred to as ‘circadian drift’, experienced as a feeling of being a bit jet-lagged constantly. Combined with light therapy, there is hope on the horizon for people with this condition – and in time there may be the same sort of relief for the jet-lagged too.

In this regard Professor Foster spoke with genuine excitement about an emerging new drug, CT 1500, already proven to halt circadian drift in blind patients and which could be useful in addressing eye damage, dementia and other forms of mental illness and neurodegenerative disease – and quite hopefully might be one day obtainable in a form that can be easily taken to reset our clocks after a holiday in a different timezone.

The drug operates by modulating adenosine signalling in the brain's suprachiasmatic nucleus, the body's master clock, and it is being developed by Circadian Therapeutics – a spin-out company from Oxford founded to develop the very therapies discovered by Professor Foster’s research.