Here comes the sun

There is a long stretch of British winter when we get up in the dark, go to the work in the dark and return home in the dark. You can go for whole days without a single photon from the sun landing on your body. But some time in late February chinks begin to appear in night’s mantle. And we are now reaching that magical tipping point, when you can feel the longer days accelerating towards you, curtains become more than just snooper prevention, birdsong returns to the soundscape. The only downside is that sunrises are no longer part of the day’s palette (except for the really keen).

All of which might seem unimportant in these dark days, but daylight is a vital ingredient in our health and well-being. We can sense light even when we cannot see it. Blind people can tell when lights were off or on in. And studies in the 1920s showed that blind mice still responded to the light (that’s how they detected the carving knife presumably). We sense light through a third type of cell in our eye (in addition to rods and cones) these cells are called pRGC photoreceptors.

Daylight also steers our biological clock (the circadian rhythm in science speak). Unconstrained by the light, our daily rhythm is determined by a family of genes and varies between 23.5 and 24.5 hours (explaining larks and owls). However, this natural clock is over-ridden by daylight which acts as a zeitgeber (from the German for time-giver).

This is important because living our lives out of time has a significant negative effect on healthspan. People who undertake shift work have a considerably higher risk of a range of diseases, including cancer and dementia. This is most probably because our body clock sets the production and release of 2 key hormones: cortisol, which rouses us in the morning and melatonin, which calms us down in the evening (the body’s equivalent of caffeine and camomile). Excess cortisol leads to a misfiring of the immune response, enhancing inflammation which has a range of bad effects.

Being outside in the daylight has a slew of other benefits, not least the production of vitamin D. Though care is required as we move into the spring months, when UV intensity is at its highest (preceding the hotter months). So do slap on the sun cream, we can still produce vitamin D, even through the SPF.

The final benefit of the lengthening of days is that it encourages us outside to commune with nature. And whilst winter walks have a value, there is no greater balm for the soul than the fresh green of newly emerging leaves. Trees have a curative, restorative value - as shown in a study in the 1980’s when patients who could see trees self-medicated less and left hospital earlier.

The return of the sun also heralds warmer days, with opportunities to socialise in parks and gardens. So throw those blinds open wide and let the daylight in.

The not quite as tricky second book.

 My new book is out - buy it please!

It began as all the best things do, with a cup of tea. I met up with the wonderful Caroline (Hardman, my agent) at Somerset House. We discussed my first book Infectious and drifted onto the subject of whether I would consider penning another. I’d not really intended to, it wasn’t necessarily a small undertaking – consuming nearly every weekend for 9 months (admittedly this was during the worst of lockdown, when frankly there was nothing to do anyway!).

Infectious, unsurprisingly, covered infectious disease and the many ways in which you can die. I’d started it with the cheery statement: ‘Nature wants you dead.’ But the main point of Infectious was that thanks to science, far fewer people died following infection – even at the peak of the pandemic.

‘So what do people die of then?’ was the follow up question that launched Live Forever; which then morphed into – what might I die of? This had begun to plague me a bit, the signs of ageing beginning to creep up on me – holding my phone further from my face, the odd grey hair, the daily aches and pains. So I set out to explore my proximal causes of mortality and importantly if there was anything I could do about it.

In this I had some assistance from the many scientific experts at Imperial with whom I discussed the details of disease. But because there was more about me in the book, it took a different direction. The first difference was that I undertook a number of self-experiments to test all those things that wellness gurus suggest might help delay death (extreme diets, cold water swimming, feeding kimchi to my microbiome). The second was in the structure of the book. It became a narrative journey. In this aspect I was very fortunate to meet the screenwriter (and actor) Ben Willbond. We were at a history festival together and I screwed up the courage to ask him about how he writes episodes. He directed me towards Will Storr’s excellent book The science of storytelling. He also nudged the book onwards when maybe the science got too heavy and the story too light. Critically he introduced me to the idea of the 4^th act, but you’ll have to read Live Forever (out today) to see if I quite landed it. He wasn’t the only person from the creative side who helped with suggestions of process – the conversations led to an article we published in Nature which I am reasonably sure is the only one in that esteemed journal to ever feature Schrodinger’s cat’s butthole.

(Courtesy of Richard Tillotson – buy his cards here)

Writing a second book, even though it was on a different topic to the last book and one notch removed from my normal research, was definitely easier. The first I really had no idea what lay ahead of me. This time I had some routines and knew the absolute need to just keep writing. 9 months seems quite long at the beginning, but it slips away and that need to get 5,000 words down every weekend doesn’t go away, you just end up having to play catch up the following week.

One of the things I really loved this time was discovering new facts. Which I then shared with my family and work colleagues. Often several times. ‘Did you know that…’ induced a Pavlovian reaction in them. I stand by some of the facts being both funny and interesting. The people who had to endure them as they were honed may disagree. My absolute favourite page has 10 different sausage jokes on; each of them high quality eye-rollers. Though when I asked my editor 'Are there too many dick jokes'; I was pretty sure that was not a conversation George Elliott ever had.

One of the highlights of the writing time was that I took on a writing retreat in Cornwall. This may sound really pretentious, and it was. But it was also extraordinarily productive. I wrote 15,000 words and then proceeded to cut 30,000 words from the final draft. I was blessed with a perfect winter’s week of crisp skies and beautiful sunrises. I got to run every day. The only person I met was the publican, the owner of the local shop and the same woman walking her dog who I bumped into twice.

A writing retreat

I would strongly recommend taking time out to do something you love, though it does rely on one key factor – familial tolerance. This book would not have happened without the ongoing support of my family. Particularly my wife who had to take up a lot of the slack whilst I was ‘creating dah-ling’. Before starting, I’d not really spoken to the rest of my family about the consequences of sequestering myself away for another year. I’d not really planned on writing another book. I have no idea if I have a third in me. But am saying thanks now – in advance.

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Taking the Plunge

 On the benefits (or not) of cold water swimming

I dip my toe into this topic with some considerable caution and not just because it is bloody cold. Cold water swimming has an enthusiastic, dare I say cult following. This includes at least 2 of my colleagues, a handful of friends, my cousin and my sister. All of whom took umbrage when I dared to question its unique benefits.

Much has been made of cold water swimming as a panacea, often in the context of ageing and wellness, particularly by those who sell retreats which involve cold water swimming. And I’m not completely against the idea. It can be the best feeling, I’ve some in mountain lakes in Switzerland, Wales and the Lake District. Quite a few of those dips have been naked because I forgot to bring my trunks. On one memorably terrible time, I was about to take the plunge and for some reason decided to take my wedding ring off for safe keeping, immediately losing it on the shale of Brighton beach. In some miracle of modern technology, a friend used his phone torch and found it.

As part of the research for my book Live Forever? A Curious Scientist’s Guide to Ageing, Wellness and Death I undertook a number of self experiments. One of which was cold water swimming. I’ll confess now, I didn’t go hardcore – I waited till late March (average water temperature 10°C) as opposed to the current water temperature in the UK (3°C).

I recorded the outcomes in an entirely subjective way.

Day 1. Weather rainy and windy; sea temperature ten degrees Celsius. Alone (my daughter refused to join me because of the rain). Length of time in sea – five minutes. It was only this long because I shared the beach with someone else who had clearly just been swimming and I felt ashamed by my weakness.

Day 2. Weather rainier; sea temperature still cold. With daughter for five minutes, but she got out quickly because she only had one sea shoe – the matching one having been lost six months previously. Length of time in sea – ten minutes. I lasted longer because I remembered my wetsuit gloves this time.

Day 3. Weather windier; sea temperature unknown. With family. Length of time in sea – zero minutes. We had changed beaches to the rougher north Cornish coast to discover waves crashing on the sea wall with enough force to break bones. Whilst internal bleeding probably would lower blood pressure, we decided that discretion was the better part of valour.

Days 4–6. Some sun, not warm. With extended family. Length of time in sea – thirty minutes.

Because I am a proper scientist, I repeated the whole experience a year later – no reproducibility crisis in my research! I confirmed the original findings, the English Channel in late March is bitterly cold, but spending time in it with my family is fun. Sea-swimming did seem to resolve a calf injury I had given myself, so score one to the curative properties of cold salty water.

From my studies, it looks like I made some amazing breakthrough in resilience, but being honest, most of the increase in swim length came about because the weather improved and I remembered all the right bits of kit. Having (finally) warmed up, I looked into the delicate balance between the pros and cons of cold water swimming. Cold water swimming is not without risk. Most advice emphasises that cold water can lead to shock, arrhythmia and hypothermia; none of which sounds that healthy. One scientific paper stated that whilst cold water has some health benefits for the already healthy, ‘there is a risk of death . . . either due to the initial cold shock or progressive decrease in swimming efficiency’.

One of the things often attributed to cold water swimming is immune boosting, with anecdotal evidence about reducing the number of colds swimmers get. We discussed this at length on a recent episode of Inside Health on BBC Radio 4 so after reading this, listen and draw your own conclusions!

I do sometimes wonder if in this secular age, there is a more sacral component to the cult of cold. Doing something slightly flagellistic with other like minded souls. In the end the benefits come back to the key lesson I learnt whilst researching for my book – social connectivity is good for us. So if this works for you, carry on. The combination of physical and social has a synergistic benefit on our lives. (But do take care – especially on a windy day like this, swimming can be dangerous). But if you prefer not turning blue on a beach, try something else. In the end, the answer of how to live longer and better is do more of what you like with people you love.

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Ageing and Love

Inexplicably buried in the calendar is a date with an expectation for romance, gifting and fine dining. It is easy to be overwhelmed by commercialisation but at the heart of it is something important.

One of the good things about ageing is that there is a decreasing number of times we have to endure Hallmark moments – fewer father’s days, half as many Halloweens and vanishing numbers of Valentines. This may sound grinchy but there is something quite depressing about enforced enjoyment. Coupled with the grim commercialisation of these dates; the pressure to buy rubbish that goes straight from the factory in China to the bin in Britain. Don’t get me started on dressing up; the absolute state of Christmas jumper day – no they aren’t funny, they are just naff. And as for the trauma of world book day, yes my children are no longer cute angels, but at least I no longer have to spend the night before desperately throwing clothes together and trying to persuade them that yes Harry Potter definitely wore this. As an aside, has anyone ever been convinced to read more books because they got to dress up as Spiderman? My guess is that people who enjoy reading are not necessarily people who enjoy fancy dress.

Ah, it felt good to get that off my chest. And it’s easy to be cynical. Cynicism being an attribute that matures with age like fine wine – or alternatively begins to stink like old cheese. And until the last year I genuinely couldn’t see a point to many of these occasions. In writing my book Live Forever? A Curious Scientist’s Guide to Wellness, Ageing and Death I investigated various ways we could extend our lives. Most of them didn’t work, some were not surprising (don’t drink, don’t smoke, do exercise, eat healthily), but one was surprising (and reassuring). Social connectivity is good for us. So finding ways to come together with other people is a health hack.

So instead of dreading the various set pieces throughout the year, see them as a chance to connect. And focus on the aspects that matter to you. For some people, fancy dress is a wonderful way to demonstrate their creativity and shared interests (admittedly not me, I would rather die alone than cosplay). For others preparing lavish meals, carefully sourcing each person’s favourite treat; or choosing gifts that perfectly match the person. These love languages are important, but central to the possible health benefits are time together and connectivity. Sometimes this can get lost when the focus is on buying rather than doing. But let’s claim them back, and this year’s Valentine’s day, Mothers day, Easter, Halloween etc do more of what you like with people you love.

 I am slowly migrating content onto substack.

So if you have been following me there please follow me https://substack.com/@professortregoning 

Follow me

 I am slowly migrating content onto substack.

So if you have been following me there please follow me https://substack.com/@professortregoning 

Thank you for reading everything on here over the years.

Will still try and cross post where possible

The complex relationship between viruses and our immune system

 Virus Appreciation Day, celebrated annually on 3 October, serves a dual purpose: to foster respect and understanding for viruses while raising awareness about their serious impacts on health. To mark the day, Professor John Tregoning from Imperial’s Department of Infectious Disease shares valuable insights into influenza viruses, highlighting their effects, the importance of vaccination, and ongoing research for universal vaccines against evolving strains in our latest blog.

Viruses have an enormous impact on human health, but they don’t only infect humans. Many viruses also infect animals, plants and even bacteria. Some viruses are quite promiscuous, infecting a wide range of animal species before passing on to humans through a process known as zoonotic transmission. One of the most problematic of these zoonotic infections is influenza virus.

The main natural reservoir of influenza virus is wild birds, particularly ducks and geese. The virus can then transmit from these birds into domestic poultry, like chickens, and to livestock, such as pigs, before ultimately reaching people. In the past five years, a new strain of avian influenza has emerged with an ability to infect an even wider range of mammalian species. It has been detected in cattle in the US.

Influenza, the disease caused by the virus, poses a substantial health burden. It resulted in nearly 15,000 deaths in the UK in the 2022-23 winter season. As well as death, it is a significant cause of hospitalisation and general illness – with a long tail of recovery. Additionally, influenza infection doubles the risk of heart attacks and strokes for up to a year after illness. Given these risks, getting an influenza vaccine this time of year is highly recommended. As I discovered researching my latest book Live Forever one of the simplest ways of extending your life is through vaccination. A vaccine will give you protection against the most severe forms of disease caused by the virus and protect you against subsequent illness.Vaccines train your body to recognise pathogens and fight them off. To do this, they make use of a facet of immunity called immune memory. When re-exposed to the same virus, your immune response activates faster and stronger, stopping the infection in its tracks. Several aspects of immune memory can prevent subsequent infections, but an important one are antibodies – this is a type of protein that is highly specific in what it can recognise and bind. When you are immunised with influenza vaccine, you make influenza virus specific antibodies that can stop the virus from infecting you.

However, influenza virus is a tricky customer. It changes its coat in an attempt to escape antibodies and this means that the vaccine can become outdated – necessitating boosters each year. These different types of virus are called different strains. A huge goal in influenza vaccine research is to make a vaccine that can recognise a wider range of different influenza virus strains, even as they mutate to evade the immune response. These are called universal influenza vaccines; ideally you would be able to have a single immunisation and get lifelong protection.

But there are a number of potential hurdles in the path to developing such a vaccine, these relate to the virus itself, but also how our immune system works and forms memory. One facet of the immune response that we have been investigating recently is called ‘original antigen sin’ – which is not a particularly catchy name. What it refers to is how the first exposure to a series of similar looking viruses affects subsequent responses. It’s a bit like how babies learn to recognise people – the first woman a baby recognises might be called mummy and subsequently they might refer to all women as mummy (at least for a while). In the case of original antigen sin, the immune system may focus on familiar elements of different viruses at the expense of recognising new or changing parts, leading to inefficiencies in responding to variations.

 The problem with studying this is that human’s exposure to influenza is extremely complex – we have all been infected at different times with different viruses, some of us will then mix this up with a vaccination leading to a natural history of disease that is very hard to interpret. In our most recently published work in The Journal of Infectious Disease, we used a different approach to understand the immune response to influenza infection. Through a collaboration with the pharmaceutical company Sanofi, we performed experiments on a type of mouse called the Kymouse that has been genetically engineered to make human like antibodies. This allowed us to explore how antibodies change following infections with different strains of influenza virus. Our studies suggested that infection with one strain can affect the response to a subsequent infection.

Want to Learn more?

This complex interplay of virus and human immune response is an endlessly fascinating subject, unlocking its secrets can help us identify new ways to protect humans (and chickens) from infection with a deadly virus. But don’t restrict yourself to learning about it on Virus Appreciation Day – if you have found your appetite whetted – why not try our FREE massive open online course called Foundations in Virology and Vaccinology. It does exactly what it says in the link, giving an overview of viruses and vaccines, what we know about them and what we hope to discover.

Starve a cold

 

One thing you have probably noticed when you have an infection is a profound loss of appetite? In healthy adults, this could be seen as something of a blessing, it can have much more serious consequences, particularly at the extremes of age. In the elderly, the after effects of respiratory infections can accelerate frailty and the loss of independence. In the very young, not feeding can lead to dehydration and possibly contributes to more severe disease.

In previous studies, we observed that the loss of appetite was associated with the immune response to infection. We were interested as to what might drive the loss of appetite – with a view that understanding how it occurs might lead to approaches to reverse it. In particular we wanted to understand one component of the immune response – the cells that are recruited to the lungs to fight off infections and the way that they communicate with other cells.

In our recently published study we looked at one of the signals produced by immune cells, a molecule called Interleukin 1 alpha (IL-1α for short). Cells release IL-1α to warn the rest of the body that an infection is happening and as a way of recruiting reinforcements to help in the fight. We saw that the peak of IL-1α release into the lungs just precedes the weight loss, and therefore suspected it played a role. To test our hypothesis (IL-1α causes weight loss during infection) we took two approaches. Firstly, we blocked it during the course of infection; when blocked there was no weight loss. Secondly, we added IL-1α by itself; when we did this, we observed weight loss. Put together, these observations strongly suggest that IL-1α released by immune cells reduces the appetite, and leads to weight loss.

We then looked deeper into how this might happen. And we found a really striking result – IL-1α levels increase in the brain during infection. We think this is linked to an increase in permeability between the brain and the rest of the body, which allows molecules to enter the brain which would otherwise normally stay outside. The IL-1α in the brain then triggers a cascade of hormones, in particular one called leptin, which is linked to feelings of satiety (if leptin goes up, you feel full and stop eating). Famously mice lacking the leptin gene are enormously fat because they never stop eating.

One other curiosity in our results was that when the mice stop eating, the bacteria in their guts change. These changes increase certain families of bacteria – some of which are linked to recovery from infection. This suggests the intriguing possibility that there is a protective value in not eating when you have a cold, because it increases protective bacteria – we have yet to explore this fully.

Overall, we have dissected a pathway that links the immune response to infection to a loss of appetite and discovered a key appetite regulatory role for an immune molecule IL-1α. The next step is to explore how this can be approached therapeutically.