Can We Live Forever - Edinburgh Science Festival

This is the first of two blogs written on the back of my Edinburgh Science Festival talk earlier this year. The first about ageing research generally, the second is about the drugs.

I was delighted (well one has to say that) to be invited to take part in the debate on drugs to treat ageing along with Prof Tom Kirkwood and  Lynne Cox At the Edinburgh Science Festival. Tom is, in my opinion just about as world expertly as you can even get on ageing and Lynne works directly on rapamycin so I was at first surprised to be invited along to join them. ...but then there is currently quite a lot of hysteria and nonsense published in newspapers about these drugs (rapamycin, resveratrol, metformin etc) and I suppose I am well known to be unable to help myself for ranting on about this!! So I guess that is why I was asked. That being a long winded way of saying, that whilst I would have loved to have shown up and said "its all very promising and exciting" (which it isn't), but even if I believed it, that was not my remit!

So what is the status of ageing research? In the words of the debate... "Can We Live Forever"? Now lets translate "forever" to "for a thousand years or so". Can we? Well that we can is the claims of some very famous writers on the topic.

In 2004 Aubrey de Grey famously told the BBC that the first person to live to 1000 has already reached 60. Now Aubrey de Grey is a fine writer and (read his bio on Wikipedia) has become quite famous for this, but lets face it, with a name like Aubrey de Grey and a hansom beard like that you've kind of got to be haven't you!

"The first person to live for 1000 years may already be 60 years old".  Or they might not be of course.

I frankly don't believe this for a moment. Sadly, I expect many people who were 60 in 2004 have probably died already and those that haven't now have a life expectancy, on average, of about 15 years. Sorry guys. But the claim got attention, wealthy people who are desperate to live for ever, probably plough money into the research Institute and hopefully something medically useful will come out of it. Albeit, not immortality. Some big noisy writers on the topic of living forever include Ray Kurzweil, I say "writers" deliberately. I don't see a lot of evidence that some are actually real scientists (??). Their thesis is (my interpretation) if you believe every newspaper headline about life prolonging strategies (drinking loads of red wine, avoiding salt, eating buckets of vitamins and antioxidants, avoiding calories as far as possible) it will prolong your life for the decades necessary for someone to find a total "cure" for ageing. I think that is deluded, desperate and dangerous.

Deluded? It's just scientifically without foundation. Just because a vitamin deficiency causes illness, it doesn't mean a massive excess is beneficial. Chemical balance between oxidation and reduction is a normal part of animal (including human) biochemistry and you muck it up at your peril. 

Desperate? My impression is that they are irrationally keen to live on forever. Why? To me it's like, well money is nice, but do you really need all the money in the world to be happy? The medical issue in the world is people and our pets dying early. ...and disease, chronic pain and disability in the elderly. ...but if I accept that they honestly desire to live forever (as opposed to exploiting desperate and ill people by persuading them to by the books in full knowledge its nonsense)... this methodology is rubbish anyway!! 

Dangerous? Their bottom line is that we should ignore official medical advice and do loads of extreme home remedy interventions which will probably do more harm than good.

So do I believe we can live for 1000 years?  Well I read a lot of science fiction and really this is where we are now. There is no foreseeable "cure" for ageing as such because it is not a disease.  Ageing is probably not an evolved feature involving genes which age you that can be deleted, more it is a case that EVERY gene has been geared to the survival of the young for long enough to breed. Beyond that, we are evolutionarily ignored.  Changing ALL the genes to allow infinite life is sci-fi and the one-drug-to-treat-them-all idea is ridiculous. To change breeding habits of humans is out of the question, ...but in animal models where we can work for generations of creatures I think we could double or triple life expectancy. I'm thinking pedigree dogs.  Take the poor Bernese with a life expectancy of 6 years.  If you only bred from long lived animal lines (looking back at the Dam and Sir's ancestry) I think you would pretty soon (dozens of years) be able to get these creatures to live MUCH longer ...and of course bringing some longer-lived breed blood lines into the pure breed would potentially change the breed characteristics little, but speed the process up a lot. So why does nobody do this? Go Figure.

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The Physiological Society Benevolent (Financial Hardship) Fund

This not a blog... just a plug for the Physiological Society's hardship fund called the Benevolent Fund (or BenFund for short).  If you have an extreme financial crisis and work or study in a Physiology type of discipline, it might be worth checking it out.  I am now the Chair.
The link is here

Cheryl's Birthday

OK, so here is my solution to the problem:

So the question states that Albert (A) knows the month and Bernard (B) knows the day. Since Initially, B does not know when the birthday (BD) is that immediately rules out the two dates which occur only once in the possibilities (19th and 18th).  The BD therefore cannot be the 19th May or the 18th June.  

Now, how does Albert know that Bernard does not know when the birthday is?  Assuming Cheryl only has one BD per year (unlike HRH Lizzie Windsor, Queen of UK who has two!) it can only be because he knows that the month he was told does not have a unique date in it.  Since May and June both have a unique date in them, these two entire months are ruled out.

Now on hearing that Albert has now ruled out May and June, Bernard can only possibly know which day in July or August it is because the day could not have been known before excluding May and June, but is revealed with this new info.  That could have been either 16th July or August 15th OR August 17th.  He would now know, but we still don't.  Until Albert reveals that he does now know.  He can only know because the month he knows to contain the birthday only had one date which would be revealed to him in this situation. Ergo 16th July...

Are you with me!!???

Also, for the record, everyone is posting this as "are you smarter than a small Singaporean child".... eerm... well we have heard this question was in their paper.  We haven't heard how many got it correct!  I guess we could expect 10% to have done so if they guessed ;-) 

Teaching Old Drugs New Tricks

My blog on drugs to treat ageing dogs: Copied from the University Liverpool Website: 

“Rapamycin is an old immunosuppressant drug that is now being re-investigated for its so-called ‘anti-ageing’ properties, not only for us but also, as reported recently in all the newspapers, for our canine companions (see Nature report on University of Washington in Seattle study).

So I ask myself; will a pill to increase lifespan really help us and will it help our dogs?

On the face of it, stopping the ravages of time seems a good idea. There are, as a consequence, lots of putative anti-ageing compounds under investigation at the moment. “Anti-oxidants”, curcumin (the chief component of the spice turmeric), green tea extracts, and my personal favourite resveratrol (found in red wine) are all under investigation, but my excitement is in our increasing understanding of how and why we grow old, rather than any marginal longevity gain with some “nutraceutical” or another.

Mechanisms of deterioration

The objective should surely be to increase our understanding of the mechanisms of deterioration rather than to just pump ourselves (and now our pets) with herbal remedies or other chemicals and play “Last Man Standing”.

A question that many ask is; is it even a good idea for us to interfere with such a fundamentally natural process as human ageing?  My answer is ‘yes’, obviously, because whilst there are occasional scare stories suggesting people will live for 1000 years and the planet will be completely coated by humanity several layers thick… most people researching ageing are actually researching disordersassociated with ageing such as frailty, osteoarthritis, Alzheimer’s Disease, for example.

The aim is to deliver a better quality of life rather than some miserable immortality.

Trialling these drugs in dogs first is a sensible idea though. They are reasonably safe, although nothing is entirely without risk and mechanisms of ageing are similar between animal species, but are essentially sped up in mice and canines.The study should therefore return data far quicker than it would come back from a human study and it negates the need for some laboratory animal experiments.

”Most people researching ageing are actually researching disordersassociated with ageing such as frailty, osteoarthritis and Alzheimer’s, for example. The aim is to deliver a better quality of life rather than some miserable immortality”

Generally, with notable exceptions, animal life is proportional to size, with tiny mammals surviving only a couple of years and us larger animals lasting for decades.  With dogs themselves, it’s generally the other way around though.

The 1999 multi-breed study by the Animal Health Trust found that, again with exceptions, smaller dogs tend to significantly outlast larger breeds.  In fact the short-life expectancy of many breeds is shocking to many people.

The Kennel Club is inching in the right direction, but one might hypothesise this is largely under continuing pressure from the paradigm shifting BBC docuxposé “Pedigree Dogs Exposed” aired in 2008.

For us dog fanciers, dogs contribute so much to society already; from companionship to finding people in avalanches or earthquake building collapses.  From assisting people with disabilities to protecting us at airports by sniffing out people with explosives and other bad guys.

Most recently, it has become evident that dogs can help with human health too. Dogs can most assuredly detect certain diseases with their exquisite sense of smell and, ironically, they encourage exercise and activity in people; activity being the anti-ageing therapy with the very strongest evidence base of all!

A small increase

So now, they are helping us to develop drugs to increase our own longevity and for this, their reward will be, potentially, a small increase in their own life spans.

Let’s not kid ourselves this will be some sort of advance for canine health though.  In mouse studies, really large doses of rapamycin increased longevity by about 9% for male mice.  Perhaps we can hope for an increase of 5% or more in dogs?

To us humans, a 5% increase could be a really big deal, a few years of (hopefully) happy healthy life. …but to dogs? Well consider the poor old Irish Wolfhound.  Median life expectancy 6.2 years. Increasing this by 5% equates to just a few months.

The Emperor's New Dress: #thatDress: A Case of Crowd syndrome?

The Emperor’s New Dress

If I were a clever writer, sadly I know I am not, I would write a parody blog providing scientific neurosciency explanation for why the King’s New Clothes do actually exist and simply cannot be seen by some people, but can be seen by others.  The kind of twine that is used is of a sufficient luminosity that some people simply fail to see it and despite the fact that he is really properly clothed, to some people he appears butt naked.  But Emperor's New Clothes is a very old phenomenon and that is exactly what has happened here.  I would have been the little boy that cried out from the crowd.. “but he’s naked!!”… and, I daresay, would have been dragged off and beheaded.  Hopefully those days are over, because here is my piece on #theDress #DressMeme.

Yes OK, I confess, I’m afraid this is yet another blog about the dress. I find whole phenomenon fascinating.  It is hardly surprising that someone who teaches the neuroscience of the eye, the visual cortex, rods, cones and opsins etcetera finds this phenomena interesting. However maybe you will be surprised at my perspective on the whole dress meme thing.

So let’s start with a summary of the facts (I think this is how Clouseau would begin in the Pink Panther movies?):  There is a dress apparently made by Roman that is black and royal blue. But a photograph of this dress has appeared where the colours are distorted and it looks gold and white or gold and pale blue.  Some people looking at the golden pale blue dress photo say that they see a black and royal blue dress. …and the internet has gone wild.  Scary.

There is also some confusion.  The question is not what colour is the dress, we know that in the high street store it is blue and black and it has just shifted colour to produce a funny coloured photo.  The squabble is that some people say that this specific picture looks blue and black.  There is no mystery about how digital photos of objects look different to the original, colour balance, colour temperature, exposure all explain that merrily.  The question is why some people say the gold looks black in this specific photo.

In response to this one scientist after another has trundled in to talk about perception differences between people, about the science of rods, cones, opsin proteins, wavelengths of light, processing in the visual cortex etc. but none of these “scientific” explanations explain the phenomenon.

My line is that the whole thing is nonsense.  It is probably a case of the “King’s New Clothes”.  There are a number of possible explanations from hoax to hysteria, otherwise known as “crowd syndrome”. If it is a hoax then how many how come so many people are a part of it? Well they aren’t really. My explanations are of hysteria, gullibility, or possibility sense of humour coupled to an innate sense of mischievousness in humans.  My only amazement is how few people can see the obvious flaws in the logic of the so-called scientific or visual perception anomaly theories.

Now why am I so confident that this is not a phenomenal about rods and cones and differences of perception? Because you can analyse the picture in heavy-duty imaging software and just get a simple answer on the RGB (Red, Green, Blue) levels of each portion of the picture. It’s true to say that when I see purple what registers in my brain maybe quite different from what you see when you see purple, but the problem here is that on a computer screen the world is less ambiguous.  “Black” in a digital photo means something quite specific.  It means that the RGB levels are either 0,0,0 or just close to this. For info, a typical digital photo consists of an array of pixels each with an RGB colour mix and each R, G and B value has to be a number between 0 and 255.  If they are all 255 that is pure white (255,255,255) and if we have black we have (0,0,0).  Of course (1,1,1) looks black and it gets less black as you move further away from (0,0,0). So there are a number of points around the RGB envelope that look black.  For example, below I have shown two very dark swatches. To me 40,40,40 looks pretty black. However, here’s the rub; we can analyse the gold in the photo and what do we get?

The figure shows the photo in question: and alongside it a swatch (A) coloured in the same colour OBJECTIVELY measured from the square using ImageJ software (NIH).  B and C are just examples of darker fills.  Below are three panels with the red, green and blue components separated, again in ImageJ, and the levels histograms from these presented below each.  For the record, the "blue/white" part is (126, 137,178).  There is no black guys.

So perhaps some people see 133,099,060 as black (“A” in the figure)?  …and always have… OK that’s possible, but that would mean they always would have done.  But millions of people have been viewing millions of gold dresses for years and how come no one spotted that gold looks black to some people before? It’s implausible. …and if it is true, well they are just colour blind in someway not observed previously.

Frequently optical illusions do occur, for example, running one colour, alongside another colour can give create an illusion that the second colour is different to its true colour. But you can “work it out” using objective analysis software (ImageJ et al.) as described above. Example: In theory… the red squares on the left look darker than those on the right? 

But are they? Simply analyse them in ImageJ:



Left:

Right

Histogram analysis shows that the mean colour intensity is 180 in both cases.  They really are identical. 

So since the digital photo clearly has no black in it what are the other explanations:

1. Confusion. People have seen that the original dress is really black and they are making the classical exam mistake of NOT answering the question. The question is not “what colour is the dress?”, the question is “what colour does the dress appear in this particular digital photo?”.
2. Crowd syndrome.  People are going with the flow.  Some people will be prepared to say what they think they should say, what they think the crowd expects them to say, to an extraordinary degree.  If we have an interview situation about this dress, with the interviewer asking what colour the guests see, s/he will be embarrassed if no one says black.  So some people will inevitably just have to throw a life line by saying it looks black to them, even though it doesn’t.
3. Sense of humour.  Well we are all having fun aren’t we, and that will require some people to perpetuate the myth by saying that the gold parts of the photo appear black to them.  Or the fun would stop.

…but visual illusion it isn’t :-)

Of course if 10% of sighted population do see 113,99,060 as black they will think this a really embarrassing diatribe.  Such is life.  I’ve done worse. There was even that one time……