Science

A comment on: Eat, fast, and live longer

A BBC Horizon programme presented by Michael Mosley. This programme explored the role of diet and nutrition in ageing.

At Cornell University researchers are studying a genetically modified mouse strain, which exhibits longevity (longer life) with a calorie restricting diet. This work has been extended to human study at Fontana Washington University. Here, they have set up a long-term study of dietary intervention. The principal investigator was quite confident that the people undertaking this approach are a new species. I doubt this very much. Participants are restricted to 1,900 calories a day, usually eaten at breakfast as a huge bowl of fruit. Time will tell if this approach does indeed lead to a longer life, but if positive results were needed, age-related tests were conducted. These included assessment of balance and reaction times, as well as blood tests for metabolic markers, and levels of body fat. Mr Mosley’s assessment was pronounced as ‘not good for his age’, but the balance and reaction time tests are both subjective and can be improved with practice. More alarming was the absolute declaration that following the calorie restriction programme for just one year will result in a reversal of disease progression. In fact, the researcher went on to say that after following the diet for 10 years, J (a volunteer) would never develop a stroke or heart attack.

The truth is that in order to fully assess the risk of death from cardiovascular disease or cancer, we would need to sequence every bit of DNA in every person in the world, follow those people from birth to death, and analyse their lifestyles for diet, exercise and environmental factors. Then, we might be able to say who will die from heart attack, or not. Some research, including my own, has identified important genes, which contribute to the risk. I have also found out that the normal variation of these genes, interacting with certain environmental factors, like stress, injury or infection, can affect the way the body responds. So, you see, it is a very complex picture, and not simply down to calorie restriction.

Professor Valter Longo, from the University of Southern California does add some science to the discussion. His research centres around an important metabolic protein, Insulin-like Growth Factor 1 (IGF1). Reduced levels of IGF1 in the blood have been associated with slowing cellular metabolism (the so called ‘go,go’ mode), increased repair of DNA damage and protection from age-related illness, in a genetically modified laboratory mouse strain.

Ex vivo research (that is, in cells taken from the animal’s body) have shown that cells in ‘go’ mode are more susceptible to cancer, as they do not show efficient cellular repair. Studies in humans have shown that calorie restriction together with a low protein diet leads to reduced circulating IGF1 levels in the blood. The mechanism of action for this is that as glucose (blood sugar) is depleted in the body, the body (in particular the large muscles) start burning fat for fuel. The liver stops or slows production of IGF1, pushing the cells into repair mode. This is not a happy state of affairs for the body of an active man or woman. Prolonged fasting can be dangerous and should only be done under medical guidance. Extreme metabolic changes can occur with short fasting protocols too. Proponents of the alternate day fast or the 5-2 fast regimes often report that they are unable to exercise on fast days due to dizziness and weakness.

The main tenet of the piece is portion control, which I endorse. It’s no secret that if you eat less and move more, your body will be stronger and healthier, provided of course that you maintain adequate nutrition. And the emergence of these fasting diets for sustained weight loss should be viewed with some skepticism.

There was no discussion about the role of our genetic make-up and ageing, or longevity. Yet, many of us will know people who live long and when asked the secret, simply say eat well, exercise a bit, and have fun. Sounds good to me.

Cereal Killers

Last week, research scientists sent an open letter to a group of activists called “Take the Flour Back” imploring them not to damage and destroy a field in Hertfordshire during a day of “planned action” at the end of May. The field is part of Rothamsted Research’s study into a genetically modified wheat which, it is hoped, will be highly resistant to aphids. A crop, which if successful, could eradicate the need for pesticide use.

Which is a good thing right? Well clearly not according to some.

We’ve been tinkering with the science of genetics for thousands of years, it’s almost as old as agriculture itself. Wheat, the most widely grown crop on the planet, is already a hybrid of many different species. Commercially grown modern wheat, untended, wouldn’t even survive in the wild; human beings have changed it beyond what would ever appear naturally. The grains are a lot bigger than undomesticated varieties and it has a real issue with seed dispersal, an impotence which has been cultivated through years of selective breeding: so it’s easier and more worthwhile to harvest. We’ve also bred in “dwarfing” which means the stalk is shorter, so the energy of the plant can be more usefully diverted to the production of seed. Trying to grow it in the wild would be the agricultural equivalent of releasing a sausage dog into the wilderness and expecting it to survive. All the aspects that make the dog desirable to us – in this case resembling a tiny-legged-sausage-with-a-face, would be exactly the things that would give it no chance. It is as far from a wolf as it’s possible to be – because that’s how we want it. But to most of us it’s not a dangerous abomination, it’s just a sausage dog.

So what has inspired such promises of violence towards a field of GM wheat? After all, since the late 90‘s when the widespread commercial use of GM crops started in the US, there has never been a single proven case of anyone ever having suffered ill effects through their consumption. All those millions and millions of people and nobody’s grown another head or a third armpit. Presumably because extensive trials, like the one under threat in Hertfordshire, are carried out to ensure the product is safe. GM Crops undergo a far more rigorous process of regulation than their non-GM equivalents and have since the very beginning.

“Take the flour back”, have suggested the threat of contamination, but that doesn’t really ring true. The safety measures in place for this particular trial are impressive to say the least: the crop will be surrounded by inert fields far beyond the dispersal range of the wheat’s pollen, making the threat of contamination as effectively close to zero as it is possible to get.

It’s difficult to understand the mindset of a group, whose concerns regarding GM include the fact that not enough research is being done, destroying that very same research. Protesters often cite the dangers of corporate oligarchy – control and profit, as a reason against GM crops, and whilst this is a very valid reason for scrutiny and where my own concerns normally lay, it doesn’t apply here either: the end-product, if successful, will not become a patented biocrop only available to the highest bidder. Despite all the doom-mongering, Rothamsted Research is not a malevolent multinational, hushing up mutants in it’s basement, it’s a group of well respected scientists whose aim is to improve on what we have and share it with the world. Their ultimate aim is a crop whose yield, resistance to drought, nutritional value, shelf-life and cost to grow could help end starvation in the Third World.

When I hear people say that we don’t know the results of long term use, that we’ve only been using GM crops for 20 years, I think to myself – that is considerably longer than millions of Africans are currently living. With around 15 million children dying of hunger every year, destroying this important work is destroying a manifesto whose ideals would wipe out famine.

In keeping with the subject of mutation, the word “activist” is one whose meaning has perhaps mutated as much as the crops some seek to destroy. In this instance though it is a moniker that seems destined to ring true. Rather than the admirable mission of concerned citizens, activist is now the “go-to” word to describe any campaigners associated with some degree of violence or destruction. I’ve felt for as long as I can remember that this is exactly the wrong thing, as a protester, to do. As soon as you become a crusader with the mindset of a terrorist, then you sacrifice, not your ability to be noticed, but your ability to be taken seriously, it dilutes the purity of your message. The role of a protester is to engage sympathy through peaceful actions, to shine a light on inequalities or dangers and thereby expand your audience. Once this has been achieved you voice valid points to that audience – be they the community, the government or the world.

You raise your voice, not your fist.

Gross Anatomy

I went to Medical School in 1987. It was an incredible experience, crammed full of learning from inspirational Professors at the peak of their careers. My stand-out memory is the first day of Gross Anatomy. Faced with dozens of cadavers in shrouds, fresh-faced students in crisp, clean white coats, and that smell – I couldn’t wait to get started. Such a privilege.

Each precious body had been donated to medical research, to help train doctors, nurses and physiotherapists. We stood next to our allocated body, four students in a group, and recited a modified Hippocratic Oath. We were to dissect the body over the academic year, 565 hours of dissection, in detail, covering all organ systems, blood vessels, nerves and the brain. Our bible for the year was Man’s Anatomy by Tobias and Arnold, in three volumes. Professor Tobias and Professor Arnold were the big beasts of Anatomy. We were in awe of them. They were known affectionately as PVT and JCA (behind their backs of course)!

Getting started was a hand-trembling affair, guided by this illustration. Skin preserved in embalming fluid is very tough. But once you’re in, you’re in – and the delights of the human body were ours to explore. Over the weeks and months, we committed to memory all the arteries, veins, nerves and bones (oh, my poor parents had that box of bones in their living room); using mnemonics to remember the long lists. For example, Peter And Paul Masturbated So Much Their Balls Shrank refers to the branches of one of the thoracic arteries (I wish I could remember which one)! I can remember, though, that this one refers to the twelve cranial nerves: Oh Oh Oh To Touch And Feel A Girl’s Vagina Very Happily (or something very like it). The point is, we were drunk on anatomy for that year. We were walking encyclopaedia of lists of body parts, our text books were marked in wax pencil (I still have one I used in 1987), and nobody would share the lift with us because the smell permeated our clothes and hair. We knew it and we didn’t care. We were doing something that not many people ever get to do. It would shape our lives in the future. Some would go on to be world class surgeons, some physicians, sports scientists, pharmacists. I decided on a career in research.

Who knows how a career will turn out. I didn’t even do Science at school. I was expected to study Languages at University. I’m grateful to a Biology teacher for showing me something different, and changing my life. She asked me to help her clear out the cupboard in the lab. What we didn’t find in there. And lurking at the back, in a dark jar, was the most gorgeous pig foetus. We changed the preserving fluid, to reveal the tiny, perfect animal; when was he put in there, kept for me to find? I was hooked.

And so, standing in the dissection hall, several years later, in the basement at Medical School, I knew I was in the right place. I grasped the scalpel with both hands and made the first cut. Nine months later, the Technician was standing over the cadaver we had been working on. It approaching the final Lesson – the brain. He used a tiny, whirring saw to remove the cranium. He revealed a clean, shiny brain in situ. In order to complete the study, we had to remove the brain, with all the cranial nerves in tact. I had the smallest hands and I put them on either side of the brain, inside the skull. I tugged gently and felt around the base of the brain, to free the nerves from their restraints. A little more tugging, and I had the brain in my hands. We prepared the dissection and made 1cm slices through the brain, sectioning it in cross-section. I have never forgotten that moment. And neither will countless other medical students. That brain, sectioned, preserved and displayed can still be seen in the Anatomy Museum at Wits Medical School.

Gross anatomy? I don’t think so. Stunning, wondrous anatomy, is more like it.

Ethics and Consent in Research

In general terms, we expect that people who ask our permission, who require our consent, will have the morals and ethics to respect our wishes and do the right thing. Recently however, I have seen a few examples where, frankly, the people concerned have the morals of a snake. I’ll say no more on that, but it prompted me to think more widely about these terms; ethics, morals, consent, permission.

In my own field of life science research, no research may be undertaken without a prior favourable ethical opinion. It used be ethical approval, which implied that a peer-reviewed process had taken place, and an important group of senior people had carefully considered the application and deemed it ethical to conduct the research. Now, it simply means that a committee has spent a few minutes of the agenda discussing the merits of the work, and no responsibility or blame can be put their way should the experiment turn out not to be ethical, either in its design or in the outcomes. A matter of semantics, perhaps, but important none-the-less.

Important because many of the subjects for my research are human volunteers who trust us, the scientists, to do the right thing. Now, I don’t want to put anyone off contributing to a research project; we do still need to do research using human subjects. But I do want to point out that the administration of the rules is not what it should be. To my knowledge, there is no enforcement of the consent. I have seen inspections. I have seen paper records. I know that biological material collected years ago is still lurking in the bottom of freezers in research laboratories. Consents and research records belonging to PhD students who have long-since moved on lingering on dusty bookshelves in study rooms. There is almost no way of knowing which material should be destroyed, ethical opinion and consents having long-ago expired. And that’s just in small university laboratories. Surely in large pharmaceutical and biotech organisations the record keeping and ‘policing’ of the research consents is more robust?

Well, yes it is, and that results in a different problem. Large organisations who embark on long term research require consent from participants to be able to follow up on the outcomes of the research over a very long period of time, decades in some cases. With changes in technology, particularly in genetic research, where even five years ago the cost of this work would have prohibited it, that is no longer the case. Cost are down, through-put is up. In short, scientists can analyse more data, more quickly, at much lower costs. If the material already exists, if the methodologies are the same, there are also no start-up costs. Results could be coming within days. That means that if you volunteered ten years ago, donated a tube of your blood, approximately 10ml, and gave scientists permission to keep cells, plasma and DNA, they will still have all those bits of you in storage and on file.

I mentioned genetic research, for this is where I am most concerned. When you donated that small amount of blood all those years ago, you were probably young, in your twenties (most lab volunteers are), and too young to be showing any sign of disease. Your parents would have been young too; too young in most cases to have cancer or heart disease. You wouldn’t yet have had children either. And now, what if you are told that scientists have just worked out that your DNA shows a variation recently found to be associated with cancer – would you want to know? What would you do about it? Cancer cannot be treated if it hasn’t formed a tumour yet. This is the proposal of researchers, owners of these so-called ‘bio banks’, because original research is too expensive and largely unfunded. Would you still give your consent for your material to be used?

I believe that material collected more than five years ago should either be destroyed or re-consented. Yes, that will cost money, but it keeps science honest and transparent. It makes sure that scientists’ personal ethics and morals are not tested. It introduces a check that the material we think is there, has been stored correctly and will be useful in the research. Very often, biological material degrades over time and is useless. Better then to destroy it.

And finally, I must reveal here that I never allowed my cells or DNA to be stored. I have never used my own blood, cells or DNA in any experiment I have conducted. I do not want to know that I have a particular genetic variation. Until scientists are clever enough to re-program my genetic material, there are some things not worth knowing. Of course, there are some conditions for which there are extremely good genetic tests, and with the correct counselling, it is very helpful to do these tests. But these tests have made the transition from research to clinical application. We can’t change what has gone before, but we can make sure that we are informed about the future. Research must be done, human biological material must be used for research wherever possible. Don’t take ethics, morals, consent and permission for granted in science, or anywhere else for that matter.

Not Sitting on the Fence

Animal experimentation is always a sensitive subject, whichever side of the fence you sit. When I started out in medical research, almost twenty-three years ago, animals were used in all sorts of experiments, from radical surgical therapies to shampoo testing.

I personally witnessed some horrors in the name of science. It was fascinating stuff though, particularly the work done on developing novel surgical strategies for strokes, heart attacks and bone regeneration after motor vehicle accidents. I can’t say that I enjoyed seeing rabbits being used to test shampoo or make-up, and I’m happy that this rarely happens these days. I fully support campaigns against animal testing.

But, I also support those pioneering scientists who over the years have used animals big and small to test their hypotheses and make huge strides in science and medicine.

For example, life-saving surgery performed daily in many hospitals, putting a stent in a coronary artery, a main blood vessel supplying the heart, following a heart attack, would not have been developed if not tried in animals first. This surgery saves hundreds of lives every year. People who go on to live very productive lives after heart attack. Surely this is a good thing?

More recently, I have seen groundbreaking work carried out in genetically modified mice. These mice have been bred without a particular receptor (simply put, this is a grabber for chemicals such as drugs), which is believed to be key in addiction. This work describes how people are genetically pre-disposed to becoming addicted to cocaine or heroin. And it will help to provide strategies for treating a lost generation drug of addicts across Europe. The cost benefit of this treatment runs to millions of Euro’s.*

There is sometimes an argument for using alternatives to animal testing. I always prefer to use non-animal experiments. In fact, I have not worked with animals in twenty years, preferring instead to recruit human volunteers for my research. This is more difficult than it sounds. It often involves drawing repeated small amounts of blood from which I prepare DNA, the genetic material of life. And volunteers are understandably concerned about what scientists might do with that information. Consent is not required for animal experiments.

But ethics is required for types of experimentation. Morals and standards on ethics are required at all times. Public scrutiny is key to this as well, which is why I think it is important to talk openly about the work we do on animals. It is not sufficient to say that a committee of academics and vets approved the work, therefore it’s OK to do it. No, scientists must be called to account at all times.

The scientists who do this work conduct their experiments under the strictest conditions and scrutiny. Far from being hidden away, animal experimentation is a transparent necessity of science. The public has the right to know what experiments are being done in their name.

The problem is that there are some people who are so passionate about not using animals for science and research, that they endanger the lives of others. And that means that we cannot always talk about it openly. It’s a conundrum to which I don’t have a solution, just a plea to both sides. Maintain a dialogue, keep an open mind. Be respectful of each other. Scientists, especially in the UK, who use animals in their research are not evil people, taking over the world. I admit, there are less scrupulous researchers in other countries, but here in the UK, animal-lovers and concerned campaigners should be re-assured that the work is done with the very best intentions, in the best facilities, under the tightest regulations and conditions.

The sad fact is, that animal models are still needed for progress in many human diseases. Whilst it is true that whole animals such as mice or rabbits do not adequately represent the whole body situation in human beings, animal organ systems and cells are extremely useful for science and research. Non-animal models such as immortalized cell lines derived from humans, can only answer one question at a time, because these cells are taken outside the body and are not subjected to the same complex environment.

My mother died of cancer. She died from a form of lung cancer, for which there is no cure. She was sixty-six years old. She was too young to die. If scientists wanted to test drug, or design an experiment to better understand the disease, I would be all for it. Wouldn’t you?

*Note: please understand that I cannot describe experiments in detail or identify scientists here.

For the Love of Knowledge

Education is the most powerful weapon which you can use to change the world. -Nelson Mandela

Nelson Mandela by Yousuf Karsh

I am often asked why I left South Africa, and 16 years on and I honestly don’t remember the exact reason. I know my husband and I were fortunate to receive an excellent education in South Africa and attended University there too. We wanted to be citizens of the world, to use our education where it was needed. I’m pleased to say that for the most part, we have been successful in this. No matter what happens in life, nobody can take away your education.

Thandulwazi* means for the love of knowledge in Zulu. Wouldn’t it be great if all pupils could go to school with those words in their hearts? Instead, as the post-grad assigned to supervise them, I see students in the final year of  their science degree, who are working so hard to complete coursework, study for exams and write a dissertation, that they seem to have forgotten that they chose science for the love of knowledge. They started university full of excitement and promise and over the three years have been worn down to just wanting to get a 2:1. Some, of course, will always be enthusiastic and will want to know more than the syllabus dictates. They are challenging and fascinating people.

I had a brief exchange with Erika-Check Haydn, from Nature News, about the challenges UK universities are facing as they attempt to produce biomedical scientists equipped to face the changing environment of research. They are only just up to speed with basic molecular biology techniques. Now, the technology companies are saying we need to train bioinformaticians. These are scientists who will spend their post doc jobs sitting at a computer, nowhere near a lab, analysing millions of digital data points. Where’s the thandulwazi in that?

So much of the data produced in experiments today is digital i.e. there is no physical picture of the result for us to examine.The peer-review process of publication in reputable journals should be able to put the data through the ringer, but sometimes the work is so specialist it can be difficult for outsiders to follow. The very nature of digital data is that it can be amended. The pressure to publish is a constant threat to researchers, and it can mean that research questions may not be stringently tested. I’m not saying that is what happened in the following examples but, questions will be raised if the data cannot be reproduced independently. While 2011 saw some incredible scientific breakthroughs, from the colour of meteorites to the secrets of aging (in mice, at least), it also saw two low points in science reporting.

Two research papers are in question at this time. The first is the finding that a murine leukaemia or related virus (MLV) was detected in patients with chronic fatigue syndrome. However, as the number of samples was limited and the data not reproducible, the authors had no choice but to retract their publication. That’s not to say they aren’t right. They simply need to find another way to prove it to their peers.

The second paper is more topical. Its focus is stem cell lineage and it was published in the journal Blood. The researchers acknowledge that some of the data may not reflect the published data analysis. This paper, was published in 2008 and cited 13 times in other papers. It could be argued that although there were errors in assembling the manuscript for publication, the authors stand by their findings and the interpretation thereof.

So, where does that leave the rest of us, struggling through to try and publish our blood, sweat and tears? I think it leaves us a little tainted in the public eye, and we must work harder to make sure our science stands up to rigorous scrutiny by our peers. As research funding decreases, the strongest research questions and protocols will rise to the top. Let’s hope that exciting research, and the love of science, does not drop away altogether.

*The St Stithian Foundation was set up to provide support for a Saturday school called Thandulwazi for pupils struggling to find a way complete their school education. It also supports teacher training. The Thandulwazi Trust is a Maths and Science Academy based in Johannesburg, South Africa.

Quantum Mechanics for dummies, and why I am stupider than I thought.

Science is interesting, and if you don’t agree you can fuck off.’

Richard Dawkins

‘I think I can safely say that nobody understands quantum mechanics,‘ said American physicist Richard Feynman in 1965. Mancunian TV-friendly, mop-haired, keyboard fingering, science teacher Professor Brian Cox tries to explain it anyway to an audience full of familiar entertainment faces, in a one-off BBC presentationA Night With The Stars from the lecture hall of the Royal Institution of Great Britain.

Rather than the eponymous cat, the example object in the box is a rough diamond – a million pounds’ worth of uncut precious rock – or rather its tightly packed carbon atoms. Through this example, Professor Cox seeks to enlighten the assembled celebrities and viewers of the perplexing world of Quantum Mechanics. I can’t speak for the celebrities, but I came away feeling like I knew less than when I started watching.

You see, that’s the problem with quantum mechanics: It’s harder to wrap your head around than it would be to wrap an iron bar around a strand of hair. I’ve always found it intimidating, as it involves a degree of mathematics, lateral thinking and imagination in harmony that goes beyond my learning. Don’t mistake me; I’m no idiot – although after trying to crack quantum mechanics I have a hard time believing it – but the sciences were never my strong point, being of a more creative type. As an adult, I’ve tried to fill in the holes in my learning the best I can, and Professor Cox is an accessible enough presenter, but the subject is harder to approach than the most beautiful woman you’ve ever seen on a dance floor surrounded by dozens of guys better looking and more charming than you.

I’ve read A Brief History of Time by Stephen Hawking three times. I say that not as a boast, as the the second and third times were trying to get it to sink in. Biology and the science of evolution by natural selection fascinate me. Tell me a fact about dinosaurs and I’ll lap it up. But Fabric of the Cosmos by Brian Greene still sits on my shelf mocking me, and even after this show quantum mechanics continues to elude me.

Basically, for those who are unfamiliar with the workings of quantum mechanics – which is most people – it describes the behaviour of the very, very small, and how it can be used to predict the behaviour of the very, very large – stars and other such stellar objects. It says that sub-atomic particles travel in waves; that everything is related to everything else; and that it acts completely counter-intuitively to anything prior science predicted. Einstein himself said of it: ‘Marvellous, what ideas the young people have these days. But I don’t believe a word of it.’

The annual Royal Institute Christmas lectures are a popular form of scientific entertainment, in a similar vein to A Night With The Stars. They’re intended for children and young people, although enjoyed by adults too. Thus far, to the best of my knowledge, there has not been a lecture on quantum mechanics. I’m not sure that the subject can be boiled down to a degree where it is suitable for consumption by children. Or maybe I’m looking at it the wrong way and it’s complex enough for children to take in their stride. All I know is if you stop paying attention for a second it’s like you’ve turned two pages of a book over at once.

When I was a child, television’s go-to mad scientist was Johnny Ball, presenter of such programmes as Johnny Ball Reveals All. I’m not as familiar with current children’s television, but I’m guessing there’s no equivalent of this or How2, and that they are biased largely towards entertainment rather than education. If there were, perhaps I could build up to A Night With The Stars eventually, but for now I’m left still scratching my head.

Testing Treatments

Medical research is one of those areas where everyone thinks they know a little.  Images of lab rats, miraculous cures and money grabbing pharmaceutical companies compete with the day to day reality of patients and doctors trying to tackle illness.  A new edition has been published of a book that tries to shed a bit of light on to the subject.

Testing Treatments, by Imogen Evans, Hazel Thornton, Iain Chalmers and Paul Glasziou, is aimed at the informed patient and explains how new medical treatments are researched, and how that relates to the experience of the patient being treated.  The book strikes a tone that is halfway between academic text and pop science, and might seem intimidating to some, but the regular summaries of key points and personal stories mean that the reader will soon find themselves gripped.

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The book takes a long view over history, covering scurvy treatments in 1747 right up to cancer trials of the present day, advocating a partnership approach between patient and doctor, and includes calls to action for professionals, patients and policy makers to ensure that questions are asked and information is shared.  The reader is encouraged to look sceptically at the need for treatments and screening, and to try to see through marketing and media hype.

Ben Goldacre provided the forward to this edition, and the book continues in the spirit of his work – accessible without being over simplistic.  I would have liked to have more detail, but I’m not sure how that could have been achieved without losing the ease of understanding.  There is an extensive list of further reading and references at the back of the book for the reader who would like to know more, and I didn’t personally feel that the scientific knowledge was shied away from in the text.  Perhaps a scientist would disagree, but I went away feeling that I knew much more about the subject and that I would be a more informed patient.

The publisher, Pinter and Martin, provided me with a copy of this book for review in my personal capacity

Testing Treatments is available for £6.99 from Amazon