How to read health news by Dr Alicia White (Bazian)

crabsallover highlights, key points, comments / links.

Bazian is the company who trawl the newspapers for NHS Direct then write their perseptive commentaries on the health news articles. This is an unedited copy of the article. 

• 12/23/2014
•  5:09 pm
• 
  

If you’ve just read a health-related headline that has caused you to spit out your morning coffee (“Coffee causes cancer” usually does the trick), it’s always best to follow the Blitz slogan: “Keep Calm and Carry On”. On reading further, you’ll often find the headline has left out something important, such as: “Injecting five rats with really highly concentrated coffee solution caused some changes in cells that might lead to tumours eventually (study funded by The Association of Tea Marketing).”

The most important rule to remember is: don’t automatically believe the headline. It is there to draw you into buying the paper and reading the story. Would you read an article called: “Coffee pretty unlikely to cause cancer, but you never know”? Probably not.

To avoid spraying your newspaper with coffee in the future, you need to analyse the article to see what it says about the research it is reporting on. Bazian (the company I work for) has appraised hundreds of articles for Behind the Headlines on NHS Choices, and we’ve developed the following questions to help you figure out which articles you’re going to believe and which you’re not.

Does the article support its claims with scientific research?

Your first concern should be the research behind the news article. If an article touts a treatment or some aspect of your lifestyle that is supposed to prevent or cause a disease, but doesn’t give any information about the scientific research behind it, then treat it with a lot of caution. The same applies to research that has yet to be published.

Is the article based on a conference abstract?

Another area for caution is if the news article is based on a conference abstract. Research presented at conferences is often at a preliminary stage and usually hasn’t been scrutinised by experts in the field. Also, conference abstracts rarely provide full details about methods, making it difficult to judge how well the research was conducted. For these reasons, articles based on conference abstracts should be no cause for alarm. Don’t panic or rush off to your GP.

Was the research in humans?

Quite often, the "miracle cure" in the headline turns out to have only been tested on cells in the laboratory or on animals. These stories are regularly accompanied by pictures of humans, which creates the illusion that the miracle cure came from human studies. Studies in cells and animals are crucial first steps and should not be undervalued. However, many drugs that show promising results in cells in laboratories don’t work in animals, and many drugs that show promising results in animals don’t work in humans. If you read a headline about a drug or food "curing" rats, there is a chance it might cure humans in the future, but unfortunately a larger chance that it won’t. So there is no need to start eating large amounts of the "wonder food" featured in the article.

How many people did the research study include?

In general, the larger a study the more you can trust its results. Small studies may miss important differences because they lack statistical “power”, and are also more susceptible to finding things (including things that are wrong) purely by chance.

You can visualise this by thinking about tossing a coin. We know that if we toss a coin the chance of getting a head is the same as that of getting a tail – 50/50. However, if we didn’t know this and we tossed a coin four times and got three heads and one tail, we might conclude that getting heads was more likely than tails. But this chance finding would be wrong. If we tossed the coin 500 times - i.e. gave the experiment more "power" - we'd be more likely to get a heads/tails ratio close to 50/50, giving us a better idea of the true odds. When it comes to sample sizes, bigger is usually better. So when you see a study conducted in a handful of people, treat it with caution.

Did the study have a control group?

There are many different types of studies appropriate for answering different types of questions. If the question being asked is about whether a treatment or exposure has an effect or not, then the study needs to have a control group. A control group allows the researchers to compare what happens to people who have the treatment/exposure with what happens to people who don’t. If the study doesn’t have a control group, then it’s difficult to attribute results to the treatment or exposure with any level of certainty.

Also, it’s important that the control group is as similar to the treated/exposed group as possible. The best way to achieve this is to randomly assign some people to be in the treated/exposed group and some people to be in the control group. This is what happens in a randomised controlled trial (RCT) and is why RCTs are considered the "gold standard" for testing the effects of treatments and exposures. So when reading about a drug, food or treatment that is supposed to have an effect, you want to look for evidence of a control group and, ideally, evidence that the study was an RCT. Without either, retain some healthy scepticism.

Did the study actually assess what’s in the headline?

This one is a bit tricky to explain without going into a lot of detail about things called proxy outcomes. Instead, bear in mind this key point: the research needs to have examined what is being talked about in the headline and article (somewhat alarmingly, this isn’t always the case).

For example, you might read a headline that claims: “Tomatoes reduce the risk of heart attacks.” What you need to look for is evidence that the study actually looked at heart attacks. You might instead see that the study found that tomatoes reduce blood pressure. This means that someone has extrapolated that tomatoes must also have some impact on heart attacks, as high blood pressure is a risk factor for heart attacks. Sometimes these extrapolations will prove to be true, but other times they won’t. Therefore if a news story is focusing on a health outcome that was not examined by the research, treat it with a pinch of salt.

Who paid for and conducted the study?

This is a somewhat cynical point, but one that’s worth making. The majority of trials today are funded by manufacturers of the product being tested – be it a drug, vitamin cream or foodstuff. This means they have a vested interest in the results of the trial, which can potentially affect what the researchers find and report in all sorts of conscious and unconscious ways. This is not to say that all manufacturer-sponsored trials are unreliable. Many are very good. However, it’s worth seeing who funded the study to sniff out a potential conflict of interest.

Want More? ... then refer to the ...

Source: http://www.nhs.uk/news/Pages/Howtoreadarticlesabouthealthandhealthcare.aspx

Health benefits of holidays 'exaggerated'

reposted from: http://www.nhs.uk/news/2013/01January/Pages/Health-benefits-holidays-exaggerated.aspx

crabsallover highlights, key points, comments / links.

Mail Online bias!

Going on holiday really is good for your health... and the benefits last for months,' declares Mail Online, the website of the Daily Mail and Mail on Sunday.

Despite being listed in the "health" section of the website, the news is based on a report by Nuffield Health and Kuoni Travel Ltd. To more sceptical readers, the report may appear to be nothing more than an elaborate piece of marketing material.

If you were being hypercritical, this collaboration also arguably represents a financial conflict of interest so big you could see it from space.

The "healthy holiday" report bears little resemblance to a rigorous scientific study and has not undergone the peer review process, where independent experts scrutinise the methods and findings of a study. If the "research" had been subjected to peer review, it would almost certainly have been dismissed out of hand.

This small experiment involved just 12 people – half of whom were sent on exotic holidays, while half stayed at home – and tells us very little about the effect of holidays on our physical and mental health.

While its broad conclusion that holidays are generally good seems commonsense, we cannot read too much into this experiment because of a long list of methodological limitations.

Even if we do take the report's findings at face value, its results are less than impressive. In some cases, people actually experienced increased stress levels during their holiday and some gained weight.

What is depressing is Mail Online's willingness to take the report at face value, and its failure to inform readers about the extensive limitations of this "experiment".

Where did the story come from?

The experiment was carried out by staff from Nuffield Health (which runs gyms and hospitals) in collaboration with Kuoni Travel Ltd (a holiday company). While no funding source was explicitly stated, it appears to have been funded by one or both of the collaborating organisations.

The experiment was not published in a peer-reviewed journal and so has not undergone the scrutiny of independent experts in health or medicine. It was instead released as a brochure on the Nuffield Health website.

There is a substantial conflict of interest in a report like this, as both Nuffield Health and Kuoni stand to gain commercially from conclusions that support their respective core businesses of health and holidays.

While the Mail Online's reporting of the findings was accurate, what is worrying is what they failed to report – the significant conflicts of interest, the lack of a peer review process, and problems with the extremely small sample size. Although the story makes for a great feelgood headline, it could mislead many readers.

What kind of research was this?

This wasn't research in the way we would usually expect to see it: peer-reviewed, published in a journal and with clear methods. It is probably best to use the language of the authors and call it an "experiment", which is less scientifically rigorous.

As it has not been published in a peer-reviewed journal, this experiment has not been appraised by experts in the field. This crucial stage ensures that a study's conclusions are justified by the study design and findings, and allows for flaws in the research to be pointed out.

Without such a peer review process, the authors' conclusions may be mistaken and remain unchallenged.

What did the research involve?

The experiment recruited six couples and subjected them to a battery of clinical and psychological tests before sending three couples on a free holiday, while three couples stayed at home. It was unclear whether the stay-at-home controls had the equivalent time off work or if they continued working while the others jetted off.

Two weeks after the holidaymakers returned, more clinical and psychological tests were performed and participants wore heart monitors for several days. The Nuffield Health staff then reported differences in health and wellbeing measures between the couples who went on holiday and those who didn't.

Three holiday destinations involving different activities were selected to see if the impact of the type of holiday made any difference to health and wellbeing measures. One couple were sent to Thailand for an activity holiday, another couple were sent to Peru to volunteer, and the other couple went to the Maldives for a relaxing "fly and flop" holiday.

The six stay-at-home controls (three couples) were sought to match the lifestyles, age group, physical activity, and alcohol and caffeine intake of those sent on holiday. Controls underwent the same battery of physical and mental health assessments as the holidaymakers.

No randomisation or allocation concealment was reported in the study when assigning the couples to either the travellers group or those who stayed at home.

Statistical testing is also not reported, in order to compare the differences between the travellers and those who stayed at home. This is not a good approach, as it means that any reported differences may be due to chance.

What were the basic results?

The Nuffield Health brochure reported that having a vacation improved the holidaymakers' ability to recover from stress by 29%, while the ability of those who stayed at home deteriorated by 71%. Holidaymakers' sleep quality improved by 34 points, whereas stay-at-homers' sleep worsened by 27 points. Blood pressure was reduced in the holidaymakers by 6%, compared with an increase of 2% in those who didn't go on holiday.

Other reported improvements for holidaymakers included decreases in blood sugar levels, improved body shape, and improved energy and mood.

How did the researchers interpret the results?

The Nuffield report, called 'Revealed: how holidays help you live longer', stated that "taking the right kind of holiday for you may lower your stress levels, improve your resilience to stress, and therefore improve your mental and physical health".

Conclusion

This small experiment involving just 12 people (six couples) tells us very little about the effect of having a holiday on physical or mental health. While its conclusions seem commonsense, we cannot read much into this experiment for the following reasons:

Small study sample

Only 12 people took part in this study. Basing conclusions on the experiences of so few people is risky and unreliable. Studies on larger groups of people may reach different conclusions. Similarly, it is not clear how representative the 12 people in the study were in relation to the general UK population, as physical and mental health can vary with age, ethnicity and social background.

No statistical testing

There was no statistical testing performed in this experiment. This is a huge limitation. It means that we don't know whether any observed differences between the holidaymakers and those who stayed at home were actually likely to be real, or whether they are simply chance findings.

No allocation concealment

It is unclear whether the people who stayed at home knew they were taking part in an experiment on the effect of going on holiday. The knowledge that they weren't lucky enough to be sent on a free holiday, and were instead in the stay-at-home group, may have adversely affected their short-term health and physical measures.

Conflict of interest

Both parties in this report have financial interests in promoting the advice that holidays are good for your health, and that leading a healthy lifestyle helps you live longer. This may have biased the experiment design and reporting of the findings.

Not peer-reviewed 

As discussed above, without being published in a peer-reviewed journal and appraised by other leading experts, the authors are free to report and conclude what they wish. The peer review and publication process can add an extra layer of reliability and believability to research findings that are absent in this report.

The definite claim of the report's title – that holidays "help you live longer" – is completely unsubstantiated, based on the evidence the authors present.

The bottom line is that this experiment contributes very little to scientific research, but does reinforce the commonsense view that a holiday is generally a good thing, whether you are whisked away to a luxury hotel in exotic climes or a seaside chalet in Skeggy.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter.

Links to the headlines

Going on holiday really is good for your health... and the benefits last for months. Mail Online. Published January 29 2013

Further reading

Kuoni  & Nuffield Health. The Holiday Health Report 2013 – How Holidays Make You Live Longer (PDF 3.4MB). Published online January 29 2013

Food and cancer: why media reports are often misleading

reposted from: Cancerresearchuk

crabsallover highlights, key points, comments / links.

Food and cancer: why media reports are often misleading

Fri Dec 14, 2012 15:07 Share

This research shows the danger of overstating the results of single studies

The media’s appetite for things that cause or prevent cancer can be as notable for its sheer volume as for – in some cases – its hype. And food is a key area of interest, because everyone can relate to the latest headlines on bacon or broccoli.

Rarely a week goes by without headlines on the latest “cancer-busting” food or, at the other end of the spectrum, the unexpected perils of pop. So a research article with the intriguing title ‘Is everything we eat associated with cancer? A systematic cookbook review‘, published in the American Journal of Clinical Nutrition recently, couldn’t fail to catch our attention.

This review looked at a selection of cookbook ingredients to see if they had been investigated for links to cancer. The researchers found that most of the 50 foods they looked at had been associated with an increased or decreased cancer risk in the scientific literature.

But is this a testament to the power of different foods over our chance of developing cancer? Or is it proof that scientists just can’t make their mind up?

In fact it’s neither. The most important finding of the review was that single studies often found links that had only weak evidence behind them.

The research provokes thoughts about why we do research, how much one study on its own can tell us, and the value of considering the balance of evidence.

Perhaps most importantly, is also raises questions about how much detail scientists and the media provide as context when they present results to the public.

And rather ironically, and worryingly, one paper decided this study warranted the conclusion that there is ‘no proven link between foods and cancer’. This is clearly not the case, as we explain below.

What’s a ‘systematic cookbook review’ anyway?

The authors of this review – the first of its kind – picked page numbers at random from a cookbook, and used the ingredients they found to create a list of 50 different foods to investigate. The book (The Boston Cooking-School Cook Book) is over a hundred years old, but most of the foods on the list, such as olives, lamb, flour and mushrooms, are standard fare today.

The authors then used PubMed, a comprehensive database of published scientific research, to look for studies linking each of the foods to an altered risk of cancer in people. Of the 50 foods on the list, they found that 40 had been the subject of at least one study. The 10 ingredients that hadn’t been investigated were generally more unusual (terrapin, for instance).

Building conclusions on shaky ground

For each type of food, the authors then looked in more detail at the studies they’d found, picking up to 10 results, or choosing the most recent where there were more than 10 studies. They compared what the studies had concluded, with how strong their evidence was – and particularly how statistically certain they could be that their finding wasn’t just down to chance.

Almost three-quarters of the studies claimed that consuming the food in question affected a person’s risk of cancer, rather than making no or little difference. But in most cases the evidence behind these claims was either weak or simply not there.

Results that had at least weak evidence tended to be highlighted in study abstracts – the short summary presented at the start of the paper, which is often the basis for press releases and subsequent media stories – whereas the findings that could have been down to chance (i.e. weren’t statistically significant) were reported only in the full manuscript.

And a finding with only weak evidence behind it starts to look shakier if you discover it was the strongest result out of many – after all, a one in 20 chance of being a fluke is not very impressive if someone’s had another 19 goes. This practice of highlighting findings from subgroup analysis, as it’s known, can be particularly misleading, as often only the abstract of an academic paper is available free of charge.

The way studies compared the amounts of a food people ate also varied widely. Less than 1 in 7 of the studies compared people who didn’t eat a food with those who did. Instead they compared people who on average had different amounts, which makes it more difficult to work out if it is the specific food that’s having the effect. And similar studies, comparing the same food and same type of cancer, often used different ways of classifying people’s consumption, making it hard to work out if findings supported one another or not.

The balance of evidence

The overall balance of evidence is more important [than] single studies

Next, the authors looked at studies called ‘meta-analyses’, that pooled the results of other studies. These aim to calculate the overall size of a possible link between a food and cancer risk, and are considered by many to be ‘gold standard’ evidence. Though of course they are only as good as the data you put into them.

The authors found that links calculated in meta-analyses tended to be much weaker than the findings from the single studies. Tellingly, the meta-analyses were much more likely to conclude that a food didn’t make much difference to a person’s risk of cancer. This suggests that the single studies were likely to be overestimating any link they found.

But this doesn’t necessarily mean that the studies were pointless or even badly conducted. The foods we eat are a sensible factor to consider when thinking about cancer risk, particularly when it comes to cancers of the digestive tract, which most of the studies focused on.

But what this study highlights is the importance of the balance of evidence when considering the impact of a study. And alongside that, we need to consider whether there’s a reasonable way for a given food to influence cancer risk, or whether there’s another explanation for a potential link.

For example people who eat more healthily tend to take more interest in their health in general, which could help to explain any observation that eating apples keeps the doctor away.

As a whole, science is like an enormous jigsaw puzzle with every study contributing one small piece to the picture. Corners and easily identifiable parts of the image may seem like the most important – but you still need all those bits of sky. As the person looking at the puzzle, the key is to take in the whole thing and be aware of any gaps. This is how science works: each new academic publication doesn’t tend to cause wild swings in opinion – rather the slow accumulation of evidence allows the movement towards established fact.

But the popular media often highlights disagreement and controversy, so we need to remind ourselves not to read too much into a one-off claim.

So is there a link between diet and cancer or not?

Some of the foods thrown up by the cookbook search have been found to have clear links to cancer – but through decades of accumulated research, not isolated studies. Alcohol (wine, rum and sherry were on the list) is a well-established cause of cancer, and there’s a known link with eating too much red meat (lamb, pork, veal and beef) and with salty foods. On the reduced risk side, many of the foods considered were fruits and vegetables – getting your five a day is another good way to reduce the risk of cancer.

Despite a headline saying otherwise, this review definitely doesn’t demonstrate that there’s no link between diet and cancer. It just underscores the need for caution when interpreting the often limited evidence. So while it’s fair to say that broadly what we eat can affect our risk, in most cases we simply don’t have enough evidence when it comes to specific foods.

The message that the best way to reduce the risk of cancer through what you eat is to have a healthy balanced diet may not be new and exciting, but it remains the one with the strongest evidence.

Further reading

• The causes of cancer you can control
• Lifestyle and cancer: against the blame game

Reference

Schoenfeld, J. & Ioannidis, J. (2012). Is everything we eat associated with cancer? A systematic cookbook review American Journal of Clinical Nutrition DOI:10.3945/ajcn.112.047142

sample sizes in medical trials - how do you know whats good for you?

reposted from: http://plus.maths.org/podcasts/PlusPodcastFeb10.mp3 (a 30 minute podcast).

David Spiegelhalter talks (up to 5') about small and large sample sizes .. and number of deaths must be large in in medical trials to get a confident result! Also Randomised Control Trials (the 'gold' standard) allows

• fair comparison - no cheating
• differences just due to chance OR drug is effective

Also

• Statistical significance (16') eg 95% confidence level, confidence interval, 
• Nigel Hawkes absolute and relative risks (25'), benefits expressed as a % ... but risks or disbenefits are often expressed as numbers eg 1 in 2000 - which sound small. This is called 'mis-matched framing'.

Also read "Evaluating a medical treatment - how do you know it works?"

eg randomised-controlled trials

.... However, this still left the problem that if you wanted to rig (bias) the results to prove a treatment worked, you could preferentially give it to patients who were less sick, or give the older treatment to patients who were more sick. The solution to this, first used by the Medical Research Council in the 1940s for their study of whooping cough vaccines, is to randomly choose which patient is going to get the new treatment, and which is going to get the control (placebo) treatment.

Controlled trials with random allocation to the two groups became known as a randomised-controlled trials or RCTs. By randomising, not only do you end up with a balance of sicker and healthier patients in the two groups, you also end up with a balance between things you don't know about which may also have an impact on the patient's health and therefore the outcome of the treatment. Then — because, in theory, the only difference between the two groups is whether or not they received the treatment being tested — we can assume that any differences in outcome we observe are most likely due to the treatment and nothing else.

The randomised-controlled trial is the gold standard of clinical research and is now universally used to evaluate new treatments.

Health Check - how do you decide which research study findings to put into practise in your own life?

reposted from: Listen to the first 9 minutes of Health Check from BBC World Service: http://www.bbc.co.uk/i/p00c9yfg/

Using the examples of two recent medical studies; use of aspirin to prevent cancer and the risk of using mobile phones when you are pregnant, Prof. David Spiegelhalter (who I heard giving a talk on biomedical statistics & statins at the June 2010 Cheltenham Science Festival) said that the studies to give more weight to were NOT single study laboratory non-human trials done by one group OR multi-factor related trials but INSTEAD large scale, peer reviewed, randomised controlled, systematic reviews undertaken by an authoritive group who have looked at the totality of evidence from a large numbers of people over many years and whose paper is backed up by a wide range of independent scientists.

Science fact and the SENS agenda

crabsallover says "a group of 'representative mainstream gerontologists' critique the anti-ageing SENS agenda of Aubrey de Grey. This is a classic example of the intersection between science, pseudoscience, science fiction, the scientific method and what I call the 'Engineering defence argument'. The EMBO Reports article is posted below in full without edits except crabsallover highlights are in blue & key points in bold blue."

reposted from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1371037/?tool=pubmed

EMBO Rep. 2005 November; 6(11): 1006–1008. doi: 10.1038/sj.embor.7400555.

PMCID: PMC1371037

Copyright © 2005, European Molecular Biology Organization

Science and Society

Viewpoint

Science fact and the SENS agenda

Huber Warner,^a Julie Anderson,¹ Steven Austad,² Ettore Bergamini,³ Dale Bredesen,¹ Robert Butler,⁴ Bruce A. Carnes,⁵ Brian F. C. Clark,⁶ Vincent Cristofalo,⁷ John Faulkner,⁸ Leonard Guarente,⁹ David E. Harrison,¹⁰ Tom Kirkwood,¹¹ Gordon Lithgow,¹ George Martin,¹² Ed Masoro,² Simon Melov,¹Richard A. Miller,⁸ S. Jay Olshansky,¹³ Linda Partridge,¹⁴ Olivia Pereira-Smith,² Tom Perls,¹⁵ Arlan Richardson,² James Smith,² Thomas von Zglinicki,¹¹ Eugenia Wang,¹⁶ Jeanne Y. Wei,¹⁷ and T. Franklin Williams¹⁸

¹Buck Institute for Age Research, Novato, CA, USA

²University of Texas Health Science Center, San Antonio, TX, USA

³University of Pisa, Pisa, Italy

⁴International Longevity Center, New York, NY, USA

⁵The University of Oklahoma Health Sciences Center, Tulsa, OK, USA

⁶Department of Molecular Biology, Aarhus University, Denmark

⁷Lankenau Institute for Medical Research, Wynnewood, PA, USA

⁸University of Michigan, Ann Arbor, MI, USA

⁹Massachusetts Institute of Technology, Cambridge, MA, USA

¹⁰The Jackson Laboratory, Bar Harbor, ME, USA

¹¹University of Newcastle upon Tyne, Newcastle upon Tyne, UK

¹²Department of Pathology, University of Washington, Seattle, WA, USA

¹³University of Illinois at Chicago, Chicago, IL, USA

¹⁴University College London, London, UK

¹⁵University of Boston, Boston, MA, USA

¹⁶University of Louisville, Louisville, KY, USA

¹⁷University of Arkansas for Medical Sciences, Little Rock, AR, USA

¹⁸University of Rochester, Rochester, NY, USA

^aHuber Warner is Associate Dean for Research at the University of Minnesota College of Biological Sciences, St Paul, MN, USA.
Email: warne033@umn.edu

 See the article "Like it or not, life-extension research extends beyond biogerontology" in volume 6 on page 1000.

 This article has been cited by other articles in PMC.

Summary

What can we reasonably expect from ageing research?

•  Other Sections▼

In an article published in the EMBO reports Special Issue on Time and Ageing, Aubrey D.N.J. de Grey criticizes biogerontologists for what he sees as their generally pessimistic view of the possibilities for intervening in the ageing process (de Grey, 2005). In his view, “resistance [of biogerontologists] to debate on how to postpone ageing is delaying progress and costing lives.” de Grey believes he has formulated a research plan that, in his words, will “stop people from getting frailer and more prone to life-threatening diseases as they get older, and moreover [will] restore the already frail to youthful vitality”. Similar to vintage cars maintained by careful mechanics, individuals will then retain this happy state “indefinitely ... even at ages many times what we reach today”. In de Grey's opinion, “the failure of most biogerontologists to maintain an open mind concerning the scientific options ... [has] the result that much longer healthy lives are being denied those who will die before 'real anti-aging medicine' arrives.”

In the words of the great American journalist H.L. Mencken, “for every complex problem, there is a simple solution, and it is wrong.” de Grey's research programme, which he terms 'strategies for engineered negligible senescence' (SENS), involves a combination of preventative and therapeutic interventions (de Grey, 2003). To solve the problem of apoptosis in senescent cells, one simply uses “senescence marker-tagged toxins”. To cure cancer, one just calls on “total telomerase deletion plus cell therapy”. To prop up the failing immune system, one can turn on “IL-7 mediated thymopoiesis”. To reverse mitochondrial mutations, one need only use “allotopic [mitochondrial]-coded proteins” of the type favoured by algae. Cell replacement can be accomplished by “stem cell therapy and growth factors”, whereas retooling the endocrine system relies on “genetically engineered muscle”. Cleavage of glycosylation crosslinks will involve periodic exposure to phenacyldimethylthiazolium chloride, and so on. Yet, in his writings, de Grey fails to mention that none of these approaches has ever been shown to extend the lifespan of any organism, let alone humans.

The response to this farrago—“a confused mixture, or hodgepodge”—depends on one's perspective. Journalists with papers to sell or air-time to fill too often fall for the idea of a Cambridge scientist who knows how to help us live forever with telomerase, allotopic mitochondrial-coded proteins and marker-tagged toxins. To explain to a layman why de Grey's programme falls into the realm of fantasy rather than science requires time, attention and the presentation of detailed background information. In addition, anyone who is tempted to do so is easily cast as a Luddite, an enemy of creativity and noble ambition, and someone whose prissy reluctance to confront de Grey's ideas might prevent us from living forever.

Those who work in science or know a good deal about how science progresses understand how difficult it is to select, among many attractive ideas, the few that might actually pan out. It is equally difficult to follow good leads painstakingly, while avoiding false hopes, as scientific knowledge matures to the point where engineering ideas present themselves for test. Those among us who are immunologists recognize that the few tests of the idea that interleukin 7 (IL-7) can improve protective immunity have produced disappointing results so far. Learning how to integrate IL-7 into preventive medicine will take decades of hard work, if it ever proves to be useful. Similarly, those of us who work on cancer know that the inhibition of telomerase is one among many interesting ideas that might, one day, help to control some forms of human neoplasia. However, we also know that the ablation of telomerase activity might have serious side effects on stem-cell and lymphocyte function, might fail to work in some tumour types, might select for neoplastic cells with alternative ways to avoid growth inhibition, and has not yet been shown to prevent or treat cancer either in humans or in animal models. Genetically engineered muscle cells might one day prove useful as sources of needed hormones or systemic factors, but the use of such an approach to slow ageing, let alone to reverse it, must confront the plain fact that, at present, no one knows which hormonal changes might be needed, in what tissues and at what intervals, to accomplish such a miracle. As far as we know, “senescence marker-tagged toxins” do not yet exist. Moreover, if they did, it is uncertain whether they would do more harm than good. Most therapeutic ideas, even the most plausible, come to nothing—in pre-clinical studies or clinical research, the proposed interventions are found to be toxic or induce unwelcome side effects, are mooted by more successful ideas, or, most often, simply fail to work as hoped.

Journalists ... too often fall for the idea of a Cambridge scientist who knows how to help us live forever with telomerase, allotopic mitochondrial-coded proteins and marker-tagged toxins

Each one of the specific proposals that comprise the SENS agenda is, at our present stage of ignorance, exceptionally optimistic. Therefore, by multiplying the probabilities of success, the claim that all of these proposals can be accomplished, although presented with confidence in de Grey's writings, seems nonsensical. Consequently, the idea that a research programme organized around the SENS agenda will not only retard ageing, but also reverse it—creating young people from old ones—and do so within our lifetime, is so far from plausible that it commands no respect at all within the informed scientific community.

Each one of the specific proposals that comprise the SENS agenda is, at our present stage of ignorance, exceptionally optimistic

Deciding on priorities for scientific research requires the careful weighing of alternatives so as to assess their relative merits, possible weaknesses, anticipated rewards and costs. All of us who have signed this essay agree with de Grey that research into the basic biology of ageing needs and deserves more support than it presently receives. In our opinion, those who are in charge of deciding how research funds are allocated seriously underestimate the potential benefits of basic research on the causes of ageing in terms of public health. We believe that we have good solid arguments on these points, and ideas and evidence that deserve public hearing (Miller, 2002). The fact that the rate of ageing is malleable by evolutionary pressures, which can slow ageing dramatically by selecting among genetic variants in suitable ecological niches, provides a rationale for thinking that we might eventually learn how to postpone human illnesses to an important degree. Some of us feel that research on telomere biology deserves special attention; others would argue that studies of mitochondrial function merit high priority and still others believe that the evaluation of antioxidant defences might be fruitful. We are all familiar with the unambiguous evidence from numerous laboratories showing that ageing can be slowed sufficiently to increase longevity by 30 or 40% in mammals. Moreover, we believe that learning how to do similar things for humans might lead to impressive improvements in public health, with extra decades of active disease-free lifespan as a plausible, although by no means certain, goal. Some of us are moderately optimistic that present ageing research will have therapeutic implications, whereas others are less optimistic on this point. None of us, however, believes that plans to 'engineer' the body to prevent ageing indefinitely or to turn old people young again have the remotest chance of success. Although it is foolhardy to try to 'prove' that a particular engineering problem can never be solved, we can and must insist that speculation based on evidence be discriminated from speculation based on wish fulfilment alone, and recommend that research programmes should be based on fact and extrapolation from earlier successes and failures.

...those who are in charge of deciding how research funds are allocated seriously underestimate the potential benefits of basic research on the causes of ageing in terms of public health

Selecting the most promising lines of scientific investigation from among many possibilities is the key to doing good science. It is the hardest thing that a graduate student or postdoctoral fellow has to learn, and many never do. Each successful investigator knows, from hard experience, that his or her 'hit' rate—the proportion of ideas that leads to major discoveries—is relatively low. Each idea that we decide to pursue will cost years of work and a great deal of money, so we spend a lot of time—at meetings, seminars and in the library—trying to search for and weigh alternatives, and looking for loopholes in our chain of arguments before they are pointed out to us either by peer reviewers or experimental results.

Short-circuiting this process of critical, sceptical selection among research priorities—presenting buzzwords as substitutes for carefully selected and testable hypotheses about ageing and its control—might be clever marketing, but it is a poor substitute for scientific thought. Presented by an articulate, witty and colourful proponent, a flashy research agenda might catch the eye of a journalist or meeting organizer who is hunting for attention, publicity and an audience; however, the SENS agenda is easily recognized as a pretence by those with scientific experience.

When does such a promotion campaign make the transition from an amusing eccentricity to an obstacle to scientific progress? Ageing research is a discipline that is only just emerging from a reputation for charlatanry. Indeed, those who represent themselves as vendors of amazing miracle cures for ageing are more numerous, and attract far more public interest, than those who carefully research the causes and potential retardation of the ageing process. This has implications for the pursuit and funding of research. Although politicians know that they can earn votes by promising cures for cancer and AIDS, a politician who was rash enough to campaign on a pledge to slow the ageing process would be judged as lunatic. This is unfortunate, as many of us who work on ageing believe our work is likely, if properly supported, to produce improvements in public health at least equal to those that would come from a vaccine for AIDS or a cure for cancer. Nevertheless, we are gradually—much too gradually—gaining the respect and attention of pundits, journal editors, peer reviewers, scientific administrators, and even the occasional politician who is willing to consider the implications of our research for preserving health and postponing disease. From this hard-won perspective, we are concerned when we see scientific journals and meetings give space and attention to empty fantasies of immortality, artfully camouflaged under the guise of research proposals.

de Grey's most recent challenge takes the form of a chiding lament over the resistance of mainstream biogerontologists to 'debate' his plan on its merits. On its face, this appeal earns sympathy points. Who could be opposed to a free exchange of ideas? What authoritarian Philistine would endorse censorship or the quashing of different points of view, no matter how odd they might seem to contemporary conservative opinion? Surely the publicity drawn to ageing research by the SENS/de Grey juggernaut will, in the long run, draw attention to, and support for, all forms of ageing research through a kind of 'trickle-up' mechanism? Why not simply debate with de Grey and let the most convincing arguments win? It is, however, our opinion that pretending that such a collection of ill-founded speculations is a useful topic for debate, let alone a serious guide to research planning, does more harm than good both for science and for society.

Short-circuiting [the] process of critical, sceptical selection among research priorities ... [that is] presenting buzzwords as substitutes for carefully selected and testable hypotheses about ageing ... might be clever marketing, but it is a poor substitute for scientific thought

Richard Dawkins has considered a related problem: should biologists engage in public debates with creationists on the relative merits of Darwin's theory of evolution versus biblical 'theories' about the origin of species? Dawkins argues that engaging in such jousting contests might be a bad idea, in that such spectacles create, in the arena of public opinion, the misleading impression that biologists consider the 'arguments' of creationists sufficiently meritorious to require public discussion (Dawkins, 2003). Of course, unlike the creationists, de Grey's SENS agenda does not threaten to undermine a central scientific theory or aim to mute opposing theories in schools and in public; however, there are similarities that are worthy of consideration. Treating arguments and proposals that are not backed up by scientific evidence as though they were scientific ideas carries the risk of making them impressive to laypersons, whose main way of distinguishing among hypotheses is to take note of those that are promoted in public media or presented to them by advocates whose style they like. A conference devoted to public transport systems would not be tempted to include a debate on teleportation as an approach to reduce traffic congestion; neither would an editor assembling a special issue on food shortages in the developing world solicit an essay on Aladdin's lamp.

There are good reasons why science tends to award more points for testable ideas than for ill-defined speculations, and more points for results than for ideas alone

Dawkins points out that the scientific community has developed a better way to discriminate among competing ideas: testing them experimentally (Dawkins, 2003). If de Grey believes that he has a good strategy to reverse the ageing process, he should devise a detailed plan for testing his ideas, and then, like the rest of us, convince sponsors that his project deserves funding. If he and his colleagues produce scientific evidence that some aspects of ageing can be reversed by a judicious mixture of phenacyldimethylthiazolium chloride, marker-tagged toxins and IL-7, we promise that we will be impressed.

There are good reasons why science tends to award more points for testable ideas than for ill-defined speculations, and more points for results than for ideas alone. Science—unlike fantasy—works and leads to discoveries that serve as the foundation for material progress. Creative testable ideas are the lifeblood of scientific progress. In our opinion, however, the items of the SENS programme in which de Grey expresses such blithe confidence are not yet sufficiently well formulated or justified to serve as a useful framework for scientific debate, let alone research. de Grey's credibility, among those who do not know his ideas well enough to understand their weaknesses, lies partly in his claims that his ideas have been judged interesting and provocative by mainstream gerontologists. The authors of this article, proud of our roles as representative mainstream biogerontologists, wish to dissociate ourselves from the cadre of those impressed by de Grey's ideas in their present state.

Modern biogerontology is blessed with exciting new results, new ideas and new hopes for progress, initially in the laboratory and later in the clinic. It is time to draw public attention to these accomplishments and prospects, and to develop public support for this research area as it moves from its stigmatized past to a future in which biogerontological findings could serve as a keystone of preventive medicine. Helping the public discriminate between science and science fiction is an important step towards this objective.

Related article:

Aubrey D.N.J. de Grey's response to this viewpoint appears as a Correspondence in this issue. See page 1000 for 'Like it or not, life-extension research extends beyond biogerontology'.

References

• Dawkins R (2003) A Devil's Chaplain: Reflections on Hope, Lies, Science, and Love. Boston, MA, USA: Houghton Mifflin.
• de Grey AD (2003) The foreseeability of real anti-aging medicine: focusing the debate. Exp Gerontol38: 927–934 [PubMed]
• de Grey AD (2005) Resistance to debate on how to postpone ageing is delaying progress and costing lives. EMBO Rep 6: S49–S53 [PMC free article] [PubMed]
• Miller RA (2002) Extending life: scientific prospects and political obstacles. Milbank Q 80: 155–174[PubMed]