Lateral thinking…

[Promoted from my Posterous ‘Overflow‘ blog…]

LATELY I have been wresting with a particular problem in the lab. I have been trying to put a rather complex DNA molecule down on a gold surface with the aim of having it perform the same chemistry on a surface as it does in solution.

Generally, when putting DNA down on a gold surface, we synthesise our DNA with a particular chemical modification, a thiol, on one end of the DNA strand. A thiol is essentially a sulphur atom, usually together with a hydrogen (-SH), and sulphur forms a strong bond with gold, so this is we want.

Unfortunately, we live in a very oxidizing world (basically, everything rusts), so my thiol gets oxidized to a rather less useful S=O. There are numerous other atoms that can reduce my thiol too, such as other thiols, or metals such as magnesium, zinc, copper etc.

This isn’t generally a problem as an oxidized thiol can be reduced back to -SH, making it ready to react with my gold surface.

Only, it turns out that my DNA adheres to the gold at too great a density. Like a mosh pit at a concert, the poor blighters are unable to move, and this results in them being unable to perform the particular reaction that they normally manage when not constrained.

So I modify my approach and use another layer between the gold and the DNA. This layer can be used to dictate how much of the gold surface is actually available to be bound. The chemistry is quite complicated, with several steps, all of which degrade quite rapidly, so it has me running around to make sure I get all the steps completed in time.

First a layer of long floppy carbon chains go down on the gold, and the ends of these molecules are reacted with another chemical that makes them able to react with yet another chemical, this latter chemical being capable of reacting with a thiol. Phew.

I have spent more time than I care to mention trying to get this approach up and running, all the while having to deal with the fiddly, slow and rather cumbersome thiol-based chemistry, which has a propensity to rust.

Then it occurs to me. The only reason I was using a thiol on my DNA in the first place was to stick my DNA directly to a gold surface. As I’ve already determined that we can’t do this (too dense), I really don’t know why I’ve spent time running around testing numerous crosslinking agents that can link the surface to my thiol-DNA.

Time to ditch the thiol and use something that connects DIRECTLY to the first layer of floppy carbon chains.

WHO responds to Sense About Science…

EARLIER this year, Sense About Science, a charity that seeks to promote good science and evidence in public debate, submitted a letter to the World Health Organisation (WHO) asking them to clarify WHO’s position on the inappropriate use of homoeopathy for five serious diseases: HIV, TB, malaria, influenza and infant diarrhoea. The use of homoeopathy as a treatment for such conditions is inappropriate because, basically, it doesn’t work, and the promotion of homoeopathy as a preventative medicine in the developing world is immoral and unethical.

In the letter they cited current examples of homoeopathy being promoted for these diseases, which include:

  • In Kenya, the largest homeopathic supplier, the Abha Light Foundation sells homeopathic medicines for malaria, diarrhoea and influenza. It now runs 20 health centres, 25 mobile clinics and five HIV/AIDS clinics.
  • In Tanzania, Jeremy Sherr and Sigsbert Rwegasira run three homeopathic clinics and claim to have government support to establish a school of homeopathy. Rwegasira claims to treat “no less than 100 malaria patients per day.” According to Sherr’s promotional material, “conventional medicine only supplies temporary relief, often at a great cost financially, and with many severe side effects”.
  • In Ethiopia, the Amma Resonance Healing Foundation, run by Peter Chappell, offers to treat AIDS patients with “resonance healing in the form of homeopathy”, as “an ideal alternative and complement for the treatment of HIV/AIDS in developing countries” because of “the very low costs of producing the remedy” and because it has “no side effects”.
  • In Ghana, the Senya/Tamale Homeopathy Project treats malaria patients with homeopathy.
  • In Botswana, the Maun Homeopathy Project offers homeopathic treatment in several locations and mobile clinics for HIV related complaints such as herpes and diarrhoea “for those people who are HIV+ but who are not taking anti-retroviral drugs”.

Sense About Sense WHO's response

Today the WHO issued a response stating that it DOES NOT recommend the use of homoeopathy for treating HIV, TB, malaria, influenza and infant diarrhoea, with each of the departments tasked with tackling each of these five serious diseases clearly expressing WHO’s position.

Visit Sense About Science to read a briefing document about homoeopathy, so that you can better understand why it is that scientists and medics do not support its use in serious diseases.

Illiberalism in rational causes…

The blogdom of skeptics has been in uproar over the ruling of Mr Justice Eady in the libel case Simon Singh vs British Chiropractic Association (BCA). The case has already been covered extensively, by The Lay Scientist (background | verdict) and Jack-of-Kent (background | verdict).

In Simon Singh’s book, ‘Trick or treatment: alternative medicine on trial’ (review by The Times here), he systematically addresses the pseudoscience of numerous alternative healthcare measures, including Chiropractry, about whom he said:

“The British Chiropractic Association claims that their members can help treat children with colic, sleeping and feeding problems, frequent ear infections, asthma and prolonged crying, even though there is not a jot of evidence. This organisation is the respectable face of the chiropractic profession and yet it happily promotes bogus treatments.”

The ruling hinged on Simon Singh’s use of the word ‘bogus’, which means counterfeit or fake, spurious, or bad. Unfortunately, when you start thinking about it meaning ‘counterfeit’ then this infers some degree of fraudulent use, or deliberate misuse, which is how the judge chose to rule in this case. Mr Justice Eady decided (evidently prior to the hearing had commenced) that the definition would be taken as consciously and deliberately dishonest. In this case it rules in the favour of the BCA where, by the judge’s own reasoning, Simon Singh has libelled them by labelling them deliberately dishonest. It seems strange that a judge can make any objective ruling on the definition of such a word in this case; Mr Justice Eady has effectively ‘cherry-picked’ the evidence by looking at the word ‘bogus’ within a paragraph, without including the evidential support of context from the chapter as a whole.

As I have discovered through word battles myself, different people lean towards different definitions of words when multiple definitions are available. An example might be ‘tautology’, which in one vein can be a rhetorical definition of ‘using different words to say the same thing twice’, yet can also have a meaning in logic of ‘a statement that is necessarily true’. What distinguishes the uses is the context in which they are used, and this seemed to be apparent in this case.

Continue reading “Illiberalism in rational causes…”

Amalgam fillings are safe…

AMALGAM, a compound of mercury with another metal, has been used for fillings for 200 years. A ScienceDaily news article says, ‘Amalgam fillings are safe, but sceptics still claim controversy’.

Speaking at the 87th General Session of the International Association for Dental Research in Miami, Dr Rod Mackert, of the Medical College of Georgia, points out that someone would need 265 – 310 amalgam fillings before even slight symptoms of mercury toxicity could be felt. The reason being that when mercury is mixed with the other metals used in fillings (silver, tin and copper), the compound produced contains no free mercury. A poison is only a poison when it is at the right dose; a fact that has been appreciated for hundreds of years. You may absorb only 1 micrograms (1/1millionth of a gram) of mercury a day from a mouthful of fillings, yet consume around 6 micrograms from food, water and air, according to the US Environmental Protection Agency.

Continue reading “Amalgam fillings are safe…”

Bad Science excerpt: The Doctor Will Sue You Now

bad-scienceBen Goldacre has released the infamous chapter that was missing from the original ‘trade’ paperback edition of his book, ‘Bad Science’. He recently posted the chapter on his Bad Science blog, under a Creative Commons license; this means ‘You are free to copy it, paste it, bake it, reprint it, read it aloud, as long as you don’t change it – including this bit – so that people know that they can find more ideas for free at www.badscience.net

I have reposted the article in full, but you can just as well read it on Ben’s blog, or hell, you could even go spend a few quid and buy his book!

This is an extract from
BAD SCIENCE by Ben Goldacre
Published by Harper Perennial 2009.

The Doctor Will Sue You Now

This chapter did not appear in the original edition of this book, because for fifteen months leading up to September 2008 the vitamin-pill entrepreneur Matthias Rath was suing me personally, and the Guardian, for libel. This strategy brought only mixed success. For all that nutritionists may fantasise in public that any critic is somehow a pawn of big pharma, in private they would do well to remember that, like many my age who work in the public sector, I don’t own a flat. The Guardian generously paid for the lawyers, and in September 2008 Rath dropped his case, which had cost in excess of £500,000 to defend. Rath has paid £220,000 already, and the rest will hopefully follow.

Continue reading “Bad Science excerpt: The Doctor Will Sue You Now”

Letter to The Guardian…

A little long, didn’t fly, but better luck next time.

[Guardian, Tuesday 31st April] Cherill Hicks article, ‘Not to be sneezed at’, gave a timely and largely useful revision of therapies available to hay fever sufferers, but tripped up by suggesting that research on homeopathic treatments was ‘encouraging’.

It is still the consensus in the scientific literature that homeopathy does not perform any better than placebo, an issue which has been addressed by a comprehensive study by Aijing Shang MD and colleagues at the University of Berne, Switzerland. The study, published in The Lancet (2005), compared 110 homeopathy trials with 110 conventional medicine trials, and found that conventional medicines work, with little evidence to say the same of homeopathic medicines.

The positive findings of a few placebo-controlled trials of homeopathic medicines are cherry picked from a mountain of contradictory results, and are generally found to result from combinations of methodological deficiencies and biased reporting. The ‘encouraging’ results for treatment of hay fever with Galphimia glauca arise from a series of studies by a single homeopathy research group, and have been given unwarranted kudos in homeopathy circles due to the publication of a meta-analysis, which is an analytical over-view of combined results from numerous methodologically similar studies.

However, the meta-analysis only consists of seven trials (included in the Lancet study by Dr Shang and colleagues), and all come from the same research group; indeed, the group leader was a co-author on the meta-analysis itself. There are insufficient data from independently reproduced studies to corroborate the positive findings for Galphimia glauca as a treatment for hay fever, thus its status as a recommendable therapy is dubious.

Attention to detail…

[ratings]

Some MOST people would describe me as being a little moderately anally retentive; I have a rather punishing attention to detail, particularly so with the way I approach experiments. Something that really annoys me is when fellow scientists display a degree of slapdashness that borders on being negligent.

Many of us are publicly funded, and one of my aims in life is to communicate science to the public. I love science, both as a system within which I do research, and as a philosophy. If I am to wax lyrical about the rationality and worth of science, and the scientific method, to the public, and use it as a basis in arguments against irrationality, pseudo-science quackery and superstition, then I damned well better practice what I preach. As such I employ the skills and techniques I have learnt in a manner that takes account of these values; I design experiments with good controls, I vary the experimental variable whilst controlling the others. I use evidence-based methodologies that have been tried and tested, thus use minimal materials to achieve my ends in the minimal possible time.

It is not always possible to do this, especially in my current area where there are no protocols for what I’m doing as it’s never been done before. None the less, I form testable hypotheses, design experiments to test them and based upon the result, either modify, scrap or move on.

In your average science lab, based upon the very large number of science labs I have been to, I would have to say that the idea of sitting down and developing a testable hypothesis that makes predictions about outcomes, then designing experiments to test these is probably not what many researchers are doing. What they are doing is ham-fisting their way through protocols given to them by more senior players, which they follow blindly, often without knowing what each step in the protocol is doing at a physical level.

Many of these protocols have been adapted, cut-down and streamlined, which is often another way of describing that short-cuts, often rather slapdash ones, have been introduced. Now there is nothing wrong with this, per se, as long as the protocol is in the hands of a capable person who knows why the protocol has been revised in this way. But, the fact is you cannot instruct a junior member of research staff with protocols that have been cut-down in this way; the full anally-retentive protocol should be provided, or sought, and the researcher allowed to refine it once they’ve identified for themselves the pros and cons of keeping each step.

Continue reading “Attention to detail…”

Premature conclusions

Something the media is very good at, and alas some scientists too, is making a conclusion about a scientific investigation before actually performing the investigation.

This is not how science works!

A recent example of this appeared in today’s Daily Mail, the popular gutter-rag that leads the way in pseudo-scientific sensationalism:

Women who drink coffee or tea during pregnancy may increase their baby’s odds of developing cancer, doctors believe.

Experts say caffeine may damage the DNA of babies in the womb, making them more susceptible to leukaemia, the most common cancer in children.

To establish the link, scientists at Leicester University will scrutinise the caffeine intake of hundreds of pregnant women and compare the results with blood samples from their babies after birth.

Researcher Dr Marcus Cooke said there was a ‘good likelihood’ the study would make a connection. Previous research has shown that caffeine damages DNA, cutting cells’ ability to fight off cancer triggers such as radiation.

Changes of this kind have been seen in the blood cells of children with leukaemia. Scientists know they occur in the womb, but do not know why.

‘Although there’s no evidence at all of a link between caffeine and cancer, we’re putting two and two together and saying: caffeine can induce these changes and it has been shown that these changes are elevated in leukaemia patients,’ added Dr Cooke.

So, they’re planning to investigate this link, though Dr Cooke is quoted as (apparently) saying there is a ‘good likelihood of making the connection‘, despite, as he is later quoted, there being ‘no evidence at all of a link between caffeine and cancer’.

Dr Cooke is also quoted as saying that ‘previous research has shown that caffeine damages DNA, cutting cells’ ability to fight off cancer triggers such as radiation‘; now, I am not going to judge Dr Cooke on the basis of such quotes, because I well know how much gutter-rags like to quote out of context, but I can’t help wondering whether this prior research was a case of caffeine being introduced to cells in a dish, rather than to an actual living and breathing mammal. Any number of chemicals can cause physiological disturbance to cell cultures, but these do not necessarily translate to their being harmful to us generally.

So what’s my problem?

Continue reading “Premature conclusions”

The perils of positivity….

IN science and medical publishing, everything is positive. Less than 4% of articles deal with negative results. There is a perception that negative results are non-results; only positive results are worth publishing. Why is it that showing that something does something is so much more important that showing that something doesn’t do something?

Obviously, I expect some common sense in this; I don’t very well expect that a paper should be published just because you have demonstrated that drinking water doesn’t cause sunburn, this would be a deeply unsurprising discovery. But what if it is a study that demonstrates that a particular drug doesn’t do what people expected it to do? What if it is a biotechnology that doesn’t work for a whole swathe of biological research?

Online science forums (or fora) are replete with anecdotal evidence describing how time, and time, and time again research scientists make the same mistakes, or encounter the same limitations, in particular techniques. This is because no-one ever publishes such limitations, or at least, not more than 4% of the time.

So what is the problem? Well, science is expensive. Very expensive. It is expensive in material cost, and it is expensive in research hours. To have discovered that you’ve wasted a year doing work that elsewhere in the world someone once wasted a similar amount of time doing, only, 3 years ago, is deeply frustrating.

In coffee breaks around the world, many scientists have discussed the idea of a Journal of Negative Results, a compendium that can be consulted at the outset of a research project to determine whether a technique or approach has already been taken toward a research problem, but has been found not to work. Sometimes such negative results a mentioned, but only in passing, and only after an alternative technique resulted in positive results, which resulted in the subsequent publication. They are rarely keyword searchable and thus inordinately difficult to find.

As I mentioned, science costs a lot of money, far more money than is necessary. This is largely because the money isn’t real, there is poor ownership of it, it is monopoly money. If it were coming out of our own pockets, we simply wouldn’t pay the price we do, we’d demand more competitive prices. Consumable companies are free to charge extortionate prices for items that they are producing by the million. I have tubes in my lab that cost £3.75 each; they can only be used once, and invariably one or two of them can be wasted due to one problem or another. Kits are all the rage in research; pre-fabricated methodologies with all the reagents and instructions one needs to perform a particular experiment. The reagents themselves cost practically nothing in most cases, yet the kits can cost anywhere between £300 – £1500, and in many circumstances, afford you between 5 – 20 experiments.

Now this combination of expensive research is part of what leads to negative results being unwanted. There’s no real money in debunking an idea, it must come along side a positive result if it is to come at all. In the pharmaceutical industry, it is part of the reason why any new drug being produced is just too much of an investment to allow to fail, so the pressure is on to ensure, by hook or by crook, that the drug is licensed. Ben Goldacre writes at length about this in his recent book, and blog of the same name, Bad Science; this is most definitely worth a read!

Expensive research also prevents investment into rarer diseases, or any medications that run the risk of having a short shelf-life. One class of drugs that have fallen foul of this economic equation are antibiotics, and this is a rather long pre-amble into what I wanted to say in this blog essay (or blessay, and Stephen Fry attests to horribly calling it).

Continue reading “The perils of positivity….”

Fallacies of logic

[ratings]

THE theory of evolution is an elegant theory, but to really get at the nitty-gritty details takes some discipline and a head for new concepts. There is much excellent literature out there, and plenty online; my links under the title  “Free-thinking”, to the right, are as good a starting point as any.

If you are going to learn about evolution, or science as a whole, then you should hear it from scientists, or other communicators of science, and NOT at websites such as “allaboutscience.org“. With a little reading, you may spot that the site is actually hosted by “allaboutcreation.org“, and I can assure you of three things:

  • There are many such sites on the internet.
  • They use scientific sounding language, but in fact demonstrate complete and universal ignorance of the theory of evolution and of the method of science.
  • They can all be recognised because somewhere they will mention the words “creator” or “designer”; they can’t help themselves. They may also use the word “evolutionist” to describe one who accepts evolution, this is almost uniquely a creationist terminology.
  • Their websites will be based largely around the notion that evolution cannot explain the complexity that is seen in nature, or other notions that they have little comprehension of themselves. Their aim is to raise the more complex issues that they know the average person isn’t going to know about.

They are however flawed because they try to interpret scientific evidence using their own parochial world view, i.e. that we’ve only been here 6,000 years, and we all arrived here in more or less the same form as we are now. Thus they can never hope to understand the time-scales and gradual change through intermediate forms upon which evolution is based.

Here’s an example from the website I cited, on their section about evolution:

Evolution – The Evidence of Why Scientists Believe in Evolution
Evolution, in this context, can be defined as: the belief that all living things, including man, resulted by natural changes from lifeless matter, with no supernatural intervention involved. If life on earth really came to be in this manner, by chance and from lifeless matter, then why are there so many intelligent people — even PhD scientists — who reject the theory?

Well, seeing as this is the first paragraph of the page, one wonders what “context” exactly they’re talking about? Secondly, their definition of evolution is completely wrong; evolution has nothing to say about the origin of life from lifeless matter, this discipline is called Abiogenesis. The theory of evolution, as I’ve described before, explains the origin of species, how natural variation in a species can be acted upon by natural selection over time, resulting in a diversity of different species. By mis-defining evolution, they are attempting to set up a classic fallacy in logic known as a “Straw Man”; by distorting the original definition into something that it clearly doesn’t state, making it easier to defeat, e.g.:

  • Person A has position X.
  • Person B presents position Y (which is a distorted version of X).
  • Person B attacks position Y.
  • Therefore X is false/incorrect/flawed.

Continue reading “Fallacies of logic”