Category: Science

The creation of matter…

[ratings]

NanodropAT SCHOOL we learn that energy cannot be created or destroyed, it can only be converted. As matter is basically energy (revise E=mc2), then it follows that you cannot ‘create’ matter, it can only be converted.

Fortunately for us, we are lucky as a lab, for we have a Nanodrop that is able to achieve the impossible. The Nanodrop is a device used for measuring the concentration of biomolecules such as DNA, RNA and proteins, based upon the degree to which they absorb different wavelengths of light. All labs have such a device, but not all labs have the much lauded Nanodrop.

So when you’ve been labouring in the lab to purify DNA or protein, you then skip down to the Nanodrop in order to determine just how successful your preps have been. However, joy turns to dismay when upon clicking the special ‘Measure’ button on the computer software that powers the Nanodrop, the small value you see tells you that you have very little material; that in fact, you’ve wasted your time.

No longer though, because on our Nanodrop, if you press the magic ‘Measure’ button again, the value increases. In fact, each time you press the ‘Measure’ button, the value continues to grow. Keep doing this enough and you arrive at the kind of value that you were hoping for. With a few mere clicks of a keyboard we can quadruple the amount of DNA or RNA in our sample; an amazing feat given that there is no source of the raw materials needed to create the extra matter.

It really is the most impressive machine in the world ;-p

[update: following this post I was contacted by a representative of Thermo Fisher Scientific (formerly NanoDrop Technologies), to describe why we see the problem. The problem, it seems, is in the Chinese whispers by which one is taught to use the machine. It appears that one is only supposed to take one reading of any sample; repeated measures of the same sample show an an increase in absorbance over time as the 1-2 ul sample, being so small, evaporates – yielding a more concentrated sample. So there you go folks, quite logical really – you still can’t create matter; the search goes on.]


Libel law and scientific disputes…

Re-posted from Jack of Kent, the stated position of the great and the good on the libel case between Simon Singh and the BCA (details of which I wrote about in ‘Illiberalism in rational causes‘):

The law has no place in scientific disputes

We the undersigned believe that it is inappropriate to use the English libel laws to silence critical discussion of medical practice and scientific evidence.

The British Chiropractic Association has sued Simon Singh for libel. The scientific community would have preferred that it had defended its position about chiropractic for various children’s ailments through an open discussion of the peer reviewed medical literature or through debate in the mainstream media.

Singh holds that chiropractic treatments for asthma, ear infections and other infant conditions are not evidence-based. Where medical claims to cure or treat do not appear to be supported by evidence, we should be able to criticise assertions robustly and the public should have access to these views.

English libel law, though, can serve to punish this kind of scrutiny and can severely curtail the right to free speech on a matter of public interest. It is already widely recognised that the law is weighted heavily against writers: among other things, the costs are so high that few defendants can afford to make their case. The ease and success of bringing cases under the English law, including against overseas writers, has led to London being viewed as the “libel capital” of the world.

Freedom to criticise and question in strong terms and without malice is the cornerstone of scientific argument and debate, whether in peer-reviewed journals, on websites or in newspapers, which have a right of reply for complainants. However, the libel laws and cases such as BCA v Singh have a chilling effect, which deters scientists, journalists and science writers from engaging in important disputes about the evidential base supporting products and practices. The libel laws discourage argument and debate and merely encourage the use of the courts to silence critics.

The English law of libel has no place in scientific disputes about evidence; the BCA should discuss the evidence outside of a courtroom. Moreover, the BCA v Singh case shows a wider problem: we urgently need a full review of the way that English libel law affects discussions about scientific and medical evidence.

Signed

Everyone below signed as an individual unless otherwise stated

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Lame theses….

[ratings]

Here is an excerpt of a philosophical lecture series going on at my institution:

The Mangoletsi Lectures 2009: God, Science and Philosophy
Peter van Inwagen, John Cardinal O’Hara Professor of Philosophy, University of Notre Dame

Lecture 4: God and Science II

I return to the topic of a possible scientific disproof of the existence of God. Unlike the discussion in the first lecture, this lecture considers a particular scientific theory in detail—the Darwinian theory of evolution. I give a statement of the theory, present some reasons for being skeptical about whether it is in every respect true, and present an argument for the conclusion that, whether the theory is true or false, its truth is consistent with the thesis that the universe was created by an intelligent being. Finally, I defend a stronger position than the consistency of the Darwinian theory with the existence of an intelligent creator; I defend the thesis that, if the Darwinian theory were true and known to be true, our knowing that it was true would not provide us with any reason to believe that the universe does not have an intelligent creator.

—

He takes a Papal line by stating, ‘I defend the thesis that, if the Darwinian theory were true and known to be true, our knowing that it was true would not provide us with any reason to believe that the universe does not have an intelligent creator‘.

His erroneous use of the phraseology ‘if the theory were true and known to be true‘ demonstrates a fundamental disconnect in this man’s understanding of science. What we can say is ‘the theory is not false, and has been shown (countless times) to not be false’.

What he appears to be saying is, if you can’t disprove the existence of God, then ipso facto, he exists. It is a tenuous, and rather Catholic, position he hopes to defend, that demonstrating the validity of the theory of evolution, as we have, does not give us any reason to believe there isn’t still an intelligent creator. You could just as soon state the opposite. Obviously the existence of God is not open to scientific testing as no testable hypothesis could realistically be formulated; however, we can (and have) amassed enough data to obviate a need for a God in the equation.

Obviously he’s left himself some wriggle room in the form of, ‘its truth [the theory of evolution] is consistent with the thesis that the universe was created by an intelligent being‘; yes, sure, if you want to fudge it into your own creation story go ahead. It could be consistent with whatever you like, feel free to merge the rigorous science with anecdotal and fantastic origins theory, but this does not give it any more meaning, you’re merely hand-waving on the bits for which you have no explanation, i.e. the origins of life (which evolution in itself does not describe).

Meanwhile scientists will continue to remain curious and investigate the actual origins, rather than making up answers.

In preparation…

[ratings]

ON Friday I fly to Melbourne, Australia, to visit my Sister who lives and works out there. I’m not fond of long haul flights, especially when I’m flying economy, but I am very excited none the less. The flight could go either of two ways: I may decide to relax and just watch hours of on demand films and TV, something I rarely get to do on a day to day basis; or I could write. I could write about all the things I’ve been meaning to write about, but haven’t for lack of time.

I wrote a short story in my head the other day about a woman with a huge mole on her nose. She becomes obsessed with it, and the fact that people stare at it all the time ( interestingly the topic of why we stare was covered in a recent article by Wired magazine). After a while the woman decides to have the mole removed, and she is left with a perfect nose, but now no-one stares at her any more. She find this really depressing, she feels alone and isolated, no longer the focus of any attention. Sometimes we surgically excise things from our lives that we think we hate, but in fact they turn out to be crucial to whom we are.

I’ve also been meaning to write about atmospheric microbiology, or aeromicrobiology; it’s a fascinating discipline studying the world in which microbial life surfs the jet stream high up in the atmosphere, surviving the extremely harsh environment: low pressure, freezing cold, low oxygen and high radiation. The Scientist magazine ran an interesting article on it some months ago, entitled ‘They came from above’, by science writer Brendan Borrell (Volume 22 | Issue 12 | Page 36; you can get it via Borrell’s clip archive).

Borrell describes a key event in aeromicrobiology as when Fred Meier of the US Department of Agriculture convinced Charles Lindberg to collect [air] samples during an Arctic flight from Maine to Denmark in 1933, where they found everything from fungal spores to algae and diatoms. Sometimes these wayward, or more appropriately ‘windward’, bugs are more serious that we give them credit. Borrell goes on to describe an outbreak of the [normally tropical] fungal pathogen Cryptococcus near Vancouver in 2001, where vets recorded 12 cases of Cryptococcus in domestic dogs, cats (and even Llamas). The outbreak dated from 1999 and a USDA APHIS report of it is available here, it makes for interesting reading.

The idea that this organism may have arrived on the wind, or may have been lurking in the valley, only for its spores to become airborne and ‘bloom’ in the hot summer of 2001, is understandably something worth investigating. Studies have identified links with atmospheric dust from North African dust storms bringing infectious and irritant fungal spores and allergens to Spain, and even as far as Barbados where one strain (Aspergillus sydowii) was found to be responsible for killing sea fan coral in the Caribbean (more detail about that event here).

Cases of wind-borne fever have been documented previously, in one case people in the populated areas of the Cote du Rhone region of southern France suffered from the zoonotic (i.e. from animal) disease Q-fever, caused by the bacteria Coxiella burnetii, borne the Mistral wind, the cool dry wind that blows through the South of France, from rural areas inhabited by some 70,000 sheep. Obviously there’s not a lot you can do about this, other than monitor such occurrences, but knowing more about it is a good start.

I’m sure there is a backlog of other articles and people I need to discuss, so in the next two weeks you will either see a photoblog of people and places in Victoria, Australia (taken with my new Sigma 10-20 mm lens), or a rather large body of writing. More likely it’ll be a bit of both, or neither; how’s that for clarity?

Anyway, returning to my impending trip, I still have a major experiment to get under way this week, which really does need to go well. I have a lot of man-hours invested in this, and it all essentially comes down to two sets of experiments, each looking for the same reaction to happen in two completely different environments. They’re fiddly, they can easily go wrong, and they’ll be labour intensive – not the best combination when really I should be deciding if I need to decide whether I should be taking sandals or warm boots to Melbourne in Winter.

So it goes.

Evolution of a scientific discipline…

[ratings]

Research bloggingTHE recent issue of Trends in Biochemical Sciences contained an interesting perspective piece from Alexander Shneider, PhD and CEO of CureLab in Massachusetts. He describes a revision, or alternative focus, of Thomas Kuhn’s (1962) theory of scientific (r)evolution. In this Shneider identifies four-stages of evolution through which a scientific disciple must pass to maturity:

Stage 1. The introduction of new objects / phenomena, with an accompanying language to adequately describe such phenomena.

Stage 2. Development of a ‘tool box’ of methods / techniques to probe the objects / phenomena; with advancements in methodologies helping to identify and understand the degree to which other phenomena fall into the realm of this new science.

Stage 3. The stage at which most of the specific knowledge is generated, with the majority of research publications being published, often focussing on the application of new research methods to objects / phenomena. Scientists may re-describe their subject matter using refinements from stage 2, in the same way that with the advent of molecular biology, biologists might re-describe old subject matter from this new context; thus creating new insights, new answers and new questions.

Stage 4. A seeming steady-state for a discipline, where the knowledge gained from earlier stages is is maintained and passed on, often with practical application; often with new means generated to present the information. Whilst ground breaking new discoveries are not necessarily made, this does not preclude crucial revisions to the role of this discipline within scientific environment.

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On the origins of life…

Research bloggingTODAY’S edition of Nature (14 May 2009) features a landmark paper from researchers at the University of Manchester School of Chemistry that describes the synthesis of a pyrimidine ribonucleotide from simple chemicals, which may have existed on an early Earth. The research by Matthew Powner, in the laboratory of John Sutherland, represents a major stepping stone in support of the ‘RNA World’ theory, which describes the origins of life as passing through a stage in which RNA was the sole mediator of inheritance and catalysis, i.e. no DNA or proteins.

You can learn more about RNA World theory at the Exploring Origins website, or via resources on the website of Jack Szostak, one of the pre-eminent leaders in the field who also presents an accompanying perspective in this edition.

Whilst RNA is certainly a versatile molecule, with one form or another capable of breaking itself apart, joining itself to other RNA molecules, promoting formation of peptide linkages (the primary links of proteins) and templating its own self-replication, a major limiting point has existed regarding the origins of the necessary precursors for the RNA itself, i.e. ribonucleotides. Since the late 60’s, chemists studying prebiotic chemistry have focussed on trying to identify conditions in which these ribonucleotides would spontaneously assemble from their constituent parts: a nucleobase (which can be adenine, guanine, cytosine or uracil), a ribose sugar and phosphate. However, this approach was based on the assumption that these sub-units would assemble first, before combining to form the ribonucleotides. Unfortunately, no realistic conditions have been found in which a nucleobase would join to a ribose sugar.

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Nominative nomenclature…

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Those familiar with one end of a biology text book from another will be aware that for the purposes of covenience/brevity/secret codes (take your pick), we use a one-letter and three-letter coding system for amino acids (the building blocks of proteins).

In a paper I must have read several times over the years, entitled ‘The liveliest effusion of wit and humor‘, the author Jan Witkowski describes some of the logic behind the one-letter codes:

The single letter amino acid code was devised in 1966 by an informal group led by Richard Eck, and the derivations of the letters are, for the most part, fairly clear [1]. For amino acids with a unique first letter, that letter is used; for example, I for isoleucine, M for methionine and V for valine. For amino acids with common first letters, that letter is used for the most common amino acid – A is used for alanine rather than aspartic acid, and L for leucine rather than lysine. That leaves a set of amino acids with a more cryptic one-letter notation. F for phenylalanine (Fenyalanine) and R for arginine (Rginine) are fairly obvious but why is W the letter for tryptophan? Eck explains this by stating that ‘tryptophan’ should be pronounced ‘twyptophan’ and, hence, ‘W’ is an appropriate symbol for it. The entry has an asterisk against it, leading the reader to a footnote: ‘My collaborators insist that I take full responsibility for this – R.V.E.’ Unfortunately, this explanation was omitted from later editions and ‘W’ is now supposed to represent the double ring system in tryptophan.

1. R.V. Eck , One- and three letter amino acid abbreviations: mneumonics of the one-letter notation. In: R.V. Eck and M.O. Dayhoff, Editors, Atlas of Protein Sequence and Structure xiii, National Biomedical Research Foundation (1966).

This leaves the infamous five amino acids that most 1st year biochemistry students forget: glutamic acid (E), asparagine (N), aspartic acid (D), glutamine (Q) and lysine (K).

Asparagine, at least, contains an ‘N’; glutamic acid results from the first syllable ‘gluE’; aspartic acid is best pronounced with a US accent, ‘asparDic’ (doesn’t work with an R.P. English accent). I have heard several reasons for why glutamine ended up with Q, and lysine with K (the latter of which is because K is close to L, which was already taken up by Leucine), but none really satisfy. None the less, they’re taught by rote and each generation of biochemists (et al.) is left to find their own reasoning.

Re-awakening ancestral genes…

Research bloggingHUMANS, as we know, are the product of tens of thousands of genes, but hidden elsewhere in your DNA are genes that are no longer functional; these vestigial genes are known as pseudogenes, and they are ancestral remnants from an earlier point in our evolution. In many cases they are simply inactivated duplicates of a current functional gene. In other cases they are genes that have been cut out, reversed and stitched back in; in this position, some believe they may act to regulate the correctly oriented ‘functional’ version of the gene. Alternatively, they may be ancestral genes encoding functions that have become inactive beacuse they are ultimately not necessary for survival. Now, what if we could turn on one of these ancestral genes? One that could actually help protect us from a modern day infection?

In the recent edition of PLoS Biology is an interesting study that describes the re-activation of just such a dormant human pseudogene, retrocyclin, and its potential use as a defensive barrier against infection with HIV-1 (a strain of the Human Immunodeficiency Virus that causes AIDS). Retrocyclin is theta-defensin, which are naturally produced, circular chains of 18 amino acids (a peptide). I have previously research blogged about the application of other such antimicrobial peptides.

Active, functional theta-defensins have only so far been identified in the old world monkeys: the Rhesus Macaque and Olive Baboon; in Humans and other primates, they exist as pseudogenes. At some point in evolutionary history, our ancestors started inheriting a genetic mutation, all be it one that exists at 100%. The Human version of the gene, retrocyclin, is inactive in Humans because of a premature ‘stop’ signal, which makes the cell abandon the production of the peptide too early.

Retrocyclin can be synthesised chemically in a lab, and in this manner that the authors of this paper (from laboratories at the University of Central Florida and UCLA) have previously shown that it is capable of inactivating HIV-1, thereby preventing its entry into cells; in fact, they have also shown that it can similarly prevent entry of Herpes Simplex Virus type I (responsible for coldsores) and type II (responsible for genital warts).

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