David Bradley – Page 390

X-rays Make Smoother Chocolate

Chocolate

For manufacturers of drugs and chocolate bars, an understanding of how they crystallise can mean the difference between a best-selling product and a flop. X-ray diffraction could help them get a clearer picture at the atomic level.

The taste and feel of chocolate in the mouth depends a lot on the crystal form of the cocoa solids, while some medicines work more effectively in one polymorphic form than another. Until now a crystal clear understanding at the atomic level of how different polymorphs form in everything from chocolate to medicine has been little more than trial and error except in the laboratory setting of the vacuum. Now, Elias Vlieg of the Department of Solid State Chemistry, at the University of Nijmegen, describes how X-ray diffraction (XRD) techniques can be used to study crystals as they form and so provide clues as to how their growth can be better controlled. The chance of tastier chocolate and more efficacious drugs is on the horizon.

If the growth of crystals were clear-cut, there would be no need to study crystal growth, but many compounds can crystallise in different – polymorphic – forms. Even a material as seemingly simple as carbon has several polymorphs – graphite, diamond and fullerite. The differences between polymorphs of the same compound can be tiny, an atom shifted slightly to the left, or a tighter angle between two bonds. But, they can also be quite large differences that impact on the overall properties of the solid. For a drug in solid form this can have a real impact on how well it is absorbed by the body. One polymorph may take longer to be dissolved and absorbed while another might be faster acting. The result can also alter the drug’s side-effects. A slowly absorbed drug might sit in the stomach too long and cause irritation of the lining of the stomach for instance.

On the lighter side, the minute crystals of cocoa solids in a chocolate bar affect how the bar melts in the mouth. One crystal form may have a more pleasing texture on the tongue than another. According to Vlieg, XRD has been wholly successful in observing crystal growth in a vacuum. But for crystal growth from the more industrially realistic setting of a solution, melt or solid, it has until recently been little more than a dream tool.

Now, XRD is beginning to offer information on the structure of both sides of a growing interface. This, explains Vlieg, means that structural details like relaxation and reconstruction on the crystal surface and ordering in the solution can be included in the theoretical description of crystal growth.

Understanding crystal growth in vacuum and beyond, Surface Science, in press.

September 11

I am actually writing this article in the future…it’s the 11th of September 2023.

In 1988, I spent a summer working in the US. It was the time of my life at the time. I’d just graduated university and flew into JFK not a week later, spent just one night in NYC but took photos of the “twin towers” etc from the top of the Empire State Building. I fell in love with New York. Several months later I’d be staying in the same YMCA again and then flying home via JFK to a miserable London and then back to Newcastle. On that final night in NYC, window open, there were sirens and gunshots, outside it was American…my flight home was just days away from the Lockerbie disaster…

When the 9/11 attacks were underway, I was working on a deadline for one of the very early online science news sites I helped establish back in the late 90s. I had disabled my internet (modem) and had been focused on nothing but the research I was writing about. I hadn’t had a moment to leave my office to switch on the TV to catch the news. In fact, it got to 3:15 in the afternoon before I knew anything was happening in NYC and elsewhere. Mrs Sciencebase too had been working on something else and was also unaware until we reconvened in the living room to switch on BBC News 24, as it was called then. It was a shock to say the least. Unreality bit.

There has been, as the cliche goes, much water under the bridge since then.

Water, water

This article originally appeared in my Catalyst column in the original incarnation of ChemWeb.com back in the year 2000, it seems like ancient history now. However, the PI got in touch recently and was asking if there were an archived version of the article online. Sadly, there wasn’t other than his own site’s copy, so here’s my original for the record.

I always fancied the idea of polywater and what it might be able to do. But, then I also quite like the idea of using chemistry to convert lead into gold, a money tree and the magic porridge pot. While, polywater may have turned out to be a lost cause, chemists have for many years unearthed some quite bizarre properties from the liquid of life, writes David Bradley.

The discoveries about this elemental material continue to this day with a collaborative team from Japan and the US publishing results in Nature recently (30 November 2000) that show that water becomes a two-dimensional glass and shrinks under extreme pressure when cooled and confined.

To the ancients, water must have seemed such a simple yet marvellous material – primordial, straightforward, life-giving, ubiquitous and, to them, elemental. Indeed, until we began looking more closely at its physical properties and the underlying physical chemistry, the hydrogen bonds, polarity and such it remained that way.

Water is indeed a simple-seeming substance – a couple of hydrogen atoms stuck on an oxygen making a boomerang shape. Couldn’t really have been any more uncomplicated, really, straight perhaps? But, water is not, as any high school science student would hopefully be able to tell you. Up to a point it expands when it is cooled below 4 Celsius. It expands just enough to make the perfect Scotch on the rocks and to have left the Titanic in the same predicament.

Water is also rather unusual in that unlike most other materials it exists in all three standard states of matter – solid, liquid and gas – at temperatures that are not at all outside our everyday experience. The likes of carbon dioxide, common salt and egg white, just don’t have that ability to flip between states within a 100 degree range. Add to that the fact that it is far more viscous than other similarly sized molecules, it can readily be converted into that increasingly familiar supercritical fluid state for which chemists are finding green applications at every turn. The list goes on – unexpectedly high heat capacity, solubilising capacity, hydrating ability?

Microstructure of water

Much of water’s anomalous behaviour boils down to the formation of hydrogen bonds between those dangling hydrogens on the boomerang tips and the oxygens on neighbouring molecules and the tiny clusters of water molecules that exist fleetingly in the liquid state but lost in the gas and frozen in the solid.

In 1992, I reported on work from Sydney Benson and Eleanor Siebert of the University of Southern California at Los Angeles for New Scientist (see New Scientist archives). They used experimental data for ice and for pairs of water molecules in the gas phase to construct a theoretical model of liquid water. They claimed that the microstructure of water could help explain many of water’s unusual properties. Their model help them envisage transient cubes of water molecules held together briefly in groups of three or more – with their hydrogen bonds breaking and reforming some 500 billion times a second.

Where are the clues?

Later work provided further solid theoretical clues about water’s hidden properties. David Clary and John Gregory of the chemistry department at University College London used quantum Monte Carlo methods to simulate millions of possible random configurations of water molecules and came up with a hexamer that would be plausible under Schroedinger’s equation. While such theorising may ultimately lead to a way to predict the properties of water from first principles, since it is this molecular behaviour that gives rise to the bulk effects, water still holds plenty of surprises for those scientists who keenly take to it.

Xiao Cheng Zeng, Associate Professor of Chemistry at the University of Nebraska, Lincoln, working with Kenichiro Koga of Fukuoka University of Education and Hideki Tanaka of Okayama University in Japan have found that they can make water form a glass rather than ice crystals at -10 Celsius by confining it in a tiny slit just 1 nm across.

Three years ago, Zeng and Koga who was at the time a postdoctoral fellow at UNL, and `ice expert Tanaka’ were using computer modelling to look at the way water changes when it is put under extremes of pressure. The model showed that rather than expanding on freezing water it can contract if it is squeezed at 493 atmospheres at -40 Celsius between two hydrophobic plates held a nanometre apart. The model showed that water was freezing into ice crystals with a hexagonal structure where every water molecule is hydrogen bonded to its four nearest neighbours but rather than being in a three-dimensional lattice the crystals were planar. Zeng confesses that he figured Koga’s model was simply incorrect, they were looking for water glass, or ice glass, and had stumbled across a new two-dimensional crystalline form instead. “We ran many, many trials for about six months,” Zeng says, “but we found the water froze into crystals and shrank every time.”

Koga, Zeng and Tanaka were actually hoping to find a mixture of pentagons, hexagons and heptagons in the molecular structures of the water and thought it would be fairly easy to reproduce in the laboratory. But, it has taken three more years to come up with the real thing.

Frustration was the answer

The trick that finally did it was to introduce `frustration’ into the process. This simply involved holding the two hydrophobic plates immobile while the water was compressed and frozen. The effect was to totally inhibit the formation of a true crystal and force the water to form a glass instead. It worked.

Zeng says he has nicknamed the new form of ice `Nebraska’ ice from the Otoe word for `flat water’. But, aside from an interesting addition to the list of water’s bizarre behaviour is there likely to be any immediate applications? Zeng does not think so, his reward, he says, is the simple joy of discovery. “Water is such a fundamental substance that it deserves a lot of attention and we want to understand it from every aspect, from its nanoscale behaviour, from its molecular properties, and all the way up,” he explains.

Maybe what we have learned so far about water is just the tip of the iceberg. Now, pass me that Scotch, with a touch of water, of course.

Carpet Consumers

Trust a scientist to take consumer rights to the extreme. Analytical chemist Gerry Clark bought a new carpet for his son’s bedroom. The carpet had that common ‘new carpet’ smell but after several weeks it still hadn’t dissipated and Clark began to worry about the fumes to which his child was being exposed.

He took a chunk of the carpet into his lab and recorded a gas chromatograph (GC) for the volatile emissions. Sure enough, there were spikes due to several organic compounds. Clark took the test sample back to the shop together with his GC results, complained, and insisted the sample be sent to the manufacturer.

A week later, the company was in touch offering a replacement because the original carpet had obviously not been left to dry long enough before dispatch to the outlet. Needless to say everything smells rosy now.

Such tales are all very well for lab chemists, but what about the rest of us fobbed off with fusty floor coverings, smelly sofas, and pungent pouffes? Maybe consumers should set up an action group with its own labs to help people make a scientific case for complaints. It could be called the Prevention of Odourous New Gear Society. Or STENCH, STINK, REEK…or whatever.

Elemental Discoveries – April 2000: Exploding cubes

US chemists have synthesized a new type of explosive that could be more powerful than the most potent non-nuclear compound known.
The compound was synthesized by Philip Eaton and Mao-Xi Zhang at the University of Chicago by building on the building block hydrocarbon cubane. Cubane, first synthesized by Eaton and Thomas Cole, in 1964, is one of the most dense hydrocarbons ever made and has always been known as a highly strained compound that stores a great deal of energy,’ explains Eaton.
Eaton and Zhang have developed a methodology involving non-standard procedures at each step to swap cubane’s corner hydrogen atoms with nitro groups – ultimately producing octanitrocubane. Nitro groups are common constituents of explosives for example in trinitrotoluene (TNT). The nitro groups provide oxygen for combustion of the carbon to carbon dioxide and release of nitrogen gas – explosively.

Eaton says the compound is shock insensitive so he can safely hit it and its hepta precursor with a hammer. However, deliberately detonating it is highly explosive. Calculations show that the detonation velocities and pressures will be far greater than those of TNT and more explosive than HMX (high-melting explosive. Eaton says octanitrocubane may prove to be the most powerful non-nuclear explosive around.
Octanitrocubane might have applications in mining and demolition and in propellant applications. Angew Chem Int Ed Engl, 2000, 39, 401

Throwing out the silicon

‘Silicon chips with everything’ was one of the great puns of the 1970s and for more than thirty years the tiny etched elemental slivers have spread like a rash over every facet of our lives – find their place in running phones, TVs, washing machines, medical equipment, cars, and of course computers.
Getting more power out a silicon chip means cramming in smaller and smaller logic units into the same space. But there is a limit dictated both by the shortest wavelength X-rays we could use to ‘print’ the features and the quantum uncertainty that may arise as these features are packed closer and closer together. Nature, of course, may have provided scientists with a model answer.
Nucleic acids RNA and DNA – the carriers of one of the neatest digital information systems we know – might in the coming decades begin to displace the computers of doped silicon and its inorganic cousins for certain computational problems and replace it with chips based on the stuff of life. Leonard Adleman at the University of Southern California was the first scientist to begin using nucleic acids to solve mathematical puzzles. In 1994, he solved a version of the ‘traveling salesman’ problem. He used the DNA bases to represent combinations of stretches of the salesman’s journey and an enzyme that could recognize and cleave those that did not correspond to an optimum journey to compute the most efficient route. Molecular biology tools – enzymes, nucleic acids and such, were thus used to demonstrate the feasibility of carrying out computations at the molecular level.
Two papers published in Nature and the Proceedings of the National Academy of Sciences demonstrate the proof of principle that shows just how plausible a nucleic acid computer might ultimately be.

Evolutionary biologist Laura Landweber collaborated with computer scientist Richard Lipton, Dirk Faulhammer and Anthony Cukras to see whether they could solve a basic chess problem. The so-called ‘knight problem’ asks how many and where can one place knights on a chessboard so they cannot attack each other. Such a problem is known mathematically as an example of an ‘NP-complete’, which means the possible answers increase exponentially with increasing variables – in this case squares on the chessboard. The knight problem represents a class of mathematical problems that can best be solved by simple brute-force computation rather than a complex logical approach. So, to number crunch the problem, the team built a computational system from 1024 different strands of ribonucleic acid (RNA) combinations to look into this problem. Each strand of RNA represents a configuration of pairs of knights and to simplify the demonstration the system is equivalent to a nine-square chess board (3 x 3) so that there are a ‘mere’ 512 possible combinations of knights rather than the millions possible with a standard 64-square board.
The team used a targeted ribonuclease enzyme which seeks out specific combinations of bases along the strands of RNA and cleaves those that are marked by base-pairing to short DNA probes. By choosing to mark exactly the right bases the enzyme will cleave only those strands of RNA representing an incorrect combination – the wrong solutions to the knight problem, explains Landweber. All the team then needed to do was to analyze the remaining ‘whole’ RNA strands to find the answers to the problem.

Landweber and her colleagues correctly identified 43 solutions to the knight problem with their RNA computer. It’s a start but is it a total solution? Landweber explains: ‘Each molecule represents a solution. We do not need to recover all of the actual solutions, since that would just be tedious, and that is not the challenge. By sampling, if we collected a large enough set we would probably get them all, keeping in mind that some would come up more than once just by the probability distribution.’ The team also points out that their system also kicked up one incorrect solution, which re-emphasizes the need for error checking within any computer system.

The main advantage, of course, adds Landweber, is that nucleic acids can have a much higher information density than any silicon chip – a gram of dried DNA could hold as much information as a trillion CD-ROMs, it is thought.
Meanwhile, a team at the University of Wisconsin-Madison has demonstrated that it might be possible to incorporate DNA itself into more solid devices that might ultimately be interconnected to electronic components. The free-floating world of solutions has always been a barrier to the acceptance of molecular computing. The main question is always how would a chemical solution be connected to real-world input and output devices such as keyboards and monitors?

Chemist Lloyd Smith and his colleagues have now shown they can attach a potentially computing set of DNA strands by one end to a gold-coated glass surface. They use their DNA-device to eliminate incorrect solutions from another NP-complete problem known as the satisfiability problem, which is essentially the knight problem phrased differently. By exposing the tethered strands to free-floating strands carrying sequences complementary to those satisfying each criterion met by the correct solution they could produce double helices. The incorrect solutions at each step are then exposed to a cleaving enzyme. Gentle heating regenerates single strands and the next DNA complement is added as the next criterion and so on. Decoding the single remaining double strands provides the problems solution.

Smith concedes that nucleic acid computing is still a long way from approaching silicon technology. This is simply a test-bed for working out an improved and simpler chemistry for DNA computing, he says. Test-bed or not with the possibility of an information density a million million times higher than a CD-ROM there is an enormous incentive to get to grips with the shrinking world of computers.

L. M. Adleman et al., Science, 1994, 266, 5187.
L. Landweber et al., Proc. Natl. Acad. Sci. (USA), 2000, 97, 1385.
L.M. Smith et al., Nature, 2000, 403, 175.

Sperm tap

Richard Evans, Catrin Pritchard and their colleagues at GlaxoWellcome discovered a way of blocking the path of sperm from the testes, which could produce semen that is virtually sperm free without the need for an irreversible vasectomy.

On the other hand, as it were, the control they have discovered could also be used to enhance the movement of sperm from the testes and so may have potential in male fertility treatment too.

I often wonder with these fertility researcher people whether they do their research manually…maybe not. For more on male fertility research check out the sperm tap article over on Reactive Reports.

Interview with Rupert Sheldrake

Rupert Sheldrake – Born: Newark-on-Trent, Notts, United Kingdom, June 28, 1942

Position: Fellow of the Sausalito, California Institute of Noetic Sciences, an independent research center studying consciousness and the nature of the mind.

Biography: Ph.D. in biochemistry as a Clare College research fellow. 1967-1973, director of studies in biochemistry and cell biology. 1970-1973, Royal Society fellow at Cambridge. 1974-1978, principal plant physiologist at the International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) in Hyderabad, India, and a consultant there until 1985. Frank Knox fellow, Harvard University fellow. Married to Jill Purce, with two sons; lives in London.

Sheldrake is quite well known in the United Kingdom as a maverick biologist because of his outspoken views on the nature of reality and, in particular, phenomena that are not usually considered “real” by science, such as the behavior of animals before an earthquake. His theory of morphic resonance, which he describes as “the basis of memory in nature,” might, he says, explain everything from the shapes of growing trees and phantom limbs to how homing pigeons home, as well as the animal-earthquake connection. But the theory has been the object of much scorn and derision from traditional scientific quarters because of its holistic and nondogmatic approach to nature. Sheldrake empathizes more, perhaps, with Alfred Russel Wallace than with Wallace’s more famous contemporary, Darwin. He believes that biology has lost sight of its holistic roots in its eagerness to provide a reductionist explanation of life.

Sheldrake’s latest book, Dogs That Know When Their Owners Are Coming Home: And Other Unexplained Powers of Animals (Crown, October 1999), seeks to explain animal and human behavioral phenomena that are considered to be outside the domain of conventional science. For instance, many people who have ever owned a pet will swear that their dog or cat or other animal has exhibited some kind of behavior that they just cannot explain. How does a dog know when its owner is returning home at an unexpected time? Sheldrake claims that his intensive research over the last five years demonstrates a strong connection between humans and animals that lies beyond present-day scientific understanding.

How would you describe yourself?

A biologist interested in exploring areas that lie beyond the boundaries of usual research.

What first inspired you to go into your field?

A love of animals and plants when I was a child, and a father who was an amateur naturalist who encouraged and nurtured my interest.

What do you enjoy about your work?

I can work freely and follow up any leads I find interesting because I work independently. I have been exploring unexplained areas of animal and human behavior, such as the feeling of being stared at from behind, which most people brush aside. I have done over 20,000 simple trials that suggest this is indeed a very real phenomenon.

Why do you think we have this “sense”?

I think it could have a major evolutionary role to play. For instance, if a prey animal can tell when a hidden predator is looking at it without being able to see, smell or hear it, then this would have survival value. Its presence in modern human beings may well be a relic of this.

So, what’s the explanation?

Conventional science cannot explain the effect, so it has been largely ignored. My own feeling is that morphic fields are involved.

What do you dislike about your research field?

There’s nothing wrong with the field of research as such, but most scientists don’t take it seriously, and there is no whole community working on these questions, so one sometimes feels isolated. Most of the time, that’s an advantage, because it’s much more exciting to explore uncharted territory rather than simply fill in the gaps in a heavily populated area of science. But I do miss some of the excitement of having a lot of bright colleagues engaged in similar research.

What aspects of science would you change if you could?

What upsets me most about science is the closed-minded dogmatism that is all too common, which makes a lot of scientists timid and afraid to go beyond convention. This affects cosmologists and physicists a lot less than biologists. After all, you can still be a cosmologist and speculate that the universe is one of an infinite number, or postulate extra dimensions of space and time. At one time, these were considered the realm of cranks, but now you can hold down a chair in a physics department. In biology, the atmosphere has become narrower and more intolerant as molecular biology and neo-Darwinism have squeezed out the traditional, holistic approach. Biology has become rather narrow and impoverished.

When did things change?

The craze for molecular biology and the success and excitement in that field have done a lot to draw attention away from whole organisms in favor of a more reductionist approach. This began in the 1920s, and the discovery of DNA carried the process further.

What was your first scientific experiment?

I must have been about seven or eight. I was fascinated by homing pigeons. I kept some, and my first experiment was to take one of them away and release it and find indeed that it came back.

How did the experience increase your maturity as a scientist?

I had no theory of my own at the age of seven or eight. But it showed me that pigeons seem to have knowledge of where they are in the world. All the scientific explanations put forward so far have been refuted experimentally, even the notion that a built-in “compass” may be the answer – knowing which way is north, after all, says nothing about where home is. It’s a problem that has stayed with me all my life, and I have never felt satisfied when people say it is just a matter of genes, proteins, or synapses.

What was your high-school science teacher like?

My biology teacher, Robin Thoday, was very inspiring. His father was a botany professor and his brother a geneticist, and he represented the older kind of biology, the traditional biology, where one actually knew the names of plants and animals and studied ecology. His approach encouraged me to look for explanations of things that were unexplained.

Was he a role model?

Not really. He was basically a teacher, and I saw myself in a research role. In a way I saw my father as a role model; he was an amateur microscopist and had his own laboratory at home.

What is your proudest achievement?

There is not a single one, but when I was researching plant development, I discovered that auxin, the plant hormone, is made by dying cells, which sheds tremendous light on the developmental biology of plants. Secondly, in India, working out the basic physiology of the crops I was working on and finding new ways to grow them with high yields. Thirdly, the development of the hypothesis of “formative causation,” which provides a larger framework for looking at nature.

What was your most embarrassing moment?

In India, I invented a new cropping system for growing pigeon peas as a perennial, and persuaded village farmers to take this up. It was a terrible failure because the peas were killed by disease that persisted on the perennial crop, which wouldn’t have happened if the crop had been grown in the traditional way. I did arrange for the institute to compensate the farmers, though.

What advice would you give a younger scientist?

If they are interested in making discoveries, then they should explore the unexplained in biology, where no one is working at the moment. I wouldn’t advise them to go into standard molecular biology, protein sequencing, genetic engineering. On the other hand, if they want a conventional career and to earn lots of money, that would be the way to go.

In what areas do you think you need advice yourself?

I work in quite a lot of different areas. In every area, I need advice from people such as statisticians, animal behaviorists, and psychologists, who have worked there longer than I have.

What would you be if not a scientist?

I haven’t a clue. I haven’t thought about being anything else since I was quite young, and I’m delighted I’ve been able to do what I wanted to do.

Who from scientific history would you like to meet?

The evolutionary biologist Alfred Russel Wallace. He’s one of my heroes. He had a much more far-ranging mind than Darwin, and while we know exhaustively about Darwin, we know very much less about Wallace.

What would you ask him?

I’d like to ask him about the biology of Southeast Asia, where he studied extensively. He also had a very different view of evolution than Darwin; he considered there to be creative forces at work rather than just blind chance, and I’d want to know why he thought it was necessary.

Which living scientist do you most admire?

James Lovelock.

Why?

Because of his independence and his ability to think in large-scale terms and not be put off by small-mindedness and petty criticisms.

What has been the greatest scientific discovery this century?

The discovery of the cosmic background microwave radiation, which led to the Big Bang theory. This transformed our fundamental cosmology from that of a static universe, or one slowly running out of steam and gave us instead an evolutionary vision of the whole of nature.

What will be the great discoveries of the next century?

The recognition of the nonlocal effects of the mind is going to transform our notion of consciousness and open up a whole new range of discovery about animal and human nature. This liberation will make science exciting again to lots of ordinary people.

What research goals do scientists need to set themselves?

I think I’d make a register of unexplained phenomena that scientists usually reject, to open up whole new areas of research into, for instance, the restlessness of animals immediately before earthquakes. I think at least 0.1% of science funding should go toward this.

Why do you think the public fears science?

It perceives it as arrogant and, with the GM controversy, it increasingly sees it as a corporate activity with scientists as hired hands rather than following science for its own sake.

What can scientists do to overcome this?

Make it more democratically accountable to the taxpayers, so that a polling system might bring to light the questions that people would really like to see answered. If science addressed interesting questions, it would increase science’s popularity and get children interested again. Research should relate to the problems that arise in our lives. The average person isn’t terribly interested in the genetic sequence of a bacterium or the existence or nonexistence of the Higgs boson, and yet this is where all the money goes in science.

This interview appeared on October 29, 1999, in David Bradley’s monthly BioFeedback column in the now defunct and much missed (not least for the monthly fee!) HMSBeagle on BioMedNet.

Elemental Discoveries – legacy

This is legacy archive for David Bradley’s Elemental Discoveries, which was hosted elsewhere from December 1995 to July 1999. Below is an archive of titles up to June 2006 issue. Here is a more up-to-date listing of the science articles archive.

Archives:

In Issue 93:
June 2006
Coffee and alcohol, The erotic brain, Sperm and eggs

In Issue 92:
May 2006
Llama Caffeine Dip Test, Taxol to a T, Artificial Sweeteners and Cancer, Zoo Poo

In Issue 91:
April 2006
Sex Gets Up Women’s Noses, Carbon Nanosheets, Interview with Martin Walker

In Issue 90:
March 2006
Critical Trials TGN1412, Interview with Steve Bryant, Black Eyed Peas

In Issue 89:
February 2006
Loud music and ecstasy, Uber Pluto, Face Off, Sporty Nanotubes

In Issue 88:
January 2006
Keep Eating Your Greens, Promise of a Rain Garden, Say NO to Straddling Molecules
This is the archive of the original Elemental Discoveries as it operated from Spring 1996 until the beginning of 2006:

In Issue 87:
December 2005
Father Christmas Research – seasonal family trees
Healthy Pregnancy – Pregnant women should exercise more

In Issue 86:
November 2005
Massive black hole – is it or isn’t it?
How to avoid colds and flu – perfectly timed perennial tips
Women in Science – Short review of the story of Dorothea Bate, unearthed

In Issue 85:
October 2005
Bird flu symptoms – why shouldn’t all get in a flap over avian influenza (just yet)

In Issue 84:
September 2005
Scientific Research in the Past – What do museum researchers get up to

In Issue 83:
August 2005
Weights and Measures – Understanding changing fundamental constants

In Issue 82:
June-July 2005
Corporate Academia – science at the commercial end from the people who straddle the divide
Movie physics – science at the movies from the people who put it there
Extreme science – science at the extremities from the people who know

In Issue 81:
May issue of Elemental Discoveries
Automated image sorting – software that does for pictures what OCR does for text
Embargoed news story – revisiting an old issue

In Issue 80:
April 2005 Mechanism of muscle contraction
Adenosine triphosphate, muscle and myosin
h2h TV
Topics in Thermodynamics
Drugs on the internet

In Issue 79:
March 2005 Folding Protein Sensors
X -ray Movies
Material comforts for cyclists.

In earlier issues:
Digging in the dirt – liquid crystals under the illuminating gaze of the Advanced Photon Source
Ibogaine against alcohol and drug addiction – cure-all or hallucinogenic red herring
The latest physics research – into Einstein’s Brownian motion
Spyware, trojans and worms – computer security and viral updates
Envirox fuel catalyst – UK bus fleet equipped with “green” catalyst
Active galactic nuclei – quasars, black holes and galaxies, Royal Society report from David Bradley
Dissecting the atom – Research at ANL’s APS – annual report entry by David Bradley

Catalytic clues – More ANL APS scientific results
SAXS and the water channel – Ditto
Are films ferroelectric? – Yes, according to APS results
Discipline for gold nanocrystals – More good science at the Advanced Photon Source
X-rays shed light on machinery of photosynthesis – another? Yes!
Engineering a solution for gene therapy with plasmid DNA – One more, for now.
Epilepsy research update Guest writer Michael Marshall the epilepsy’s window on the brain
Does the MMR vaccine cause autism? Michael Marshall clarifies the controversy.
More medical news headlines here.
Distribution, that’s the name of the game – Distributed, or Grid, computing
Contractual Obligation – An increasing trend towards the all too casual employment
A hands-on approach to forensic science – The examination of handwritten documents
Deep-sea exploration – How do scientists cope under pressure? In the depths of the ocean?
The growing problem of biopiracy – Attempts to patent and commercialise
Accidents will happen – human reactions to chemicals and biological reagents
Predicting climate change – As carbon dioxide levels double

Science-Based Six Pack

It really irritated me when the USGS created a website called Sciencebase.gov. My site, the original Sciencebase.com, has existed since July 1999. All my social media hangs on that word “sciencebase”, I’ve used it everywhere! It alludes to the foundations of science and information. Anyway, now, when I search on Youtube to quickly find a video of mine, I get some BS marketing about six packs called Science-Based Six Pack. Well, you know what they can go and take a long walk off the same short pier with USGS!

Oh, and yes back in 1999 I probably could’ve even laid claim to having a bit of a six pack myself, hahaha.

This post was written in 2019 and datestamped to the origin year of the one true Sciencebase.

Adverse Drug Reactions

The Wall Street Journal reports (Jan 2, 2009) that a new collaboration between pharmaceuticals giant Pfizer and two Boston hospitals will test whether computerized patient records can boost reporting of adverse drug reactions (ADRs) making it a routine part of filling out electronic patient charts.

Some time ago (Catalyst column, ChemWeb.com, June 1998), I discussed the implications of the more than 100,000 deaths in the US each year allegedly caused by patients’ reactions to their medication – three times the number killed in car accidents. So-called adverse drug reactions (ADRs) are, estimated to be the fourth biggest killer in the US after heart disease, cancer and stroke. Recently, there has been an upsurge of interest in ADRs and calls in the US for an independent body to be established to make control of drugs once they have passed though the regulatory process easier and save lives.

That 100,000 is just a statistic of course, except for those patients and their loved ones affected. Every drug has side-effects and although they do not exist through malicious design, one can perhaps see that the drug R&D process is not perfect.

A pharmaceutical company for reasons of economics and politics cannot possibly study the effects of every putative drug on every ‘type’ of individual in the different circumstances in which it might be used. This is where medication monitoring services come in handy. Pharmacogenomics and personalised medicine that focus on each patient’s single nucleotide polymorphisms (SNPs) may remedy this. But, despite the emergence of inexpensive genomics and predictions of the $1000 genome, this is still true when it comes to administering to the elderly and children as they can be more sensitive than the proverbial adult. Moreover, in the supposedly clinically correct environment of the hospital there are likely to be even more exacerbating factors at work for each individual patient than there might be for a patient with a straightforward bacterial infection, say.

An individual’s genome may be at the root of a particular type of adverse drug reaction. As Catalyst discussed early in 1998. Ten percent of Caucasians and about two percent of Chinese people cannot metabolise the analgesic (painkiller) codeine into its active form, morphine. The drug therefore simply does not ‘work’ for them. The problem boils down to those patients lacking the gene for the liver enzyme CYP2D6 responsible for the conversion. This particular effect was discovered by Alastair Wood a clinical pharmacologist at Vanderbilt University in Nashville, Tennessee. The drug having no apparent effect might lead the GP to prescribe a higher, perhaps intolerable dose. For a Chinese person lacking CYP2D6 the result can be severe nausea.

CYP2D6 metabolises a variety of drugs in addition to codeine, for instance, the antihypertensive propranolol (Inderal), propafenone (Rythmol), for heart arrhythmia, and many of the tricyclic antidepressants. In these cases though people lacking CYP2D6 actually experience an exaggerated effect as the active form stays in their system longer.

In the hospital environment, muscle relaxants used in anaesthesia can be a particular problem for some patients, because they have a faulty gene for the enzyme, butyrylcholinesterase, that would naturally metabolise that drug. For example, succinylcholine stops patients breathing during surgery, this is fine while mechanical ventilation is continued but for some patients the apnoea does not cease and they can die. Peculiar peak concentrations of the TB drug isoniazid have been seen with some patients and have been correlated with a faulty N-acetyltransferase.

In fact, there are many, many variations in drug response that have been recognised and the pharmaceutical companies are becoming well aware of the potential for profit these variations might bring if they can develop drugs tailored to an individual’s genome. The National Institutes of Health in the US has also recognised the potential for improving medicine and is in the process of establishing a Pharmacogenetic Polymorphic Variants Resource database for genes encoding proteins that determine variations in drug responses.

Pharmacogenomics ties in closely with the reporting of adverse drug reactions, although not all ADRs are due to genes. The anti-obesity drugs dexfenfluramine and fenfluramine which are often taken in combination with phentermine – as fen/phen – caused serious ADRs in the form of major heart valve problems in 31% of patients taking the combined medication. The eventual withdrawal of the drug once the problem was widely recognised and publicly known was swift but fenfluramine had been on the market 24 years.

However, while the voluntary reporting of ADRs is fairly common within the medical profession their existence is not well known. Indeed, aside from mentioning a few cursory side effects doctors are often unaware of potentially serious reactions to particular drugs and this is compounded by the fact that all this reporting of ADRs is purely voluntary with the onus on the pharmaceutical companies. As such, there are many people unfairly affected by these drugs and there are actions against pharmaceutical companies like the lawsuit against Levaquin, Actos, etc. It took twelve years before the antihistamine drug used by countless hayfever sufferers every summer was withdrawn in preference to its safer metabolite. The major ADR of terfenadine is potentially fatal heart arrhythmia especially in users taking certain antibiotics at the same time.

A group of medical scientists led by Alastair Wood, published a paper in the New England Journal of Medicine (1998, 339, 1851) calling for an independent drug safety board to be established to keep tabs on ADRs. This body would be there to help protect patients as well as ensuring that medical practitioners were made fully aware of the putative hazards of the countless drugs they prescribe.

According to Wood and his colleagues, ADRs are a serious cause of patient morbidity and mortality. They make the point that there have been independent bodies in place to investigate the likes of plane crashes, train and major traffic incidents, chemical and radiation accidents for many years. These bodies can make recommendations to prevent similar serious episodes happening again following an accident. But, there is no organisation with responsibility for monitoring ADRs and to ensure proposals put forward following an investigation are taken on board.

The ad hoc approach to reporting of ADRs and reactions to drug products seems at odds with the fact that we have Internet and information technology available. Wood and his colleagues say that for all this technology it is remarkable that little use is made of it for drug surveillance to help avoid the huge numbers of deaths that occur. The likes of terfenadine and phen-fen which do end up being withdrawn by the FDA are few and far between and the evidence on which the decision is based while strong is not often in the form of formal statistical analysis. One of the problems is that the US Food and Drug Administration (FDA) does not have the resources to carry this out nor is it in the interests of the pharmaceutical marketers to gather such data.

Wood and his colleagues believe that the solution to the problem is to make this surveillance obligatory through the creation of a body independent of the agency that carries out drug approvals – the FDA. A second, independent body would help avoid conflicts of interest, in that the FDA would not have to investigate problems with drugs it had approved! In their paper in the NEJM the authors state,

We must expect that predicted and unpredicted adverse events from drugs will continue to occur. If we accept that the true safety profile of a new drug is dependent on the experiment that necessarily follows the drug’s release into the marketplace, then we must fund and implement mechanisms to ensure that the experiment is properly monitored, the data appropriately analysed, and the conclusions disseminated rapidly.

Clinical trials can involve a few thousand people, once approved, millions may take it soon after especially now that TV marketing is available in the US to the companies.

Not all ADRs are lethal, just adverse, and some are simply unavoidable because of the individual circumstances in which a drug is administered. They may be unpredictable and unavoidable in some cases but once an ADR occurs the medical community should be made aware of the risks as soon as possible so that better judgements about prescribing a drug can be made and ADRs pushed right down that list of causes of death.

This original version of this article appeared in my Catalyst column in ChemWeb’s The Alchemist in March 1999 before Vioxx, pre TGN1412, and only the intro has been updated January 2009.