Category: Biology

Mutant Venus Flytraps Catch TNT

Computation could allow new high-affinity and specific protein receptors and sensors to be designed for any number of small molecules of interest, thanks to researchers in the US. Such artificial receptors could ultimately find a role to play in medical diagnostics, drug design, and sensors.
According to biochemist Homme Hellinga and colleagues at the Duke University Medical Center, Durham, North Carolina, the formation of complexes between proteins and ligands is a fundamental interaction in molecular biology that lies at the heart of countless biological process.

Hellinga points out that manipulating the molecular recognition between ligands and their associated proteins is crucial to basic biological studies. From a technological standpoint though, improved understanding could also allow us to create bespoke enzymes, tailor-made biosensors, genetic circuits, and to carry out chiral separations very effectively. With such rewards in the offing it is not surprising that the systematic manipulation of binding sites is still “a major challenge”, Hellinga emphasises.

The team has taken a novel approach to improving our understanding of protein-ligand interactions. They have devised a structure-based computational method that can be used to redesign protein ligand-binding specificities, which can then be engineered into a microbial genome for fermentation-like protein manufacture. In a commentary on Hellinga’s research, William DeGrado of the University of Pennsylvania School of Medicine, Philadelphia, explains how organisms use many different small molecules that bind to proteins. Receptors, enzymes, and antibodies for instance all interact with small molecules to control cell communication, signalling, and protection against pathogens. Exploitation of these interactions has so far been limited, but diagnostics and new disease therapies could emerge from greater understanding of them.

The researchers have demonstrated how the approach works by constructing new soluble receptors for the explosive TNT (trinitrotoluene), the sugar L-lactate and the medically important hormone serotonin (5-HT). The new receptors have high selectivity and affinity for their ligands and could be used as the sensing component of a detector. Intriguingly, the team has also incorporated their new proteins into a synthetic bacterial signal transduction pathway, which means they can be used to regulate the switching on and off of various genes in response to the presence of TNT or L-lactate in a bacterial culture. “The aim is to create synthetic signal transduction pathways that may allow bacteria to function as biological sentinels to chemical threats and pollutants in the environment by switching on a reporter gene,” Hellinga told us.

They started with a series of bacterial periplasmic binding proteins (PBPs) from Escherichia coli, which DeGrado describes as “Venus-flytrap-like receptors”. These PBPs are composed of two protein domains that snap shut on their ligand, just as the fly-catching plant’s specialist leaves grab their prey. When the ligand binds, a signal is transmitted. “In vivo the signal is binding of the closed form of the protein to a transmembrane receptor that triggers a cytoplasmic phosphorylation cascade that ultimately results in transcriptional activation of a reporter gene,” explains Hellinga. The natural function is the control of chemotaxis or outer membrane protein expression, depending on the system, and the natural ligands include sugars and amino acids. The researchers wanted to redesign the PBP’s trap so that it would bind a range of other small molecules in order to engineer “biological sentinels”. They chose L-lactate, serotonin (5-HT), and TNT as their targets as these compounds demonstrate great molecular diversity structurally and chemically diverse, both from one another and the natural PBP ligands.

A computer model of the PBPs was then investigated by placing a “virtual” version of TNT, 5-HT or lactate in the trap. Their powerful algorithms then mutated the binding site amino acids one at a time and scanned for new protein sequences that had a surface into which the ligand would fit. The results are astounding, with just 12 to 18 amino acids being changed, 10^23 possible sequences are generated, many more than achievable with conventional methods. Moreover, if ligand approach is also considered the combinatorial possibilities rocket to between 10^53 and 10^76.
To screen such a vast array of virtual proteins, Hellinga’s team then used another algorithm – an enhanced version of “dead-end elimination”. The original algorithm was developed by Frank DeSmet of the Catholic University of Leuven, Belgium, but was then enhanced substantially by Hellinga’s team. Further work then allowed them to handle the design of ligand-binding sites needed for their research. The algorithm queries an entry in the library on the basis of hydrogen bonds, van der Waals interactions, electrostatic interactions and atomic solvation. However, rather than scanning each individual entry those library members lower down the diversity tree are pruned off if they don’t fit. The rationale for this being that if a lower member does not fit, then any twiglets further along its branch won’t either. In this way, only the mutant Venus fly traps with a global energy minimum are retained for further investigation. The result – from billions and billions of possibilities, the researchers have pruned down to a top seventeen.

The researchers synthesised these seventeen potential receptors and tested them in vitro against their target small molecules. Fluorescence measurements shed great light on each, revealing them to be highly specific and selective for their respective ligands.

Until now, explains De Grado, the proteins in question have been “developed” either through the generation of large libraries of proteins for testing and improved through evolutionary type methods. However, this is time wasteful and energy consuming. As De Grado points out the Hellinga team has now accomplished the task of creating such a library and screening it by a very rapid computational means.

References

Nature 2003, 423, 185; Loren L. Looger, Mary A. Dwyer, James J. Smith & Homme W. Hellinga
Nature 2003, 423, 132; William F DeGrado.

A Wild Recipe for Hot Soil

Chernobyl accident

The French have always had a penchant for fungi, but one day you may be more likely to find a cep cleaning up after a terrorist bomb or a nuclear accident than being served up in a wild mushroom soufflé.

Edible mushrooms might not be the most obvious choice for cleaning up after a nuclear accident or the explosion of a so-called “dirty” bomb, a conventional explosive carrying radioactive material. But, French scientists reckon that a wild mushroom might soak up radioactive caesium-137 ions just as easily as it can olive oil. Caesium-137 was released in vast quantities by the explosion at the Chernobyl nuclear power station eleven years ago and could be a major contaminant from a terrorist dirty bomb.

Removing metal and radioactive contaminants from exposed land is a crucial task. Aside from the immediate threat to the environment and the health of those living on or near such land, toxic metal ions can be carried into the food chain by vegetation growing on the land. One clean-up solution, known as bioremediation, involves deliberately planting plant species that might absorb the metals from the soil and then harvesting plants for safe disposal.

When it comes to the alkali metal caesium, however, there are no plant species that thrive on soil contaminated with it. So, if not a plant, why not a fungus?

Anne-Marie Albrecht-Gary and her colleagues at the Louis Pasteur University and the University of Strasbourg think they have found the solution in the unlikely form of the tasty bay boletus, Xerocomus badius. “Fungi often exhibit a remarkable ability to accumulate a large variety of elements, ranging from the heaviest of the transition metals such as lead or mercury, to the alkali metals, including radioisotopes like caesium-137,” explains Albrecht-Gary in a recent issue of Chemical Communications. But, she adds, little is known about how these fungi take up such metal ions.

She and her colleagues have studied the chemistry of the two pigments that give the inside of the bay boletus cap its bright yellow colour – norbadione A and badione A. These chemicals can act like molecular crab claws grabbing hold of metal ions in a pincer movement known as chelation. The yellow colour of the pigments provided the team with the means to test how well each latches on to metals, such as caesium. They exploited the pigments’ strong absorbtion of ultraviolet wavelengths to record a spectrum of the free pigment molecules and their spectra in the presence of caesium ions are markedly different. UV spectroscopy coupled with chemical analysis revealed that norbadione A in particular can bind to radioactive caesium very strongly. In fact, so strong is the norbadione claw that it can bind two caesium ions, whereas its weaker sibling badione A only has the strength to grip one at a time.

Albrecht-Gary and her colleagues believe that norbadione gets its strength from a so-called allosteric effect. When one caesium ion enters the claw, the molecule’s chemistry changes slightly so that a second gripping position opens up to accept another caesium, working like a double claw. Badione A, on the other hand has only one possible grip.

The researchers believe that norbadione A makes the bay boletus so good at sequestering radioactive caesium ions from the soil in which it grows that it should be the bioremedial agent of choice for removing this hazardous metal from contaminated land. “Obviously, fungi can be very efficient at accumulating toxic metals and radioelements and constitute an excellent and elegant tool for soil bioremediation,” says Albrecht-Gary, “However, the limitation on this very potent application is controlled growing of the mushrooms.”

Mushroom

While norbadione A will almost certainly have a role in bioremediation, the team has dashed hopes for its medical use in removing toxic metals, such as radioactive caesium-137 cadmium and nickel, from the body. Its grip on other alkali metals, such as the essential minerals sodium and potassium is just too strong.

Of, course one problem remains: what to do with the radioactive fungi…one can hardly cook them in an omelet.

Sensing a turn on

The list of biological processes that rely on nitric oxide (NO) continues to grow – it is involved in muscle relaxation, the immune response, memory and, of course, sexual arousal and plenty more besides. Ever since that discovery, if not before, I suppose you could say that saying NO has become a prerequisite for sex. Although for legal reasons we should disassociate ourselves from such a puerile, or should that be penile, comment. For more chemical fun and games, check out Paul May’s silly molecules page at Bristol University where you will find arsoles, cummingtonite, and spermine. Over on ChemSpider.com you will find similarly puerile behaviour in the form of coxafloppin, mycoxadroopin, and more.

Talk about the birds and the bees

Can anyone explain why we use the phrase “the birds and the bees” as a euphemism for explaining the facts of life to our children? Surely the sex life of bees is about as different from most people’s as you can imagine and birds…well…unless you’re talking about the male ostrich and a handful of other birds they don’t even have anything vaguely like the same “bits”.

I’ve often wondered why the honey and feathers didn’t go down too well on our honeymoon night.

Sex toy

A while ago now, the state of Alabama, USA, passed a noble law making it illegal to sell any device ‘for sexual stimulation of the human genital organs’. In other words if you fancy self-gratification with an appliance of science you’re stuck. The State argued that good vibrations in the bedroom are obscene.
Subsequently, however, six frustrated women went to court in an attempt to get the law overturned on the basis that it violates privacy rights.

The offence carried a $10,000 fine and a jail sentence. But, I wonder, in a country where free expression is so proudly proclaimed, and at a time when serious ethical and moral dilemmas are high on everyone else’s agenda, did Alabama waste taxpayers’ money arguing the toss over dildos?

Clams on Prozac

The sex connection with oysters (I don’t mean sex with them, obviously, but that they’re supposed to be an aphrodisiac) is obvious but what about clams on Prozac?

A US biologist claimed to have discovered that the anti-depressant can help improve the sex lives of shellfish. According to Peter Fong of Gettysberg College he found that the drug stimulates freshwater fingernail clams and zebra mussels to spawn, which could be useful for clam and mussel farmers. A clue as to why lies in the effects of Prozac on raising serotonin levels – the compound not only affects human mental happiness but is the trigger for spawning in these creatures.

Fong added mysteriously that rarely has either animal been observed to spawn in the wild or in the laboratory without the use of an artificial chemical aid. I was puzzled then as to how these aquatic creatures managed to reproduce successfully for millions of years before the invention of Prozac.

Stick with grubby bedsheets

My Dad is a retired civil engineer and unfortunately for him recently suffered a severe and itchy allergic rash on his legs caused by exposure to a biological washing powder.

After trying a topical antihistamine cream Dad went to his GP who prescribed antibiotics then, as a last resort, a steroid cream known as Betnovate-C.

According to the information leaflet accompanying the tube of cream it ‘may stain hair, skin, or fabric’. So, what’s it doing to your skin, my Dad wondered.

That aside, after a successful treatment, he was a bit puzzled as to how wash out a particularly stubborn mark on the bedsheets. His mind was put at rest by the instructions on the cream’s leaflet – ‘stains may be removed with a biological washing powder,’ it said.

Of course.

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.

Touch Wood! A Guide to Viagra Louts

Elephant penis, photo by David Bradley
When it comes to keeping up appearances, even a bucketful of gooey oysters, half a dozen XXX videos and a smattering of sensual massage don’t always have the desired result. In desperation, even tiger penis tea and rhino horn – is it hung round the neck, or what? – sound more appealing than the best medicine had to offer those who are willy nilly: a drug to circumvent the problem injected straight into the penis through the front opening in one’s underwear. A romantic interlude before lovemaking I don’t think. More a case of ‘take away the pain Doctor, but leave the swelling’.

Then along came Viagra – which was just swell! A solution, or rather a pill, for that little bedroom engineering problem. Medical science had come good, providing a much-needed boost for flaccid men the world over. With medical approval in hand, pharmaceutical company Pfizer launched their product on to a desperate market shooting to number one almost overnight. Prozac? Who needs it when Viagra gets to the root?

The story began several years ago when scientists found a tiny gas molecule called nitric oxide (NO) acting as a chemical communicator in our cells. Importantly, for sexual health, the release of NO by cells in the penis activates an enzyme called guanylate cyclase. This crucial reaction makes another molecule, cyclic guanosine monophosphate (cGMP). CGMP relaxes penile smooth muscle allows the arteries to expand and so blood rushes in giving an erection.

Horny old goat, photo by David Bradley

Normally, a second enzyme (PDE5 found mainly in the penis) gradually breaks down cGMP so without continued stimulation an erection flops. Pop a Viagra though and this second enzyme is blocked. Even the most flaccid of penis will release some NO with erotic stimulation and once it does there is no PDE5 available to damp it down again and for two-thirds of men erection will ensue – within an hour.

Viagra, aka sildenafil citrate, was originally to be a drug for treating angina and high blood pressure. When patients failed to return spare tablets after the clinical trial, though, Pfizer suspected something was up. It turned out that one side-effect was a spontaneous and sustained erection. Pfizer grasped the potential in treating what the doctor will call erectile dysfunction – ‘not getting it up’, to you and me. After the usual safety checks, they carried out a trial on more than 3000 patients aged 19 to 87 to see what effect the drug would have on impotent men and whether it could help them achieve a satisfactory sexual result. Rather than use video cameras to monitor ‘activity’, Pfizer opted for a questionnaire approach and trusted the patients, to be honest.


The responses tallied with anecdotal evidence from the heart patients: Viagra gets it up regardless of problem, general health, race, or age. The amazing thing is that Viagra gets it up in four out of five men regardless of why they are limp. There are so many causes of impotence, from psychological and old-age to injury and prostate problems, that a drug aimed at curing any one problem may not have been so successful. Viagra, or to give it its proper chemical name 1-{[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl}-4-methylpiperazine citrate (here is the pdb file), is satisfaction almost guaranteed despite the name being more of a mouthful than the tiny sky-blue diamond tablets.

Viagra has been available in the USA on prescription since March 1998 and, according to George Dunea of the Cook County Hospital in Chicago writing in the British Medical Journal that year, has probably led to a lot of doctors there with writer’s cramp pumping out almost two million prescriptions! Shares in Pfizer quickly reached a high plateau and should be sustained with anticipated billion dollar sales for next year – sex truly does sell.

Everything in the bedroom is not rosy though – far from it. One bizarre side-effect experienced by some users is a strange blue-green hue to their vision. The colour blindness passes but aside from jokes about too many erections making you blind, some eye specialists are worried about long-term effects on sight. Viagra has also been blamed for headaches, hot flushes, rash, dizziness, diarrhoea, priapism (sustaining an erection for hours after orgasm) and Pfizer provide an even longer list in the accompanying notes.

There is also the tragedy of sixteen men who have died while allegedly using the drug. Eight others died during the clinical trials. There is concern that simply resurrecting your sex life with a drug could have been the cause, with hearts pumping blood to places it has not been for a while. Most victims were in their sixties and seventies, and most had heart problems or diabetes. Although this does not prove that Viagra may have side-effects on the heart – Pfizer’s clinical research found that reduced blood pressure could occur.

Another problem has reared its ugly head too. It did not take long for people to realise that if Viagra can boost the ego, so to speak, of impotent men, then it could probably double the efforts for those without problems. Healthy men claiming impotency may be among the biggest beneficiaries of those millions of prescriptions. Popping a Viagra in the hope of giving even an active sex life that extra rise.

Not surprisingly, an Internet blackmarket quickly emerged with genuine Viagra as well as dubious products called Veagra and Viagre being marketed. Viagra is fast becoming a recreational drug and the UK’s Medicines Control Agency has even set up The Special Enquiry Unit of ‘V-men’ to hunt down anyone illegally selling Viagra. Once Viagra is made available on the NHS later this year, the government has said that individual GPs will be responsible for making sure only needy patients are prescribed it and they will be responsible for the outcome. There have already been more than a dozen attempts to market Viagra illicitly in Britain.

With abuse of drugs come increased risks, especially for particular users. Certain social groups have known for many years that a group of compounds known as organic nitrates (amyl nitrate/nitrite, or poppers, are probably the best known) can speed your pulse, boost libido and allegedly make sex a more fast-paced and thrilling experience. While there are numerous nitrate-based prescription drugs too for treating hypotension including some based on nitroglycerine – the opposite of high blood pressure. The problem is that anyone taking these drugs with Viagra could suffer plummeting blood pressure and possibly death. There have been reports of patients taking nitroglycerine treatment for low blood pressure who have experienced blackouts but doctors are warned to check for other medications and drugs before prescribing Viagra.

But what about the ladies? Pfizer is currently carrying out trials in Europe and discussions are taking place in the US to see whether women with sexual dysfunction, reduced libido, or lubrication problems (which can start at menopause) might benefit from taking the drug. There is now evidence that male erectile dysfunction might be more closely related to similar problems in women where blood flow to the genitals is just as important in sex. What’s sauce for the goose…after all.

There could soon be an alternative to Viagra. Vasomax (phentolamine) made by Zonagen is still passing through the approval pipeline. It apparently has the distinct advantage over Viagra in having only a 20 minute pre-love period. It’s also safer for patients taking nitrates. Pfizer, of course, intend to pre-empt approval of Vasomax and are working on a wafer form of Viagra that would be absorbed through the tongue and so act much more quickly.

The Public Health Minister Tessa Jowell has announced that Viagra will be available by prescription this year, but declined to say how the prescriptions would be limited and exactly how patients would be assessed for need.

Anyone, thinking about Viagra must weigh up the risks. The best bet might be to give the soft lights, romantic music and oysters another try. If you do opt for Viagra just pray you don’t discover you suffer from premature ejaculation…

Article by David Bradley

Science Writer originally appeared in the BBC Tomorrow’s World magazine.

Footnote added subsequently: But, what about the question of dissolving it in water? Sildenafil citrate is orally available, so presumably it dissolves in water but I doubt the manufacturers will be creating a fizzy version any day soon.

Since this article was first published several other drugs have come available – Cialis, Levitra, Uprima (goes under the tongue, sub lingually as it were), and new delivery methods for Alprostadil.