Lock up your hydrangeas, drug thieves about!

Hydrangea hortensis smith

Plants are rich and varied sources of chemicals that change brain function, so-called psychoactive chemicals. For example, the coca plant, a shrub indigenous to the foothills of the Andes, was used for thousands of years by the local people because of the effects of the cocaine contained in the leaves. The peyote cactus has been used for millennia by the inhabitants of Mexico and Central America to experience the psychoactive effects of mescaline. In the 19th century, many families living in the Fens in the East of England grew a stand of white poppies in a corner of their garden. These were harvested to make a “poppy-head tea” containing small amounts of opium. The tea was used as a traditional remedy for the various ailments that afflicted rural life in that part of the UK.

These are just three examples but they illustrate the ingenuity of humans for finding plants that have interesting or useful properties when consumed. For every flower or plant, someone, somewhere will have tried eating it or smoking it and, if they survived, they will have reported the effects.

Hydrangea May 2012-1

I was, therefore, more than surprised when, last month, I read a Guardian leader “In praise of hydrangeas” which not only extolled the plant for its blooms but also pointed out the recent discovery of the psychoactive properties of the flowers. According to a companion piece there had been a spate of hydrangea attacks in northern France, attributed, so the article alleged, to people wishing to smoke the dried flowers and leaves because of the hallucinogenic and euphoria-inducing effects which are similar to those of cannabis. The thieves must be after the new shoots judging from the state of a hydrangea in my garden; it has plenty of new growth but the few flowers left are dry, brown and rather mangy.

I hadn’t heard of the psychoactive properties of hydrangea before and didn’t know quite what to make of the story. It sounded worthy of April Fool’s Day but in fact the craze for smoking hydrangea is not new and springtime hydrangea theft has been known in Bavaria for more than 10 years. In Romania, they are so concerned that they have stopped planting the shrub in parks.

Hydrangea does not feature in my pharmacognosy textbook suggesting that if hydrangea does possess any interesting pharmacological properties, these have been overlooked. Nevertheless, the shrub does contain some unique chemicals including the coumarins, hydrangine and hydrangenol but unfortunately no psychoactive properties have been reported for these substances. Importantly, hydrangea does not contain compounds typical of cannabis such as tetrahydrocannabinol.

So what’s going on here? It doesn’t look as though there are major psychoactive chemicals in hydrangea so how does smoking the shrub produce a high? Perhaps we can get a clue from veterinary reports on the dangers of hydrangea to pets. Apparently dogs and cats can become unwell if they eat the leaves. This is attributed to chemicals found in hydrangea called cyanogenic glycosides which can break down, when metabolised, to produce the very poisonous substance, hydrogen cyanide. Cyanogenic glycosides are found in many different plants including some apricot kernels and almonds, also apple and cherry seeds.

Hydrogen cyanide is very poisonous to humans as it inhibits energy production in cells. Some of the short term effects of cyanide are headache, dizziness and confusion. Perhaps when leaves or flowers of hydrangea are smoked, small amounts of hydrogen cyanide are released. Consumption of one hydrangea joint might, therefore, provide a little cyanide and the effect, combined with a good dose of imagination could be interpreted as cannabis-like. This would also fit with the many warnings about not smoking more than one hydrangea joint because of the significant risk of cyanide poisoning.

I have not come across any reports of hydrangea smoking in the UK but I did find a report of bloom theft in Hastings and Bexhill in 2012. Apparently, the thieves were then selling the dried blooms to flower arrangers at a boot fair. At least that’s what they said!

I should like to thank Dr Ben Whalley (University of Reading) and Prof Kurt Hostettman (University of Geneva) for helpful discussions.

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Relative oblivion and revivals

Image of Penny Candy paperback edition, by Jean Kerr

Penny Candy paperback edition, by Jean Kerr

While on vacation in California, I had the U.S. version of a famous online bookstore locate and then send me a copy of a collection of essays I once enjoyed in the very same yard-sale paperback edition. It is as old as I am, and entitled Penny Candy, by Jean Kerr. Back when, this book enabled me share other people’s experiences in a world rather different from my own, with the same efficacy and novelty as any Emily Brontë or Lois Lenski novel.

Rereading the brittle, acid-yellowed pages with nostalgic pleasure, I was immediately struck that some of the shorter essays, like the one I will transcribe below, would have made wonderful blog posts. I then went to find this particular one online, to discover that it is not easy to dig up – its original publication was in the Dramatists’ Guild Bulletin, an erstwhile publication of the Authors’ League of America, before being reprinted by Fawcett Crest [(c) Collin Productions, Inc.]. To my disappointment, the essay I had in mind has been reduced to being “a great quote” of its author, and its actual content apparently buried under many hundreds of millions of other English-language blogs, editorials and opinion essays.

So, I will consider that I have performed my requisite sourcing, and with no further ado, here I revive for the Internet annals:

I Don’t Want to See the Uncut Version of Anything
by Jean Kerr

Subtitled: “Reflections of a Part-Time Playwright*

Recently, I was heard to murmur against the endless frustrations connected with getting a play produced. I mean I was exploding in all directions and pounding on the table with the handle of a broom. My husband finally quieted me by saying, “How can you complain so much – do you know that Euripides was exiled?” Actually, I didn’t. But now that I know, it makes all the difference. In the future when shadows gather and vexations mount, I shall take solace from the fact that, in any event, I was never exiled.

But I don’t mean to talk about playwriting. My experience as a playwright is so limited that I think it would be hasty for me to theorize about it*. On the other hand, because of my husband’s sorry occupation, my experience as a member of the audience is enormous. It occurs to me that in the last eighteen years I have become the most experienced audience in America.

We are agreed that a critic is not, and never will be, a member of the audience. Not only is he paid to attend, he is paid to listen; and this sobering circumstance colors his whole attutude toward the material on stage. The critic says: This is an extremely bad play – why is that? The audience says: This is an extremely bad play – why was I born? There is a real difference.

Anyway, on those melancholy opening nights when one sees that the jig is up and the closing notice soon will be, I make little notes to myself. I list some of them here in the wistful hope that somewhere there is a beginning playwright who will believe that my prejudices are shared by some other people. I think they are. I think I am pretty close to being the square root of the ordinary audience. I notice that I perk up when other people perk up. I slump when they slump. And I most certainly do not keep my head when all about me are losing theirs. I think paradise will be regained on 44th Street when young playwrights understand that they must try not to write plays that will cause nice, ordinary people from Riverdale to wish they were dead.

Little Notes to Myself:

I believe that plays that are successful are almost invariably more entertaining than plays that fail. This will come as a revolutionary idea only to those who have spent their lives avoiding beautiful girls because they are rumored to be dumb.

It is perfectly all right with me when a character in an avant-garde play points to a realistic iron bed and says, “That is a piano.” It is still all right with me when another character sits down in front of the bed and plays The Blue Danube Waltz on the mattress. But thereafter I expect that nobody will lie down on the piano.

I think that if there are only three characters in a play, one of them ought to be a girl.

I do not wish to see musical comedies performed entirely on bleachers in which the leading man wears clown-white make-up (the only man in the world who can put on clown-white make-up and be Marcel Marceau is Marcel Marceau).

It strikes me as less than hilarious when an actor, impersonating a foreigner, is required to struggle with our quaint American colloquialisms. (“How ess eet you put it? I shovel you. Ah, no. I deeg you.”)

I do not like to hear the most explicit four-letter words** spoken from the stage because I number among my acquaintance persons of such candor and quick temper that, for me, the thrill is gone.

I have noticed that in plays where the characters on stage laugh a great deal, the people out front laugh very little. This is notoriously true of productions of Shakespeare’s comedies. “Well, sirrah,” says one buffoon, “he did go heigh-ho upon a bird-bolt.” This gem is followed by such guffaws and general merriment as would leave Olsen and Johnson wondering how they had failed.

It may have been bearable the first time it was done, but it is no longer bearable to see a comedy in which the ingenue yap yap yaps the whole first act long about the burdens of her virginity.

Images of brunch coats.

Brunch coats. They make everyone look terrible.

Also – speaking of the same kind of play – the heroine always does look as cute as all get out when, for reasons of the plot, she has to wear the hero’s bathrobe. On the other hand (and this is happening more and more), when the hero is required to wear her brunch coat, he looks just plain terrible.

I have noticed that an entertainment that opens or closes with the setting up or dismantling of a circus tent always gets good notices***. I don’t know what to make of this.

I have seen plays performed on steps in front of a cyclorama that I enjoyed – but not many.

I am wary of plays in which God or the devil appear in characters. We will waive any discussion of theology and I don’t mean to be irreverent when I say that, for all practical purposes in the theater, God is a lousy part. (A play I really loved, The Tenth Man, had to do with a girl who was being exorcised of the devil, but it may be relevant to note that we never saw the devil.)

I don’t want to see productions that run four and one-half hours. (I don’t want to see the “uncut” version of anything.) In a recent production of King Lear, the first act ran for two and one-half hours. By that time I considered that I had given up smoking, and I spent the entire intermission wondering if I should begin again. And I was once more made aware – during that interminable first act – that the most serious materials eventually seem comic if they are allowed to go on too long. For instance, during the protracted scene in which Lear (now mad) is talking to poor, blinded Gloucester, all I could think was: first they put his eyes out, now they’re going to talk his ears off.

One thing, though. Whatever their losses on other fronts, actors have got to keep their teeth in. I would have thought this went without saying until I saw two plays by Joe Orton. In one a slatternly landlady, who was competing with her brother for the affections of a male lodger, lost her dentures under the sofa. In another, a young man plundered the corpse of his recently dead mother, removing her false teeth so that he could use them as castanets. If this sounds funny, I’m not telling it right.

When The Little Foxes was revived recently, there were those who said it was too well constructed. To me, that’s like saying a Pan Am pilot is too conscientious. What I like about Lillian Hellman’s play is that you couldn’t play the second act first. I know all about improvisation and the free-form that mirrors the chaos of our time, but I do like to feel that the playwright has done some work before I got there.

I dislike seeing actors perform in the nude. Not that, at my age, I am shocked, but I become exceedingly uncomfortable as the naked performers begin to perspire under the hot lights and develop a tendency to stick to the furniture, or, worse, to each other. In the aura of silliness which prevails on such occasions, I find myself distracted from the plot (which seems merely to be against the audience) into practical considerations. Do they still call them dressing rooms? If an actor develops a boil in an unsuited area, is a Band-aid used, or the understudy? Is it possible to say to an actor, “I saw you in Oh, Calcutta!,” without laughing?

At plays like A Man for All Seasons, The Matchmaker, The Lady’s Not for Burning, A Streetcar Named Desire, The Odd Couple, The Great White Hope, Summer and Smoke, and The Front Page, I don’t make any notes at all. I just sit there and bask and bask and bask and then, when the glow begins to wear off, I go back again.


* see her biography … multiple essay collections, a particularly rich and busy family life, no computer, and enough plays to qualify as full-time in my book.

** “Good authors too who once knew better words, now only use four-letter words. Writing prose, anything goes.” Cole Porter, Anything Goes (1934)

*** Kerr may be referring to J.B. among others, which was relatively appreciated by her husband.

Posted in Art, Fun | 4 Comments

Research talks about large congenital melanocytic nevi

Cross-posted from The Node:

Limited time offer until 30 April 2014. Read on.

CMN-NCM conference

As a developmental biologist, I have found my calling in applying what I have learned  about normal embryogenesis to better understanding the pathophysiology of various  human congenital malformations. Often these are rare diseases, and I work closely with patient associations devoted to those conditions and learning to live with them (or with the death of the child who had been afflicted).

Among these, the congenital melanocytic nevus (CMN) is one in which I have been interested for the longest time. I organized a conference last fall in Marseille specifically devoted to the basic biology, epidemiology and medical and psychological considerations around the largest and rarest forms of CMN. I have also assisted the existing worldwide patient groups to federate, which will help us help them build a prospective registry for further research.

I didn’t do it alone, of course. Mark Beckwith from Nevus Outreach, Inc. was the most active, and the only non-physician, member of my organizing committee. We innovated by asking all the speakers to make their presentations available online, behind an inexpensive but secure paywall, and by dubbing the presentations with the sound of their actual delivery. In some settings, this is known as a slidecast. The slides advance automatically in sync with the sound.

We also placed the videos, when relevant, of the Q&A periods following the talks. The titles of the talks in the programme are at this link, and the PDF with the abstracts and titles can be downloaded directly from this one.

The idea was to make a resource that would slowly garner hits over time, as I have done with some of my teaching in the past. However, the company hosting the slidecasts has decided to eliminate the slidecast offering for good, after seven years, in the next three months. After I paid for a subscription for a full year, of course.

So: 33 presentations from the ESPCR-sponsored International Expert Meeting on Large Congenital Melanocytic Nevi and Neurocutaneous Melanocytosis in September, 2013, are currently available online. They are web-viewable “slidecasts” (author-approved slideshows with synchronized sound from the live presentations). In addition, there are 29 videos of the corresponding question and answer sessions. The slidecasts disappear at the end of April, 2014.

You can virtually “attend” this conference for only 25 euros (approximately 35 USD or 21 GBP) by navigating to this webpage. All proceeds will directly support building a prospective patient registry by the Naevus Global international federation of advocacy groups. I’m writing this to ask you to support a worthy cause and consider learning about the direct result of the developmental biology of a neural crest derivative, gone wrong in one particular molecular way (I’ll let you discover which).

After secure payment through PayPal using either a PayPal account or a credit card, we hand-distribute unique identifiers and the address of a restricted part of the Naevus Global site. There, the order of the program is reproduced, with hyperlinks to the slidecasts and videos.

Thank you for your budding interest in current research on congenital melanocytic nevi & neurocutaneous melanocytosis! I hope you find this resource beneficial and informative, and that you will support our patient registry initiative in this manner.

Sincerely yours,

Heather C. Etchevers, Ph.D.

P.S. Added on 7 February: This is a mouse blood vessel along the underside of the forebrain, with a little cuff of melanocytes – black – instead of smooth muscle, though all of both kinds of cells in theory are carrying the same mutation that is commonly found in human CMN.

We can get some pretty black brains in this manner, but that’s not what kills the mice who end up dying. They’re not a perfect model for the human condition, partly because they’re not human.

But we all have a few pigment cells normally in our meninges (and heart valves, and some other odd sites), and the mice are no exception.

Posted in Conferences, Education | 6 Comments

A night at the opera – or how the myth of the love potion seduces both writers and scientists

The Glyndebourne Touring Opera visits Plymouth in the South West once a year and it’s a real treat to go to their productions. This year we went to see Donizetti’s frothy but very popular L’elisir d’amore. This was beautifully sung and played by the young cast and the production, directed by Annabel Arden, was slick and sexy, with plenty of laughs and a few naughty bits. The story is slight: unsophisticated country lad, Nemorino wins the heart of knowing beauty, Adina with the help of “the elixir of love” sold by the travelling quack, Dr Dulcamara. The elixir is purported to make the drinker attractive to all members of the opposite sex but is actually only cheap wine. Despite the lightweight plot, it was a charming evening and Donizetti captured my attention for more than two hours with his ever changing melodies. Here is a link to some pictures of the production.

Donizetti is not the first to have been captivated by the idea of a “love potion” and we find the motif frequently in both myth and in literature. One of the earliest examples is the Celtic legend of Tristan and Iseult: Tristan is sent to Ireland to collect Iseult, already betrothed to King Mark. Along the way, Tristan and Iseult ingest a love potion and fall deeply in love causing all sorts of problems. Wagner used this story in his opera Tristan and Isolde and the legend surfaces again in L’elisir d’amore; Nemorino hears Adina reading the story and this gives him the idea of using a love potion to win her heart.

Other examples of writers using love potions as plot devices include Shakespeare’s A Midsummer Night’s Dream and Gilbert and Sullivan’s comic opera, The Sorcerer. JK Rowling used the idea in her Harry Potter books; her love potion, Amortentia causes powerful infatuation or obsession in the drinker.

It is, however, in a Hollywood movie that we finally see scientists confronting the love potion myth. The 1992 film Love potion number 9 introduces geeky biochemist Paul and his comparative psychobiologist colleague Diane; Paul has a secret crush on Diane but, as you might predict, his geekiness gets in the way. Paul is given a love potion by Madam Ruth, a gypsy palm reader, to help overcome his diffidence. He is sceptical at first but, when he sees the effect of the potion on the sex life of his cat, he enlists Diane’s help in “scientifically” analysing the potion; this includes shedding their lab coats and testing the love potion on themselves. The plot twists and turns, but all ends happily ever after for Paul and Diane.

Although the storyline in this movie is lighter than the foam on a perfect cafe latte, the idea of manipulating romantic attraction using a love potion is a perennially fascinating topic, which is why it continues to emerge as a plot device in fiction of all kinds. The same fascination may be what drives real scientists to investigate the basis of romantic attraction.

One of the more infamous scientific investigations in to the basis of romantic attraction is the so-called “sweaty t-shirt experiment” performed by the Swiss Zoologist, Claus Wedekind in 1995. Wedekind was interested in the factors that influence human mate choice and for his study he recruited a group of young men and women. The men were given t-shirts and asked to wear them for two days. At the end of that time the men were instructed to put their t-shirt in to individual but identical boxes. The women were then asked to smell the t-shirts and declare which they found most sexually attractive. Definite preferences were exhibited by the women in their choice of sweaty t-shirt suggesting that odour plays a part in male/female attraction. Moreover, Wedekind showed that the women tended to select men with dissimilar genes in part of the immune system (MHC complex). This could be a means of ensuring that potential offspring have a strong immune system.

Another, very recent, study from the University of Bonn examined a different aspect of romantic attraction, namely how the bond between loving couples is maintained. The work focussed on the role of the brain chemical oxytocin, dubbed the “cuddle hormone” by the popular media. Pair-bonded heterosexual men were shown pictures of their partner or of unfamiliar women. Before the pictures were examined, the men were given intranasal oxytocin or placebo and neither the subjects nor the scientists were aware of the treatments.

After receiving intranasal oxytocin, the men perceived their partner’s faces as more attractive, and there was no such effect when pictures of unfamiliar women were presented. The enhanced partner response was paralleled by activation of the brain’s reward system in a manner similar to that produced by some drugs. The authors concluded that oxytocin contributes to romantic bonds for men by enhancing partner attractiveness and so may contribute to human monogamy.

You can imagine that these kinds of studies might, in the future, lead to forms of love potion but based on another piece of fiction, we might want to be wary of the consequences. In 1974, Roald Dahl published a slightly risqué and slightly unpleasant book called Switch Bitch consisting of four short stories. One of these stories describes the efforts of Belgian olfactory chemist, Henri Biotte, to make a perfume, the ultimate love potion, which activates the nasal receptors corresponding to the eighth human primary odour, for sexual desire. His synthetic odour does what he expects it to do but when his co-worker sprays it over herself, Henri gets overexcited and suffers a heart attack as a consequence.

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The bitter wind of Brussels sprouts

It’s that time again; that most controversial of vegetables is appearing in UK shops. I am referring of course to Brussels sprouts, feared and hated by some, lauded by others. Not only is it peak growth season for sprouts but, for reasons that are obscure to me, it has become traditional for many families to include Brussels sprouts as part of their December 25th lunch menu. The upshot of this is that a quarter of the annual UK consumption of Brussels sprouts (40,000 tons in total) occurs in December.

Brussels sprout closeup

So, what is it about this humble vegetable that raises such passion? Speaking personally, and I would guess this is true for others, I have never fully recovered from the childhood experience of overcooked boiled sprouts, bitter, sludgy, sulphurous and barely green. Part of the problem is that brassicas and particularly Brussels sprouts contain bitter tasting compounds called glucosinolates. These sulphurous compounds are thought to act as natural pesticides protecting the plant from insects. Humans find the glucosinolates bitter and this contributes to the bad reputation of sprouts. Worse still, when sprouts are boiled, glucosinolates are released in to the cooking water where some break down to smelly sulphurous compounds and that’s the odour we all remember. Much of the odour problem can be avoided by following Nigel Slater’s maxim: “The trick is to keep them well away from boiling water”.

To be fair to sprouts, they do not taste bitter to everyone and this variation seems to be, at least in part, down to genetics. As long ago as 1930, it was realised that the ability of humans to taste bitter substances had a heritable component. People who could detect bitter substances were very likely to have other family members with the same ability. The family link was so strong that it was used as a paternity test before DNA testing was available. Now we know that detection of bitter taste depends on both the number of taste buds on our tongues and the presence of particular isoforms of receptors on the taste buds that detect the bitter substances. As a result some people taste the bitterness of Brussels sprouts more than others, accounting in part for the differences in opinion about the vegetable. Children also seem to have a greater ability to detect bitter taste compared to adults so perhaps they are not so annoyingly fussy after all. The bitterness of sprouts may, however, be a thing of the past as the agrochemical companies have been working hard to breed new sweeter varieties, one of which is on sale this Christmas.

There is a further and perhaps even darker side to sprouts: the “windiness” that some people experience after eating Brussels sprouts. You probably didn’t want to know this but Sainsbury’s has compiled a “Top of the Pops” of windy vegetables: sprouts made third place beaten only by Jerusalem artichokes and parsnips. According to the Naked Scientists, the “windiness” of sprouts arises because our stomach and small intestine lack the molecular machinery to digest them fully so they arrive in the colon only partially digested. Bacteria in the colon do contain the correct chemical scissors so they set to work on the sprout remains and produce gas. To add to the problem, when the sulphurous compounds in sprouts are broken down they lend the gas an unpleasant odour. I leave the rest to your imagination or experience.

A growing band of sprout supporters, however, ignore the windy bitterness in favour of the health-promoting properties of these mini cabbages. In particular, they hail sprouts for their high content of both vitamin C and vitamin K. We are all urged to eat fruit for its vitamin C but sprouts contain, on a weight for weight basis, twice as much vitamin C as oranges. Vitamin K is not so well known but it plays an important role in blood clotting, facilitating wound healing; it may also help build strong bones. Green leafy vegetables, especially sprouts, are good sources of this essential nutrient. For most people, the high vitamin K content of sprouts is a healthy bonus but it can cause problems if you are taking anticoagulant drugs. An extreme example of this effect occurred to an Ayrshire man with a mechanical heart who was taking anticoagulants to prevent blood clots. In December 2011, he was rushed to hospital because his anticoagulants had stopped working. Apparently he had eaten a large plate of Brussels sprouts and the pro-coagulant vitamin K had counteracted the effects of his drugs.

Lastly some Brussels sprout trivia:

The Guinness World Record for eating the vegetable is held by Linus Urbanec of Sweden. To win the record, he ate 31 sprouts in one minute!

Francis Crick met his second wife, Odile in 1945 when she spilled a bag of Brussels sprouts on the floor of the office where he was temporarily working. He helped her pick them up, asked her out and was refused.

Sprouts grow on their stalk in a helical pattern as shown in the picture below. Perhaps Crick’s unexpected encounter with Brussels sprouts gave him an early clue about the structure of DNA!

Verlinghem choux de bruxelles

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Old Nutt’s new fangled Ale

Deck the hall with boughs of holly
Fa la la la la la la la la
‘Tis the season to be jolly
Fa la la la la la la la la

Christmas may still be several weeks away but there’s no shortage of people urging us to be jolly. Our local baker has been selling mince pies since early November and one of his fastest selling new lines is a mini Christmas pudding cake decorated with marzipan holly leaves. Our weekly vegetable box arrives stuffed like a Christmas turkey with leaflets encouraging us to buy festive meat, cheese, chocolate and wine. Despite all these signs, I was surprised to see a large advertisement in the Guardian (November 15th) for cheap booze from Tesco. The ad was decorated with Christmas ribbon and offered, for a few days, 40 cans of Fosters Lager or Strongbow Cider for £22. The small print told me that this offer was not available in Scotland; this is because in Scotland these cheap multi-buy offers are banned in an attempt to cut back on problem drinking. But Tesco are responsible people and the ad included a referral to drinkaware.co.uk “for the facts”.

We have big problems with alcohol misuse in the UK. There are as many as a million alcohol-related hospital admissions each year; alcohol fuels crime and civil disorder and is estimated to cost the economy up to £20 billion a year. The health effects of alcohol abuse were illustrated starkly to me by a recent account of a 35-year old woman from Middlesbrough with cirrhosis of the liver so serious that her only hope is a transplant. Her liver damage arose from just two years of heavy drinking (up to 3 bottles of wine a day) superimposed on low-level regular drinking. She is not unique and clinicians in the North East have noted an increase in the number of under 30 year olds being admitted to hospital for alcohol related liver disease: 23 were admitted in 2003 compared to 115 in 2012.

Someone who speaks out about the problems of alcohol abuse is David Nutt, also well known for his strident views on the drug laws. Following his 2010 study on the harms of different drugs he bravely labelled alcohol as being even more damaging than heroin or crack cocaine. He was recently awarded the John Maddox Prize for Standing up for Science. He has been speaking up again and in a Comment piece for the Guardian he proposed replacing alcohol with synthetic alternatives in order to reduce harms. I want to look at his proposal in detail.

First, a bit of background. David Nutt’s target for his alcohol substitutes is a brain protein called the GABAA receptor. This receptor is the normal physiological site of action of a brain chemical (GABA) which tends to damp down brain activity. It is also an important, but by no means exclusive, site of action of alcohol in achieving its relaxant/sociability effects. The GABAA receptor is also the site of action of drugs such as Valium (diazepam), used to calm anxiety. Diazepam is a member of a large family of drugs called benzodiazepines and diazepam itself binds to the receptor at a site separate from the natural chemical GABA and increases its effects. In this way, diazepam damps down brain activity reducing anxiety, but also causing sedation and sleepiness; tolerance can also develop and is a serious problem.

Benzodiazepines are abused by some people who take them to achieve a “high” which includes feeling energetic, relaxed, drunken, talkative and euphoric. This sounds rather like the effects of alcohol and shows that, in principle, a drug related to diazepam might take the place of alcohol. The tendency for diazepam to cause tolerance and dependence means that in designing any alcohol substitute, substantial molecular tinkering would be needed to remove the potential for addiction.

The pharmaceutical industry has been very busy over recent years making all sorts of benzodiazepine derivatives as potential drugs. One group of compounds exhibits partial or selective activation of GABAA receptors when compared to diazepam. The partial/selective activators were developed in the hope that they would calm anxiety but produce less sedation, although none has been marketed.

Another class of compound binds to the benzodiazepine site but does not alter the activity of GABA. In principle, these should interfere with the effects of the other benzodiazepines. The proper pharmacological term for these is antagonists.

These two kinds of compound are, I believe, the drugs that David Nutt has in his sights. He proposes to develop alcohol replacements based on the partial/selective activators. They would probably produce some of the desirable aspects of alcohol such as relaxation/sociability/ inebriation without the unwanted effects such as liver and brain damage because these effects occur via mechanisms not associated with the GABAA receptor. They may lack the tolerance/dependence/overdose problems. They would be available in drinks at bars or possibly in pill form at pharmacies.

He also proposes to include the antagonist compounds in his cocktail cabinet. The antagonists should, in principle, terminate the actions of the partial activators. So, in Old Nutt’s Tavern, when we are ready to go home we take the antagonist drug and sober up directly.

Although this proposal has attracted considerable interest, it is not a new one. Nutt first proposed it seven years ago in a Critique in the Journal of Psychopharmacology. The current flurry of activity is a kite flying exercise to try to drum up financial interest and, I suspect, also to stir up some general discussion about alcohol. Nutt says he has five compounds ready to test in humans but it is important to be clear: no drug is currently available that would substitute for alcohol and we should not underestimate the time it would take to develop and test these new compounds. It would also be a major legal and social departure to develop lifestyle drugs as opposed to medicines.

I have several other queries about the approach. Will the effects of the compounds be acceptable to those who currently use alcohol? We have no idea but it seems unlikely that the GABAA receptor is the sole mediator of the positive effects of alcohol so that the proposed alcohol substitutes may lack something. Nutt says he has taken one of the proposed substitutes and he felt “quite relaxed and sleepily inebriated for an hour or so”. He then reversed the sensation by taking an antagonist, and successfully delivered a lecture. Will feeling “relaxed and sleepily inebriated” really be what people want? It all sounds a bit tame.

But let’s assume that the psychological/physical effects will be sufficient. I can then see that for people who consume mixed drinks such as cocktails and alcopops the approach might work. For those who currently “pre-load” with cheap alcohol before going out, a pill might be acceptable. I can’t, however, see this satisfying the wine buffs and real ale fanatics.

I also find it quite difficult to imagine someone in a bar, inebriated on one of these alcohol substitutes, meekly making the decision to go home and taking the antagonist to sober up. Would they really hop in to their car and drive home? Would we want them to?

How would the manufacturers of alcoholic drinks view this idea? I suspect that profit will be the driver. While society finds alcoholic drinks and their consequences acceptable, the drinks manufacturers will either ignore or oppose development of alcohol substitutes. Should society change its view and should acceptable alternatives become available then I would expect the drinks manufacturers to embrace the new technology.

If all of these questions can be addressed and, if a safe, efficacious and acceptable alcohol substitute were to be developed, then this would substantially reduce alcohol-related disease – that would be a great step forward. However, we are not going to see this in the near future so we should be looking at other ways to reduce harms and here reduced alcohol consumption must surely be the goal. The coalition government recognised the problems that alcohol was causing and in 2012 published its Alcohol Strategy. One of the key proposals was minimum unit pricing to curb binge drinking. The strategy document contains a strongly worded introduction from David Cameron supporting the approach. Despite this, the idea of minimum pricing was subsequently dropped, most likely because of pressure from the drinks manufacturers. This U-turn has been heavily criticised by many and some local councils believe so strongly that minimum pricing will control problem drinking that they have imposed the idea. Most notably, Scotland has passed legislation with a minimum 50p unit price for alcohol, although this has not yet begun.

The government’s Alcohol Strategy emphasised the relation between alcohol price and alcohol consumption. That is why it initially supported the idea of minimum pricing to curb consumption. It’s disappointing to see Tesco, one of the major UK supermarkets, advertising in the Guardian and offering promotions which equate to a cost per unit of alcohol of 31p for the Fosters lager and 25p for the Strongbow cider.

Michelangelo drunken NoahDrunken Noah (Michelangelo)

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Those poor beleaguered bees! Now they’re being confused by diesel fumes. Or are they?

honeybee on lavender 3

Bees are having a hard time. Pathogens, insecticides and loss of habitat are all thought to be contributing to a decline in their numbers. Now a potential new threat has been added to the “perfect storm” threatening these insects. A group at Southampton University recently reported that diesel exhaust could be affecting the ability of honeybees to detect oilseed rape. The work was widely reported in the press with headlines such as “Bees losing sense of smell because of traffic fumes”, “Diesel fumes confuse honeybees when foraging” and “Bees can’t sniff out flowers because of CARS: diesel fumes change the odour of blooms and could cause a global food crisis”

The report seemed to be at odds with the view that bees flourish in urban environments so I thought I should take a closer look. The work was lead by Prof Guy Poppy, an ecologist and Dr Tracey Newman, a neuroscientist. Their basic premise was that because honeybees use floral odours to find, identify and recognise flowers for forage, anything that interferes with this process may affect the ability of bees to forage and may impair survival. Diesel exhaust might interfere with detection of these floral odours so that’s what they investigated.

What they did was to create a synthetic odour corresponding to the principal chemicals in the fragrance detected by bees from oilseed rape flowers. They used this synthetic odour to examine the effects of diesel fumes and found major effects. Within a minute, two of the component chemicals were completely destroyed when the synthetic odour was mixed with diesel exhaust. The reactive species in diesel exhaust thought to be responsible for these kinds of effect are nitrogen oxides, so next they mixed the synthetic odour with a mixture of nitrogen oxides chosen to mimic levels in diesel exhaust. The same two chemicals were destroyed by the nitrogen oxides. Finally, they checked to see if these effects of diesel exhaust made any difference to the bees. Using immobilised forager honeybees trained to recognise the synthetic odour, they showed that depletion of the two chemicals lead to a ~70% reduction in detection of the odour by bees.

Superficially, this sounds very clear: diesel fumes destroy chemicals in the synthetic odour and, as a result, bees lose the ability to detect the odour. This could have major knock-on effects for bees’ survival. However, before I add diesel exhaust to my list of bee threats, I want to be assured that this study is relevant to real roadside situations or locations where oilseed rape is grown.

It’s here that the study runs in to some problems. The diesel exhaust used in the experiments came directly from a diesel generator. Helpfully, the paper gives the figures for the levels of nitrogen oxides in the exhaust and it turns out that it contained nitrogen oxides ~200 times higher than the ambient levels recommended in the EU and US. The levels in the exhaust are also ~200 times higher than those found in inner London and ~2000 times higher than in remote rural locations in the UK. Because the levels of nitrogen oxides in the exhaust are so high, I don’t believe these experiments are relevant to real roadside situations.

The Southampton group did also test lower levels of nitrogen oxides and found lower effects (the key chemicals were both reduced by about half using levels of nitrogen oxides corresponding to inner London). I can’t, however, see any experiments in the paper on detection by bees of a synthetic odour depleted of the two chemicals by ~50%.

So, at improbably high nitrogen oxide levels, the loss of odour chemicals may hinder bees detecting the floral odour but we don’t know what happens when only 50% is lost and this is the condition that corresponds to ambient air recommendations and incidentally to levels found by roads in inner London. Without this information, I don’t believe it’s possible to conclude anything about the effects of typical inner city roadside levels of nitrogen oxides on detection of floral odours by bees; the study does not, therefore, warrant the dire newspaper headlines about effects of diesel fumes on bees. It’s also worth pointing out that most oilseed rape is not grown near inner city roads but in the countryside. Levels of nitrogen oxides and effects on bee foraging in these rural locations are likely to be lower still.

Perhaps it’s useful to reiterate the fact that bees do flourish in urban environments despite some pollution from vehicle fumes suggesting that they are not greatly affected by these pollutants.

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The UK and New Zealand: two very different approaches to the problems of “legal highs”.

In many people’s minds, the county of Devon is synonymous with cream teas, cider and summer holidays so it may come as a surprise to hear that Devon has its fair share of social problems. Over the past few months there has been a rash of incidents with so-called “legal highs”, drugs that mimic the effects of illegal substances but which are not themselves illegal. They are sold through “head shops” or via the internet.

Two of these incidents concerned teenagers: one smoked a mixture called King B and was hospitalised with a very high heart rate after suffering two seizures, another smoked a mixture called Bubble Bud and suffered a stroke. Elsewhere in the county, two men were hospitalised after taking a white powder called El Blanco. These events prompted Tony Hogg, the Police and Crime Commissioner for Devon and Cornwall, to urge local people to campaign for closure of the “head shops” selling these legal highs. Torquay’s Director of Public Health wrote to all GPs in the region warning them about the risks of the drugs.

Both King B and Bubble Bud are smoking preparations sold to mimic herbal cannabis. They will contain plant material laced with a synthetic cannabinoid drug. The synthetic cannabinoids are chemicals that act at the same sites in the brain as tetrahydrocannabinol (THC), the main active substance in cannabis. They produce the cannabis “high” but seem to be associated with a different range of adverse effects. Synthetic cannabinoids are different in structure from THC and several chemical series have been made. As of May 2013, 84 different analogues had been described in Europe reflecting the activities of labs in the Far East who make the chemicals. Some of these analogues have much higher potency than THC making them potentially much more dangerous; the high potency may account for some of the severe reactions reported. The response of authorities in Europe has been to ban the chemicals as they detect them. The labs in the Far East then supply a new cannabinoid and the cycle starts again. King B and Bubble Bud must have contained chemicals that are currently not illegal.

El Blanco is quite different and probably consists of ethylphenidate mixed with benzocaine. Ethylphenidate is a close relation of methylphenidate (Ritalin), a stimulant used to treat ADHD. Ethylphenidate causes release of the brain chemicals dopamine and noradrenalin leading to a cocaine-like euphoria. Benzocaine is a local anaesthetic and is probably included to cause numbing of the nasal passages when the drug is snorted, tricking the user in to thinking that El Blanco is cocaine.

People taking these “legal highs” are running huge risks for several reasons: the drugs are of undefined purity, the preparations contain varying amounts of the chemicals, the short and long term physiological effects of the chemicals are not well defined and none of the chemicals has undergone the kind of safety testing mandatory for a prescription medicine. Dubbing the preparations “legal highs” encourages people to feel they are safe whereas in fact the exact opposite is true. This is a new and very dangerous situation and we should look to novel ways to control it.

We may get some ideas from New Zealand, a country that has grappled with a similar problem and which has come up with new strategies to deal with “legal highs”. On July 18, the Psychoactive Substances Bill was approved by the New Zealand Parliament. This was a response to a situation that was out of control. Herbal smoking preparations (analogous to King B and Bubble Bud) had become hugely popular as cannabis substitutes. Although many of the chemicals had been made illegal, they were quickly replaced by new “legal” synthetic cannabinoids. Several thousand shops were selling the smoking preparations, many of these were convenience stores selling household goods like milk (the “dairies”) and there were few restrictions on who could buy the preparations. As one government minister commented, “It was the Wild West”.

The Psychoactive Substances Bill aims to wrest control back in to the hands of the authorities, but in a novel manner. The Bill accepts that people want to use these preparations but intends to reduce the volume sold and the risks to users. In the long term, manufacturers wishing to sell psychoactive substances will have to establish that the drugs are of low risk based on a comprehensive set of safety data that they must acquire themselves.

Obtaining the safety data will take time so interim arrangements have been put in to place. The New Zealand government wisely took the view that a complete ban on sales of “legal highs” during the interim period would drive trade underground but new controls on their sale and manufacture have been introduced. Sales of “legal highs” are now restricted to specialist shops; sales from shops selling food or alcohol are prohibited. Only those over 18 may buy or possess the drugs. Manufacturers had to apply for an interim licence to supply and these were granted to substances deemed to be of low risk, based on a clear set of criteria. Several preparations failed to meet the criteria as they were deemed to be of too high risk. Approved “legal highs” must be sold in packets carrying a health warning and a list of the active ingredients.

As a result of these changes, the number of outlets has fallen from several thousand to 110. There is a published list of approved, low-risk, smoking preparations that can be sold, each with details of the chemical contained. Given the “cloak and dagger” nature of drug sales in other countries, it is something of a revelation to see the nature and variety of the chemicals and the names of suppliers declared in this way.

The New Zealand government is either very brave or very foolish as they have created a situation whereby these “legal highs” are being sold with government approval. Quite what happens when someone becomes unwell or dies after taking one of these poorly characterised and poorly tested preparations, I am not sure. Indeed, there have already been protests in some parts of the country about the continuing sale of the compounds.

But before we rush to judgement, let’s compare what is happening in New Zealand under the new system with the existing state of affairs in the UK. In both countries, despite the difference in legal approach, people, especially young people, are using the “legal high” smoking preparations. In the UK, head shops are supplying these poorly characterised materials; we have little idea about what people are actually taking and how much and some people are damaged as a result. In New Zealand, following the change in the law, supply is via a limited number of licensed shops; the number of possible preparations has been reduced, the composition is listed and a rough idea of low risk has been established. New Zealand is making an attempt at controlling a difficult situation; only time will tell if it works.

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Next time you see Nelson’s Column, think of Dartmoor

Dartmoor is the largest and wildest area of open country in the south of England but despite the wildness, the human imprint is never far away. For many years, the moor has been exploited by industry which has shaped the landscape and continues to do so. We walked on the moor recently, and stumbled across surprising traces of Dartmoor’s industrial past and present. Even at our starting point, the car park near where Cadover Bridge crosses the River Plym, there were signs warning of the dangers of a disused china clay pit nearby.

We began by heading up hill towards Cadover Cross. This is one of many Dartmoor Crosses, made of local granite and thought to have been landmarks for travellers in this remote countryside often plagued by bad weather. Cadover Cross may have been associated with important 12th century routes that used the river crossing.

Cadover Cross, Dartmoor

The view downhill from Cadover Cross showing the bridge over the River Plym and wide expanses of open moorland typical of this part of Dartmoor. This was one of the landscapes used by Stephen Spielberg in the Warhorse. The spoil heaps of the disused clay pit are visible on the right.

View from Dewerstone Rock

View from Dewerstone Rock

Leaving the Cross, we continued over scrubby grassland interspersed with bracken and gorse, sharing the route with sheep, a few ponies and one cow. We kept the heavily wooded Plym valley on our left but we could not yet hear the river; the only sound was the gossip of a few passing birds. Eventually we reached the highest point on this walk, Dewerstone Rock, where traces of ancient settlements have been found. From the Rock, there were panoramic views towards the coast with Plymouth Sound clearly visible. On this dull, slightly misty day, it was just possible to make out the Wheel of Plymouth on the Hoe near where, according to popular anecdote, Drake played bowls as the Armada threatened.

Cut in to the rock, and now rather eroded, is the inscription

Obit Septembris

This is a memorial to the teacher and local poet Noel Carrington who died in Bath in 1830.

From Dewerstone Rock, we dropped steeply down through oak woods passing the remains of disused 19th century quarries and the bed of a railway that was once used to transport blocks of granite down the hillside. The rails have long gone but the sleepers, regularly placed granite blocks, and the fixing holes in some of the blocks were clearly visible.

Granite sleepers, Dewerstone Woods

Granite blocks forming sleepers of the old railway

Fixing holes on granite sleeper

Fixing holes in granite block from old railway

Granite forms the bedrock of the high moor and has been used as a building material for as long as humans have inhabited Dartmoor. Many local buildings including Dartmoor Prison and the large church at Widecombe used local granite and the material has also been used in London, notably in the old London Bridge (now in Arizona) and Nelson’s Column.
The path continued in zig-zags through woodland down the side of the river valley. We could hear the river before we could see it but eventually it was there, bubbling over rocks near Shaugh Bridge. This was the half-way point of the walk and a pleasant place for us to eat our sandwiches.

P91The River Plym near Shaugh Bridge

The river Plym near Shaugh Bridge

Having crossed the river Plym, we picked up the woodland path back to Cadover Bridge. Now, all around us were traces of a second Dartmoor industry, china clay mining.

China clay was first discovered in the UK in Cornwall in the 18th century, and has been mined continuously on Dartmoor since the mid 1800s. China clay, or kaolin, was originally used to make porcelain but nowadays it is used in many processes including the manufacture of paper, ceramics and toothpaste. Kaolin is a breakdown product of granite and, for many years was mined using powerful jets of water. The water washed out the soft kaolin in a crude mixture with stones, gravel and sand. After the coarse particles were filtered out, the kaolin slurry was put in to huge settling tanks. The compacted kaolin was then dried to produce blocks of china clay for transport.
In this part of the moor, the kaolin suspension was piped more than a mile from the now disused quarry near Cadover Bridge to settling tanks and then to “drys” near Shaugh Bridge. We saw the remains of the “drys” in the National Trust Car Park. In the woods we found the settling tanks and for much of the rest of the walk we followed the ceramic pipeline that carried the crude kaolin suspension. How different this area must have been in the heyday of the granite and china clay industries.

Ceramic pipeline, Plym Valley, Dartmoor

Ceramic pipeline

We continued through woodland for a mile or more but were always conscious of the river not far below on our left; its presence reassured us that we were following the correct path. At this time of year, the landscape was mostly green so it was a surprise to come across a clutch of Rowan Trees. Their shocking orange berries will provide welcome food for hungry birds in a few weeks’ time. According to Richard Mabey, the berries, mixed with a few crab-apples, can also be used to make a “sharp, marmaladish jelly, traditionally served with game and lamb”.


Rowan Tree

Nearby, where springs wet the ground, we found the small purple flowers of Devil’s Bit Scabious. Devil’s Bit refers, in folk tales, to the short black root, bitten off by the Devil angered by the plant’s ability to treat scabies. This seemed appropriate as across the river valley were the Dewerstone Crags or Devil’s Rocks, beloved of climbers; Dewer is the ancient Celtic name for the Devil.

Devil's Bit Scabious, Dartmoor, Devon

Devil’s Bit Scabious

Dewerstone Crags, Dartmoor

Dewerstone Crags

Further on, the path dropped down to meet the fast flowing river, a perfect place for Dippers. On cue, one of the plump, chocolate-brown birds was there, standing on a rock, bobbing up and down, proudly displaying his white waistcoat while the water flowed swiftly past. We watched until the Dipper decided to leave and then we walked the short distance back to the car.

Dipper on the River Plym


This walk comes from “Dartmoor, Great short walks for all the family”, by Sue Viccars, Crimson Publishing, 2009.

Thanks go to Hazel Strange for the lovely photos.

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She laments, sir,….. her husband goes this morning a-birding

The book stall consisted of at least six large tables covered with all kinds and all sizes of books. Judging from the number of people milling around the stall, there was quality here although the prices (50p for paperbacks and £1 for hardbacks – with reductions for volume!) might have had a hand in this.

We were at the Church Fete in the West Dorset village of Burton Bradstock, about a mile from the Lyme Bay coast. This is a traditional village fete, held in the walled garden of the rectory. There was a large bric a brac stall, a bottle tombola, several children’s games; you could also play “splat the rat” and indulge in “pig racing”, although no animals were actually involved. The St Swithun’s Band (the Brass Band from the nearby town of Bridport) was on hand to entertain and there was a Punch and Judy show given by Professor Pete Milson; apparently all Punch and Judy shows are lead by a Professor (but those who are academics knew that anyway!). The fete is one of the high spots of the local calendar and was very busy on this sunny, warm, early August afternoon.

When we arrived, my daughter headed straight for the book stall and I followed her. She was after classic novels and I was just browsing. I looked at a few books in a desultory manner until I discovered three nature books, one on flowers and two on birds. I have always been a bit of a sucker for reference books and I thought these might be good additions to my collection. To be honest, I didn’t examine the books very carefully but at £2 for the three it seemed like a good deal. My daughter found a couple of large history books and was well pleased.

Later on, I had a better look at the books and was pleasantly surprised. The oldest of the three, dating from 1956, was “A Field Guide to the Birds of Britain and Europe” by Peterson, Mountfort and Hollom. This is a pocket-sized catalogue of all the birds you might see in these regions with hints for identification. For each species there is a short description, a distribution map and a colour illustration. Julian Huxley, writing in the Introduction, tells us that that this was the first book describing all the birds in Europe. To me, what is interesting about this book is that it describes the birds as they were half a century ago, but more about that later.

I also particularly liked the dedication at the front of the book:


She laments, sir,…..her husband goes this morning a-birding
Shakespeare, – Merry Wives of Windsor”

The second bird book dated from 1970. It was the “Collins Guide to Birdwatching” by Richard Fitter. This is very much a practical guide to watching the birds of Britain with very helpful tips on how to identify species based on visual and aural clues. I like his down to earth style which includes statements such as “we are back in the realms of the small brown bird”, summing up my own feelings about bird identification. The text is much more helpful than the illustrations which are black and white photos and line drawings.

The third book, dating from 1974, was “Wild Flowers of Britain and Northern Europe” and was also by Richard Fitter although his son Alastair shared authorship and there are lovely illustrations based on paintings by Marjorie Blamey. There is an extensive practical guide to identification at the beginning of the book and, in my opinion, the illustrations of the flowers are more helpful than any I have encountered in other books.

It seems like quite a coincidence that two of the books I chose were by Richard Fitter, so who was he? He was a British naturalist heavily involved in nature conservation. He wrote many guides for amateur naturalists and these were immensely popular, selling in huge numbers. In his books, Fitter goes out of his way to make field identification of species, both flowers and birds, easier so it’s no surprise that his books were so popular. His son, Alastair is Professor of Biology at York and a Fellow of the Royal Society.

So, I was pretty lucky with these three books and they will be very useful additions to my collection. As I have written before, I am no bird expert. I am interested in the wildlife around me but I don’t make systematic observations. On the other hand, the people who compile these bird and flower books are often dedicated and systematic observers.

These apparently simple but systematic observations can have considerable power, as shown by the work of Richard Fitter and his son Alastair. Richard Fitter kept notebooks recording the flowering times of plants around his home in rural Oxfordshire for more than 50 years. When his son analysed this information, he found that the flowering patterns of plants in the four decades between 1950 and 1990 were very similar but that in the 1990s flowering advanced by an average of 4.5 days. The findings were published in Science in 2002 with both father and son as authors and the changes in flowering time were taken to be a strong biological signal of climate change.

It also occurred to me that if I compare the distributions of bird species in the 1956 and 1970 books with the distribution shown in the 2009 Collins Bird Guide, I might get an indication of any changes over a 50 year period. I haven’t done this extensively yet but I had a look at data on the Cirl Bunting, a species now confined in the UK to a coastal strip of Devon between Exeter and Plymouth, as the 2009 book confirms. The Cirl Bunting is a relative of the Yellowhammer and the male is particularly striking with its green and yellow head and chest. In 1956 the bird was found widely in the southern half of England, roughly below a line linking Liverpool and Ipswich. In 1970 the bird was still found quite widely and Fitter refers to seeing the bird in his Oxfordshire garden. The Cirl Bunting suffered a steep decline after the 1970s and by 1989 it was found only in South Devon with about 100 pairs remaining. The decline was due to changes in farming practice, especially the loss of spring-sown cereal crops and weedy winter stubble. When this was finally realised, changes to farming practice were encouraged through government-funded schemes and the number of Cirl Bunting pairs rose steadily, reaching 862 in 2009. This is a great conservation success story and again emphasises the power of systematic observation.

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