Why a talented researcher – but a naive saleswoman – had to resort to #crowdfunding

I went and wrote, go ahead, launch the campaign – unprepared, at the end of July. That said, we ARE going to succeed in raising the money we so desperately need to make concrete things happen in our lab: registering the very many families who have been willing to participate in this research for years now, and processing their biological samples to discover the answers to those questions that just keep coming.

Why do some children with congenital melanocytic nevi (CMN) die of cancer or brain malfunctions? That’s the big one. Far too many of them – and we as yet have no idea what distinguishes their CMN from the other kids who continue to live with the difficult social stigma of looking sometimes very different. A survey and registry, but above all, the biological specimens and comparing their characteristics to our animal models, will help us understand. Our lab is collecting them, but I need personnel to really make it happen.

Therapies might already be on their way because of recent findings as to what genes can be mutated and in what tissues. However, we still don’t know how these genes work during development or how the hyperactive proteins they encode might be counteracted safely. Our research is designed to answer these questions.

The first genes identified were the same ones often mutated in adult-onset melanoma, only before birth and without sun exposure. CMN kids mostly don’t have melanoma – except for those who then do develop melanoma. A vastly greater proportion than among children without CMN. I am aware of two children in the world fighting their CMN-related melanoma as I write you, and those are just the ones I know. It is heartbreaking.

You would think that governments would recognize the potential impact of rare disease research in a condition affecting kids from birth, for understanding and treating a common adult cancer. It’s exceedingly difficult anywhere in the world, to get so-called public funding for a condition that affects a tiny percentage of the population and their caregivers

Therefore, I turn directly to the public. You. Please back this project. Show the world that the number of people affected with a difficult rare condition should not be part of the cost-benefit analysis for worthwhile research.

Look how beautiful people with CMN are! (If you follow this link, click the little boy on the stairs, for a beautiful photo campaign sponsored by Nevus Outreach, Inc. in the U.S.)

My major motivation – one of those lovely teens with CMN is my daughter. Another motivation – another one of those lovely teens had a piece of her brain removed a few years ago, to control her CMN-related epilepsy by removing the pigmented area. Another motivation – any of those lovely teens sometimes feels uncomfortably different from everyone around her, and that’s outside of spending time in the hospital, which they all have.

Look soon for a video introduction to my research group, and interests, and perhaps some more motivations.

Thank you so much for your interest and support.

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Disturbing the natural order – the case of neonicotinoid insecticides and farmland birds

Apus apus 01.jpg

A swift


One of my favourite nature writers is Mark Cocker who has the ability to capture a scene or an idea in a few hundred words. Despite his immense knowledge he never loses his sense of awe and with clever use of metaphor, his descriptions of nature leap in to life.

Here is Cocker writing about the interdependence of birds and insects:
“…… that vast efflorescence of insect life is integral to spring. After all, those swifts newly screaming over our village and the chorus that greets us at first light are little more than arthropods processed by avian digestive systems”.

Another favourite nature writer, Kenneth Allsop wrote, nearly fifty years ago, also about bird/insect interdependence. He took the example of a pair of dunnocks in the breeding season who consume more than 1000 insects each day just to maintain their chicks. Many of those insects, he pointed out, will be garden pests, “worth bearing in mind when irritated by bird damage to the green peas and apple buds”.

Despite this obvious dependence of bird life on insects, we still dump insecticides on to our gardens, parks and farmland with little real thought about the long term consequences.

One class of insecticide that has recently attracted scrutiny is the neonicotinoids. The neonicotinoids were introduced in the 1990s and are now very widely used to kill insect pests on a broad range of crops. In the UK, for example, a large proportion of the oil seed rape is grown using seed treated with neonicotinoids. One of the advantages of the neonicotinoids is their selectivity for invertebrates; in principle they have low toxicity towards vertebrates. There has, however, been increasing concern about effects of the neonicotinoids on non-target insects such as bees and the accumulation of the chemicals in soil and water courses with more general effects on invertebrates.

New worries about the neonicotinoids surfaced last week in a paper published in Nature by Hallmann and colleagues from Radboud University in the Netherlands. The Dutch group investigated whether these chemicals might be affecting the numbers of farmland birds indirectly by reducing the numbers of insects that these birds depend upon especially in the breeding season.

They took advantage of long-term monitoring schemes in the Netherlands to compare the average concentrations of one neonicotinoid (imidacloprid) in surface water between 2003 and 2009 with bird population trends over the same period. The comparison was made in different regions across the entire country and focussed on 15 species of common farmland bird that depend on invertebrates during the breeding season.

Yellow wagtail.jpg

Yellow wagtail (one of the farmland birds suffering a decline)


The comparison showed that in regions where concentrations of imidacloprid in surface water were higher, population growth rates of these insectivorous birds were lower or negative. Although superficially this suggests that imidacloprid has caused the decline in bird numbers, we first need to rule out alternative explanations for the apparent association.

Hallmann and colleagues consider two possible alternatives: first, the apparent effect of imidacloprid might actually reflect an ongoing decline in bird numbers that predated the introduction of this insecticide; second, the apparent imidacloprid effect might actually reflect changes in land use linked to agricultural intensification. They eliminate both of these alternatives.

Another possible confounding factor that the authors seem to have ignored is the effect of other pesticides. The Netherlands is a very intensively farmed country with more than 60% of land under cultivation. Many different chemicals are used to control pests including imidacloprid. It seems likely that areas with high imidacloprid use will be associated with high usage of other chemicals. Another Dutch group has analysed the large numbers of chemicals present in Dutch agriculture and shown that, in some regions, concentrations of imidacloprid are high enough to kill invertebrates but levels of other chemicals also exceed toxic doses. So, it could be imidacloprid that is leading to the decline in farmland birds or it could be a generally toxic environment. Either way, the conclusion is bleak and ought to make us reflect on the way we are producing our food.

Although the effects of imidacloprid described in this paper are open to interpretation, the evidence against the neonicotinoids continues to accumulate and some authors believe they are having widespread deleterious effects on the natural environment. George Monbiot, writing in the Guardian last week, called for a complete ban on the use of these insecticides.

The Center for Food Safety, a US-based non profit organisation, recently took a different approach to the neonicotinoid problem by asking how much the insecticides actually increase crop yield. Analysing 19 published studies, they found either inconsistent or no evidence that neonicotinoids increase yield. So, astonishingly, dumping neonicotinoids on farm crops has little discernable effect on productivity. Have we all been conned by the agrochemical companies?


[picture credits: “Apus apus 01” by Paweł Kuźniar (Jojo_1, Jojo) – Own work. Licensed under CC BY-SA 3.0 via Wikimedia Commons.

Yellow wagtail” by Andreas TrepteOwn work. Licensed under CC BY-SA 2.5 via Wikimedia Commons.]

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The Flying Squad*

An imposing, white-painted beehive stood in the middle of the room. Emblazoned across the front in large black letters was one word – POLICE.

The police keep bees?

But why?

On a nearby wall was a screen showing a short documentary film: “Policing Genes” by Thomas Thwaites. The film featured police beekeeper, Mark Machan, from the Metropolitan Police Genetic Surveillance Unit. Machan manages 43 beehives around south London and part of Kent. He collects pollen from bees returning to their hives. The pollen is analysed to see if people are growing GM crops and infringing intellectual property; also whether they are cultivating illicit substances. Machan takes advantage of the bees’ “waggle dance” to locate the source of the pollen. Bees returning to the hive perform this dance to communicate the location of rich forage to their nest mates. Machan analyses these waggle dances to infer the location so that officers can be sent to suburban gardens growing unlicensed GM plants. The advantage of using bees is that they can go anywhere, they don’t need a warrant. They save human time and money.

It sounded plausible and I must admit that, for a short time, I believed the story, but this was an art gallery and I should have been more circumspect.

0TC1004_WELLCOME_ 092_fin_RGB_v2_Large.jpg

The poster advertising the Apiculture exhibition


I was visiting the recent exhibition “Apiculture: Bees and the Art of Pollination” at the University of Plymouth which showed how artists have responded to the problems faced by bees. The exhibition was curated by Amy Shelton as part of the Honeyscribe project which explores the relationship between bee health, human health, the environment and the arts. Her exhibition brought together the work of ten internationally known artists many of whom also work with scientists.

Once I realised that I was being taken for a ride, I could see that the police beehive and this film might be warning about of the perils of a culture where overexploitation of wildlife and infringement of personal freedom were commonplace.

I was made to think again, however, when I read a recent paper from the Apiculture Group at Sussex University. Dr Margaret Couvillon and colleagues had been interested to find out whether so-called agri-environment schemes really were effective. Major changes in farming have occurred since the middle of the 20th century leading to the loss of habitat for wildlife and the increased use of chemicals. European Union agri-environment schemes are designed to provide practical support to farmers to protect valuable and threatened landscape and to encourage them to adopt practices that support wildlife. Different levels of “stewardship” exist corresponding to different levels of support for the environment. Payments amounting to £400 million a year are made to farmers in England for these schemes but outcomes are often unclear.

In this new study, Couvillon and colleagues have used foraging honeybees to act as assessors of landscape quality to see if agri-environment schemes actually do deliver.

Honeybees depend for their survival on the availability of abundant forage in the form of flowers so they are continually assessing the “quality” of the surrounding environment. Worker bees returning to the hive perform the “waggle dance” to communicate to their nest mates the location of the most profitable foraging locations. The waggle dance encodes information about the distance and direction of the preferred forage and if this “language” could be decoded then honeybees could be used to monitor the quality of the landscape.

The Sussex group have done just that. By analysing the bees’ waggle dances, they can “eavesdrop” on honeybee workers when they express their foraging preferences for different types of landscape. Three hives situated at the University of Sussex were studied over two flowering seasons. The bees foraged over a mixed landscape consisting of urban land, rural land receiving no environmental support and rural land receiving different levels of agri-environment support. Couvillon and colleagues decoded waggle dances from 5484 worker bees and found considerable variation in foraging preference for different parts of the landscape. Rural land supported by agri-environment schemes was visited more often by the bees whereas urban land, rural land not receiving agri-environment support and, surprisingly, rural land under organic stewardship were visited less often.

The bees expressed their strongest preference for rural land under higher level stewardship including local nature reserves. These schemes provide the greatest support for the environment and may encourage growth of forage-rich wild flowers. Money spent on higher level stewardship schemes and nature reserves may, therefore, be helping to support bees and other important pollinators whose habitat has been degraded by changes in farming practices during the 20th century.

In contrast, the bees expressed their lowest preference for rural land under organic entry level stewardship. Although this scheme does provide support for the environment and the land is farmed using organic principles, the practices used to establish the land may prevent nectar-rich plants from flowering. This unexpected observation should make organic farmers reflect on the methods they are using.

This is a fascinating study illustrating how the language of the honeybee waggle dance is used to communicate information about the health of the surrounding landscape to the hive community. Couvillon and colleagues have shown that by translating the bee language they can also access this information and, potentially, use it as an important tool to inform policy for supporting wildlife.

At the end of the paper, Couvillon and colleagues emphasise how, with their analysis, honeybees can be used to survey landscape health and they can do this more cheaply, more effectively and more quickly than humans could ever do – a surprising echo of the words used by the “police beekeeper”.

*The Flying Squad is a branch of the UK police specialising in the investigation of commercial armed robberies. They were immortalised in the TV series, The Sweeney.

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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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