Britain’s patient outlaws

Mark (CC BY 2.0)

Mark (CC BY 2.0)

Medical cannabis is authorized in places as diverse as Canada, Uruguay, Israel and Jamaica. But could legalisation moil in the UK? Katharine Quarmby finds loudly.

On a cold spring evening I entrap a fast train from London to Maidstone in Kent, to qualified Clark French, a young man by multiple sclerosis. I’m joining him and his companions from the United Patients Alliance (UPA) without ceasing a road tour of the UK. The form into ~s French founded last year has the same, on the face of it, elementary mission: the legalisation of medical cannabis in the UK.

I arrive a insignificant early at the old Victorian erection where the UPA is holding its concourse. French arrives five minutes later, smiling and leaning on a stick, and we ~ on inside. While Alex, another activist, fires up the supper urn, French explains that he has in like manner been firing up, discreetly, nearby. He tells me that the agony, tremors and spasms he experiences from his multiple sclerosis can be controlled with cannabis. Without it, he says, his strength to get out of bed in the mornings, hindrance alone do things like speak at meetings, would be greatly reduced.

Although many UPA members live with painful conditions such as arthritis, multiple sclerosis and Crohn’s ailment, they are campaigning hard on this unwedded issue, eschewing the wider issue of wholesale legalisation. In his oral communication to the meeting, French stresses that tongue could help shift public perception – that “patients” should speak about “medicating” and refer to cannabis being of the cl~s who a “medicine” rather than in the same manner with a recreational “drug”. “Multiple sclerosis took to such a degree much from me,” says French. “But allowing that prohibition wasn’t there, I could require my life back… we wholly deserve it. That’s my motivation.”

But it’s not that easy. Whenever French “medicates”, he has to stronghold an eye out for police officers. He, and other medicinal cannabis users, have made themselves outlaws, ~ward one charge only.

It wasn’t evermore like this. British physicians prescribed cannabis as antidote to medical purposes as early as the 1840s, posterior Professor William O’Shaughnessy, an Irish cure, first noted its uses in India in the 1830s. The drug was included in both the British and American pharmacopeias from the 1860s onwards. But things changed. During the 1920s, meaning panic about the drug increased and, aye since, the concern about so-called “reefer madness” has in no degree fully been allayed. Cannabis was eventually outlawed ~ the sake of medical use when the UK Parliament passed the Misuse of Drugs Act in 1971, a firmness that activists refer to as “prohibition”.

Telling the lie of cannabis and the hope it may grasp for sick people is not at rest, not least because of the overlap through its role as a popular recreational mix with ~s. What seems, therefore, like a natural mission – to legalise its conversion to an act for medical purposes – is whole but that.

• • •

Mosaic view: Have you have ever felt concerned all over your use of cannabis for curative condition(s)?

Respondent: I never felt concerned reject when I was going to amass from my dealer. I’m a 64-year-thoughtful great grandmother!

There is one mould of legal licensed medical cannabis in the UK: Sativex. It’s the world’s in the ~ place plant-based cannabis medicine, launched through British company GW Pharmaceuticals in June 2010. Derived from extracts from Cannabis sativa, it contains pressingly equal amounts of two cannabinoids: THC (delta-9-tetrahydrocannabinol) and CBD (cannabidiol). It has been licensed in the UK according to treating spasticity-related symptoms in patients with multiple sclerosis if other treatments are not potent. It has been approved for use in 27 countries.

Sativex likely wouldn’t continue without Elizabeth Brice, a medical journalist who raise that smoking Cannabis sativa relieved the symptoms of her multiple sclerosis in great part better than the first synthetic cannabinoid, nabilone, did as antidote to other patients. Inspired by activism in the USA, she put up a UK branch of Alliance with respect to Cancer Therapeutics in 1992 and she worked with the Multiple Sclerosis Society to lobby in spite of more research and access to cannabis-based physic.

One of the earliest American pioneers in the medical cannabis field, Alice O’Leary-Randall, pays tax to Brice in a Skype meeting from her Florida home: “Liz gave the beyond all others years of her life to increase this established. Such valiant tales should not have ~ing forgotten. I remember seeing her walk on the ground this train platform in London. Her spasticity was acquisition the better of her, she had pair young boys, she was juggling in like manner many things and I was overwhelmed by her courage. Her passion was likewise strong.”

Brice and other activists challenged the drug’s pariah status, leading two delegations to the Department of Health and the Home Office. Crucially, Brice besides lobbied the Home Office to bestow British pharmaceutical entrepreneur Geoffrey Guy a licence to pursue cannabis for research purposes. He and his founding associate, Brian Whittle, named their small biotech corporation GW Pharmaceuticals. Guy wanted to, during the time that he put it then, “bottle the substance of cannabis”. Today, the company continues to advance in successive cannabis-derived products aimed at treating provisions including brain cancer, epilepsy, inflammatory bowel ailment and diabetes.

Cannabis cultivation began in July 1998 and clinical trials were carried exhausted with patients with multiple sclerosis. Patients took the cannabis-based branch orally, which meant that it would be absorbed quickly by the body and allowed patients to superintend their dose. Knowing how to administer cannabis, which is neither water-soluble nor injectable, had evermore been dogged by difficulty. So this newly come delivery system – which also lacked the liable disadvantages of smoking – was explanation to the success of Sativex.

Brice died in 2011, a year ~wards Sativex was licensed in the UK. But her devise is not what it could exist . The National Institute for Health and Care Excellence issued guidelines in opposition to English primary and secondary care recent in 2014, saying that the value of Sativex was too high and that of recent origin NHS patients would have to pay themselves or forgo it. The Scottish Medicines Consortium can’t commend Sativex unless a submission is made ~ dint of. Bayer, which holds the UK marketing rights. Only the NHS in Wales has approved the medicine on prescription, for patients with multiple sclerosis who require spasms that have not responded to other drug.

The Multiple Sclerosis Society found that 2 through cent of people with multiple sclerosis surveyed in successi~ social media were using Sativex (of whom 16 for cent said they had paid beneficial to it rather than getting it without ceasing prescription). Most patients in England wish have to go without, pay because of it privately or go to the horrible market to ease their symptoms. (British patients through other conditions that could be treated legally with cannabis abroad say that they receive been turned into reluctant criminals.)

While Brice’s drudge nearly 20 years ago helped to kick begin the door to British patients hoping to help from medical cannabis, it has after been slammed shut in their faces.

Q: Is in that place is a specific reason that you haven’t used cannabis conducive to your medical condition(s)?

A: I wouldn’t wish for to break the law or take a drug that hasn’t been approved ~ dint of. the medical profession. Also have couple teenage children and think that bringing unlicensed drugs into my home would bestow the wrong message to them.

Sativex is regular one option for medical cannabis. There are other pharmaceutical products in the pipeline. Some are based in c~tinuance single chemicals found in cannabis, so as cannabidiol (CBD), others include a alliance. And, of course, there’s the total cannabis plant itself.

“Cannabis is like a physic cabinet,” says Roger Pertwee, who was subservient in some of the early cannabis trials since multiple sclerosis. “It has a lot of compounds in it that are fresh and unique to cannabis. We be in actual possession of discovered 104 so far, but there are others. There are many possible uses that we have to investigate.”

Pertwee is Professor of Neuropharmacology at the University of Aberdeen and besides GW’s Director of Pharmacology (some of his research at the literary institution is funded by the company). His act, alongside that of other researchers including Raphael Mechoulam and Vincenzo Di Marzo, is auxiliary in our understanding of the endocannabinoid plan, a network of lipids and receptors involved in a broad array of bodily processes, including hunger, memory, pain and mood.

We bring forth two types of cannabinoid receptor: CB1, what one. is mostly found in the brain and spinal small rope, and CB2, which is found mightily on cells in the immune regularity. These receptors are activated by cannabinoids made ~ means of the body (endocannabinoids) as well while synthetic cannabinoids and those present in plants.

Where should of the healing art research focus its efforts exploring medical cannabis? Many prominent researchers, including Pertwee, put faith in that the individual components of cannabis are in greater numbers effective than using the whole found. Focusing on components would also preclude the need for a patient to draw into the mouth and puff out ~ from .

Areas of interest to researchers transversely the world include the possible curative use of THC (the main psychoactive component of cannabis), CBD and other cannabinoids to entertain autoimmune diseases, diabetes, cancer, inflammation, seizures and on a level psychiatric disorders, such as schizophrenia.

At the sanatory school at St George’s, University of London, Dr Wai Liu and his team wish shown that cannabinoids target the signalling pathways that are mutated in cancer cells, that, effectively, tell cells to keep augmenting. THC and CBD can turn these signals along, which may reverse the process of cancer in the cells. The compounds also enhance the action of radiotherapy.

But Liu, overmuch, is sceptical of a whole-fix approach. “We have an striking chance to use a drug derived from the cannabis engender which seems to be anti-cancerous. Let’s scrutiny it, and combine it with other cancer drugs. Let’s not destruction time.

“If you truly give credit to that anti-cancer is the evidence, don’t talk about cannabis ~ one more, in the same way that we don’t discourse about white willow any more for we have aspirin… We don’t want to be hijacked by other motives, like whether or not to legalise cannabis.”

The obviously encouraging results of this kind of be in action have led some patients to bribe cannabis oil online, which is unlawful in the UK. Liu is concerned that patients could exist self-medicating with oil that could have existence contaminated. Another problem, he says, is that other chemicals in the limits of cannabis (minor cannabinoids) could actually oppose the beneficial effects of THC and CBD. He is things being so asking the many medical cannabis users who email him if he can collect their data, for example a potential precursor to a full clinical trial. “We need to take the drugs being sold on the internet,” he says.

These inconsiderable cannabinoids could be helpful too. Pertwee explains: “We were looking at the recital of tincture of cannabis in the past time. We found it contains tetrahydrocannabivarin (THCV)”. The researchers require since found that THCV blocks the CB1 receptor goal partially activates the CB2 receptor. “This efficacy be good for treating stroke and it strength be good for drug dependence,” he says. Other in posse uses are being investigated, including on this account that Parkinson’s and schizophrenia.

But it’s low early days. While some cannabis enthusiasts beware it as a panacea – especially appealing while so many conditions aren’t well treated ~ means of other drugs – as yet, manifest across the board just isn’t in that place.

In summer 2015, a review of the effectiveness of medical cannabis for a reckon of conditions was published. Examining 28 databases, the authors plant moderate evidence that medical cannabis may hinder with spasticity in multiple sclerosis and by neuropathic and chronic pain. But make manifest for other conditions was weaker.

One greater charity, Cancer Research UK, has faced a singly prominent backlash after voicing caution on the eve cannabis. Its Science Communications Manager, Dr Kat Arney, showed me her bulging folder of exploration papers about cannabis, embellished with a sticker of Bob Marley. “Cannabinoids are positively interesting molecules with potential for human freedom from disease,” she says. “I know fully the literature regularly. Nothing tells me that cannabis is a reparative for cancer.”

This cautious stance has led to the fellow-feeling getting flamed on social media. Arney wants state studies to be gathered, saying that the regular course cannabis in its whole-plant fashion is discussed by the online common, uncritically, as a cure-all is unhelpful. “At the force it sounds like – for craving of a better word – serpent oil, and that’s how it is marketed.”

• • •

Q: Is in that place is a specific reason that you haven’t used cannabis as antidote to your medical condition(s)?

A: I do not know how to get it. If I did I would certainly accord. it a try as nearly entirely the painkillers I use make me distasteful.

Canada, Uruguay, Israel and Jamaica are among the countries that have ruled cannabis authorized for medical use. Alongside these repose 23 American states and the District of Columbia, five of that, at the time of writing, be seized of gone as far as legalising recreational exercise too.

But what do we mode by medical use? Steve Rolles, from the between nations think-tank Transform, which campaigns with respect to the legal regulation of drugs globally, sets extinguished some of the options: “Do we be without a standardised herbal product like Bedrocan [from specially grown plants], or a tinge like Sativex, or a single-satisfied pharmaceutical product… or a conspiracy of products?

“Would we tolerate people to ‘grow their own’, of the same kind with some jurisdictions do, or be with the understanding by ‘compassion clubs’? Who would arrange this activity?”

The stated purpose of ~ly of the American state laws is based ~ward the Californian law: “to make secure that seriously ill Californians have the ~ful to obtain and use marijuana with respect to medical purposes where that medical exercise is deemed appropriate”. But there is conflict with federal law, under which cannabis is ~y illegal, and models vary widely thwart state lines. Alice O’Leary-Randall says this discrepance has scattered the movement and dubs it “of medicine cannabis by zip code”.

Most of these states insist upon the patient to have some mould of licence to acquire medical cannabis ~-end not all require state residency. Although almost all states have a list of provisions that qualify for medical cannabis, these differ, with some states permitting it since chronic conditions and others only as antidote to specified illnesses such as cancer.

Data collected in some states suggests that many medical users have capacity for cannabis for chronic or severe suffering, a catch-all, rather than notwithstanding the conditions on which the before anything else activists campaigned: glaucoma, AIDS, cancer and multiple sclerosis. Certified users in Arizona, on account of example, are mostly young and male and use the drug for hurt relief.

This, opponents argue, is proof that medical cannabis has become a at the outset step on the road to recreational legalisation, especially than an end in itself. Kevin Sabet, who advised the Obama giving on drug policy, now works in the manner that a consultant with Smart Approaches to Marijuana, one organisation that opposes legalisation. “In the US we are seeing that medical cannabis is being misused to legitimise recreational employment,” he says.

“We understand that the political movement on medicinal marijuana is tied to legalisation… they have rebranded cannabis, from being about 30-year-original stoners to medical use.” Successfully, also: a 2013 Fox News poll rest that 85 per cent of Americans – and 80 per cent of self-identified Republicans – commend of the medical use of cannabis granting that prescribed by a medical doctor. But you don’t level need a doctor in some states, in the same manner with homeopaths and naturopaths can issue licences.

The effect of cannabis allowed varies. Some states allow patients to grow their own. Others accept restrictive medical cannabis agreements, allowing no other than high-CBD strains (for particular conditions such as epilepsy) – so restrictive, in circumstance, that patients argue that they are unworkable. The Drug Enforcement Administration has likewise raided cannabis dispensaries countrywide, saying that they are not correct serving medical users.

“There are sober impediments to medical cannabis use in the compass of our healthcare system,” O’Leary-Randall says. “There is no consistent education of our healthcare professionals about using medical cannabis, or the endocannabinoid order.” She sits on the plank of the American Cannabis Nurses’ Association, that was set up formally in 2012 to accord. nurses advice on how to subsidize patients and dispense safely, without violating founded on law or their licence.

Pharmacists, also, walk a tightrope. Nearly 20 years succeeding the legalisation of medical cannabis, the American Society of Health-System Pharmacists (every official body for the profession) encourages examination into, but not distribution of, therapeutic cannabis, so qualified pharmacists have historically been disinclined to get involved. Recent discussions ~ the agency of the body, however, suggest a softening of relation towards medical cannabis. A new corpse, the National Association of Cannabis Pharmacy, was launched the ~ time year.

O’Leary-Randall wants greater degree of qualified pharmacists to be involved in dispensing cannabis, granting she acknowledges the difficulties: “Cannabis is so unique… It’s rather daunting on the side of elderly people to go into a dispensary and consider at names like Purple Haze and Skunk Weed and pick out what is their medicine. I would passionate affection to see pharmacists more active in this such we can standardise this and engender people more comfortable.”

A Dutch assemblage called Bedrocan is changing things in Europe and more remote afield. The company grows six strains of cannabis with varying cannabinoid content under stringent provisions. They seal it in canisters that are in consequence dispensed by high-street chemists, who be able to give advice to patients.

Bedrocan cannabis is to be turned to account on prescription in Italy, Germany, Finland, the Czech Republic and the Netherlands, but that is expensive in Italy (leading users to ~ round to the black market instead) and toward impossible to obtain in Germany. The company also exports to Canada. In exposition, doctors in other EU countries, apart from the UK, can prescribe Bedrocan for patients, although this is not entirely unmistakable (France and Ireland, too, appear to interdict import).

Dr Stephen Wright, Chief Medical Officer of GW Pharmaceuticals, points audibly that although Bedrocan is prescribed, it has not been formally approved in the same manner with a medicine. “In the EU, Sativex is the alone approved cannabis-based medicine. In more territories, herbal cannabis is available adhering special licence – this is not the like as being an ‘approved’ physic.”

The benefit of the medicines approval rule is, he says, that the sufferer, caregiver and healthcare professional can be certain that a substantial body of independently reviewed philosophical evidence demonstrates the safety, efficacy and sort of the medicine.

Q: Is in that place a specific reason that you haven’t used cannabis beneficial to your medical condition(s)?

A: Concerned that more of the ingredients may do greater degree harm than good ie the psychotropics.

Meanwhile, similar to pockets of legalisation open across the cosmos, UK medical bodies remain cautious over medical cannabis. Although they support the widespread study into the components of cannabis, they require the drug supplied in its alert component parts on the pharmacy shallow, rather than grown in the back garden.

One conception for this is the sidemovables of using the whole plant, even supposing they are hotly debated. Research shows that driving in which case cannabis-impaired (hard to define, bound typically taken to be for couple to ten hours after use) near doubles the risk of a car splinter. Around 10 per cent of cannabis users determine develop dependence, although this is sink than for other legal drugs, like as nicotine and alcohol, with concatenation rates of around 32 per cent and 15 for cent, respectively.

Another concern is encompassing what happens if you start using cannabis at a young date, particularly in terms of cognitive impairment and psychosis, even supposing, again, these relationships are debated.

A newly come risk assessment by German and Canadian researchers concluded that a “limit of exposure” approach to drugs (the rate of the highest level of deaden with narcotics possible with no ill-effects to “estimated human intake”) indicated that highly rectified spirit and tobacco should be regarded to the degree that high-risk, unlike cannabis, which was ranked while low-risk. The researchers caution, however, that these findings relate only to destruction and not other long-term effects such as psychosis.

The average bring to the same ~ of THC in cannabis available in the UK is boil and with it is the dare to undertake of psychosis in users, although cannabis enthusiasts naze out that, historically, there have evermore been high-THC strains available.

Dr Vivienne Nathanson from the British Medical Association (BMA) says that notwithstanding that the BMA believes drug use through se should be medicalised, rather than criminalised, it relics cautious: “For most people the dysphoric personal estate are unhelpful,” she says. “The passage out here is for people with chronic or terminal illnesses that they scarcity pain-free symptom control; they indigence control back over their lives. Giving them of recent origin symptoms does not help.”

The Royal Pharmaceutical Society is in like manner wary about a medical model that gives entranceway to the whole plant. Neal Patel, a pharmacist and its Head of Corporate Communications, explains that the the world has been instrumental in bringing Sativex to the mart. “We start from the vista that we need safe, effective, abstruse-quality medicine for patients. We are massively supportive of the licensing rule in the UK… We transact not want people exposed to greater detriment. Does the drug work? Does it observe something beyond placebo?”

Would the Royal Pharmaceutical Society bread a Bedrocan-type model? “We hoax not believe this should be sold from one side pharmacies,” he says. “Pharmacies are places to advance for health advice, not recreational drugs.” None of the UK eminently-street pharmacies I contacted, nor the supermarkets offering pharmacy services, would comment on whether they would have existence willing to offer medical cannabis in this fashion if legalised.

US drugs consultant Kevin Sabet sums it up: “I like the UK come, with products such as Sativex and scrutiny on the components of marijuana. I don’t like medicinal and recreational issues being mashed together. The medical value is a many question to legalisation.

“I’m not adage there are not genuine patient advocates who straits something for the condition that is infirm them. But if that is the capsule, get them non-smoked experimental drugs from one side their doctors.”

• • •

Q: Have you ever felt concerned about your use of cannabis on the side of medical condition(s)?

A: There is ~t one control over the quality, no assurance of supply and it isn’t lawful.

Because so much about the exercise of medical cannabis in the UK is unascertained, Mosaic carried out a small ~ing of people with long-term deep-seated or life-limiting conditions or impairments (you can see some of the responses of the same kind with section headings throughout this piece).

In every one of, 178 people responded, with more than two times as many women as men. Around 40 per cent of respondents had used cannabis in quest of medical purposes.

Of those who had used it, above half had found that it relieved unhappiness. One-fifth said that cannabis worked more desirable than other drugs they had used, and the like proportion said that cannabis had fewer secteffects. Twelve per cent said it allowed them to secure on with everyday life, and 11 by cent said that it enabled aptitude to motion.

When asked who should have admission to cannabis, a quarter of wholly the respondents said people in indigence of pain relief should; a farther quarter said anyone with a sanatory condition that would respond to cannabis; 13 per cent wanted it limited to nation with terminal and chronic conditions. Just 12 through cent were in favour of legalisation from one side of to the other the board.

The respondents who weren’t publicly using medical cannabis gave a run over of reasons for this, including concerns about the dosage and purity of cannabis and its unwanted espouse a causeeffects. Nearly half of non-users expressed care about cannabis being illegal, as did closely three-quarters of people who had used it during the term of medical reasons.

These fears are not ungrounded. A number of United Patients Alliance members esteem been arrested or faced trial for cannabis-related offences. With ongoing curative conditions for which they use the mix with ~s repeatedly, they are, once identified, sitting targets for law enforcement. Some become repeat offenders, complete with a malefactor record that causes problems with office.

Billy Gartside, who was diagnosed by multiple sclerosis more than 20 years ~ne, spoke about his trial in May 2015. “I desire been acquitted before on the grouts of medical necessity, but I am up in court once more for the same offence. I deem people like me and Clark [French] need to stand up; we have ~t one choice. It’s time the raids stopped… The menace of jail is scary.” He was convicted and, at sentencing in June, admitted a 12-month community order and a four-month ankle game of ~.

Some senior police officers agree, arguing that British deaden with narcotics laws have failed to reduce mix with ~s use and the harms associated through it, and are long due each overhaul. Durham’s Chief Constable, Mike Barton, has called in quest of the decriminalisation of drugs. In July 2015, Ron Hogg, antecedent police officer and now Police and Crime Commissioner in the place of Durham, announced a change in stratagem for his force. He said: “We are not prioritising family who have a small number of cannabis plants with regard to their own use. In low-flat cases we say it is more intimate. see various meanings of good to work with them and enjoin them in a position where they have power to recover.”

Tom Lloyd, the forgoing Chief Constable of Cambridgeshire, takes a like view. “What sense does it show to kick down the door of a individual taking cannabis as the only operative treatment for their multiple sclerosis, conducive to example, to take away their medicine, a few plants, and prosecute them?” he related, at the Home Affairs Select Committee’s eminently-level drugs conference in March 2015.

Medical cannabis had been left right hand the official agenda for the concourse, which took place in the green grounds of Homerton College, Cambridge. However, it kept explosion through, as opponents and proponents of better alluded to it, with anger and rapture. Supporters of the status quo argued that there were far too many speakers in favour of liberalisation. There are few in the world of drug worldly wisdom, I realised that day, who can claim to be neutral voices, uniform when the discussion is simply nearly whether or not cannabis is, or is not, of of medicine benefit.

Professor David Nutt, one of the most famous British drug reformers, was oratory on drugs and social harm. His general contents, that legal drugs such as tobacco and pure spirit are as harmful as drugs such as cannabis, lost him the chairmanship of the Advisory Council in c~tinuance the Misuse of Drugs six years past. In a break, Nutt said that he favours the Californian shape and is already talking to specialist suppliers who could gist cannabis. We discussed how politicised the medicine debate is. Alluding to how cannabis was banned, he declared: “This was the first time that a control had decided to take a remedial agent out of circulation for political reasons.” The civil nature of the debates around cannabis hasn’t changed.

But politicians – and unruffled a sceptical press – have started to examine judicially the plea of those campaigning notwithstanding access to medical cannabis. With a Conservative management of an estate back in power in the UK, notwithstanding that, they have lost ground that they had made, influencing Liberal Democrat and Green politicians who devise not see power any time in a short time.

Q: Why do you use cannabis in opposition to your medical condition(s)?

A: Because at intervals pain is unbearable and you’ll cook anything to stop it.

4/20 – differently known as 20 April – is the be ~d on which cannabis enthusiasts across the earth meet up to celebrate the herb. On Sunday 19th I went prostrate to Hyde Park in London to understand the celebrations and meet up through the United Patients Alliance and other groups. A hardly any thousand enthusiasts had gathered, despite the ponderous policing. Clark French was too misfortune to talk, but Jonathan Liebling, the group’s Political Director, spoke in his seat.

As smoke drifted low across the grass, the dispute of one drug policy analyst I’d oral to came to mind. “Why carry on you think cannabis isn’t legalised?” the analyst asked me, rhetorically, before answering the trial: “Because a bunch of stoners are irksome to do it.” That disgrace – that “stoners” cannot perhaps achieve a change in the science of ~s – is, at long last, falling from home. Change may be a long time arrival, but Britain’s patient outlaws may take history on their side.

This fabrication first appeared on Mosaic and is republished in the present state under a Creative Commons licence.

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