Wikipedia may not be the best place to start a bibliographical essay; it is unpopular in academic circles due to a lack of citations and references and often unreliable information. However, it does offer a basic overview of many different topics; from people to places, from theories and concepts to events throughout history.  In the Wikipedia article about Wilkie Collins’ The Moonstone, under the heading of ‘Literary significance and criticism’, it says that ‘one of the things that made The Moonstone such a success was its sensationalist depiction of opium addiction’. Although opium use and addiction is a prominent theme throughout the novel, and the novel does come from the ‘sensation’ genre, is the representation of opium addiction itself sensationalist?

Opium has been used in a medicinal context for around 6000 years, and its effects on the mind and body were taken advantage of in Greek, Roman and Arabic medicine (Berridge and Edwards 1981: xviii). Opium can have a euphoric effect, with an effect ‘not exactly equivalent to sedation’, but leading to a ‘tranquil pleasantness’ which ‘can be very positively enjoyable’ (1981: xxi). Following its introduction into Britain, ‘opium was first believed by many to be a medical miracle’ (Landow and Allingham, 2006) and marketed to the masses in various forms; Godfrey’s Cordial, Dalby’s Carminative, McMunn’s Elixir and Batley’s Sedative Solution are examples of just a few medicines containing opium, all sold without any regulation (Hayter 1971: 31). For many years, opium and its derivatives, including the popular laudanum, was enjoyed by the British public; young and old, rich and poor. Far from being a middle class pastime, opium was used in many households as a startlingly normal practise. It was seen as ‘central to medicine, a medicament of surpassing usefulness which undoubtedly found its way into every home’ (Berridge and Edwards 1981: xxv). It was even said that ‘The bulk of the medical evidence goes to support the verdict that it is not more injurious than the moderate use of alcohol, and that even its abusive use is less destructive to the victim and his friends than intemperance’ (Watt 1892).

Despite the fact that many people around Britain used opium regularly for purely medical reasons, historical emphasis has been placed on those who used it recreationally; ‘popular use always attracted most attention’ (Berridge and Edwards 1981: 49). Amongst those who became most famous for their use – and subsequent abuse – of the drug were the Romantic poets and writers. So why is there such a connection between the use of opium and such brilliantly creative minds? There are two main theories on this subject. The first claims that the use of opium can immerse the user into a dream world separate from Earth – ‘as different from this as Mars may be’ (Abrams, 1934: As cited in Hayter 1971: 13). The second, developed by Professor Elizabeth Schneider, aimed to refute this idea, stating that the idea ‘that Kubla Khan could have been composed entirely in a dream under the influence of opium’ (Hayter 1971:13) was a falsehood. This study had the following results:

…the opium habit does not of itself confer either imaginative stimulus or fantastic dreams and visions; all the effects attributed to it are in fact due to the previous mental and emotional make-up of the opium addict.
(1971: 13)

Thomas De Quincey, writer of the infamous Confessions of an English Opium Eater, shared these views, and repeated them often; ‘If a man “whose talk is of oxen” should become an opium-eater, the probability is, that (if he is not too dull to dream at all) – he will dream about oxen’. (1971: 107). On the surface, there does appear to be a correlation between creativity and the use of opium; after all, virtually all of the Romantic poets used it at one time or another. However, on closer inspection this hypothesis has little or no founding; there were an awful lot of people in Britain at that time who used opium medicinally or recreationally; and by no means did all of them become successful writers!

The joy of having discovered a wonder drug continued for many years, with users and doctors alike completely oblivious to the terrible effects addiction to and withdrawal from opium could have. In 1700 Dr John Jones published The Mysteries of Opium Reveal’d, featuring a seemingly endless list of the positive effects opium could have on your health, including such tempting sounding promises as ‘Euphory, or easie undergoing of all Labour…’ (1971: 24). Surprisingly, though, this book also showed that as early as 1700, people were aware of the risks of excessive doses of opium, or sudden withdrawal from it. The general consensus, despite this, however, was that there was not ‘any danger in moderate addiction, or any difficulty in gradual withdrawal.’ (24)

Wilkie Collins is an author who, like many others at this time, began taking opium (in his case, in the form of laudanum) for health troubles, including a rheumatic complaint (1971: 255). In June 1853, Collins’ close friend Charles Dickens wrote to him enquiring after his health; ‘I am very sorry indeed to hear so bad an account of your illness, and had no idea it had been so severe’ (Sayers 1977: 98). Collins’ health continued to be poor; eleven years later in 1864 Collins wrote in a letter to his mother, Harriet, that his rheumatic conditions had developed into a series of problems including ‘gouty irritation’ (Baker and Clarke 1999: 253), digestion problems and headaches (1999: 252).

Collins certainly was an excessive user of opium. Hayter relates a story about Collins’ addiction which has almost become the stuff of urban legends. Following a question about the amount of laudanum consumed by Collins on a daily basis, surgeon Sir William Ferguson replied that ‘this dose of opium, to which Wilkie Collins had habituated himself through long usage, was enough to kill every man seated at the dinner table’ (Bancroft, as cited by Hayter 1971: 256). The fact that Wilkie allowed such matters to be discussed showed that he was not ashamed of his habit; in fact, he was almost boastful of it at times (1971: 257). In 1865, a year after his letter to his mother detailing his still ailing health, it is clear to see that addiction has taken hold of Collins, as he wrote:

Who was the man who invented laudanum? I thank him from the bottom of my heart…I have had six delicious hours of oblivion; I have woken up with my mind composed; I have written a perfect little letter… – and all through the modest little bottle of drops which I see on my bedroom chimneypiece at this moment. Drops, you are darling! If I love nothing else, I love you!
(P. Haining, as cited by Berridge and Edwards 1981: 58)

As his addiction continued and worsened, it seemed to have a detrimental effect on his life and his work. Opium became a more and more prominent theme in his books. In 1862, he published No Name, in which Magdalen Vanstone contemplates her existence, with a bottle of laudanum in her hand should she decide to kill herself. Four years later in 1868, Miss Gwilt in Armadale echoes the very same words recorded by Collins himself; ‘Who was the man who invented laudanum? I thank him from the bottom of my heart, whoever he was’.

Collins’ most famous work in terms of opium use was The Moonstone, which brings me back around to my original question; is it true that the depiction of opium addiction in this novel is sensational? We have already established that the use of opium was common, and addiction to opium was by no means sensational at this time; so the only thing left that could possibly be described as sensational is this specific account of addiction.

The Moonstone’s opium addict, Ezra Jennings, is widely considered to be at least partly autobiographical (Berridge and Edwards, 1981: 58). Jennings is a strange character, with an unusual appearance. He is introduced into the narrative as an assistant to Dr Candy, the family physician. The main way in which Jennings addiction manifests itself is in the form of terrible nightmares. Part of the novel is written in the style of Jennings’ journals, and the following describes a particularly frightening nightmare:

June 16th.—Rose late, after a dreadful night; the vengeance of yesterday’s opium, pursuing me through a series of frightful dreams. At one time I was whirling through empty space with the phantoms of the dead, friends and enemies together. At another, the one beloved face which I shall never see again, rose at my bedside, hideously phosphorescent in the black darkness, and glared and grinned at me. A slight return of the old pain, at the usual time in the early morning, was welcome as a change. It dispelled the visions—and it was bearable because it did that.
(Collins, 1868: 447)

It may be argued that of course such a disturbing, terrifying passage is sensational; but in terms of what an actual addict went through, this experience seems to be quite normal. According to Hayter, it is common for ‘advanced addicts’ to experience horrifying nightmares:

They are often tortured by reptiles and insects – embraced by coiling snakes, trampled on by monsters, crawled on by worms, by ants, by microbes, thrust over precipices by tortoises or fiery dragons. Decaying things, still faintly touched with the likeness of beings once loved, stir beside them in rotting debris; their children, as they kiss them, turn to skeletons. Wandering through huge caves, they are forced to step on rotting corpses, and thousands of faces made of blood-red flames flash up and die out in the darkness.
(1971: 55/56)

This description is surprisingly similar to Collins’ portrayal of Jennings’ nightmares. Collins himself is not documented from having suffered from nightmares, although he did, in the later stages of his addiction, suffer from hallucinations. He believed that people were trying to push him down the stairs, and he spoke of ‘certain vagaries of the optic nerve, which persist in seeing a pattern of their own making’ (1971: 261).

Collins was going through a great many personal problems at the time of writing the novel. In fact, he didn’t write it; he dictated it to a secretary because he was, by this time, in too much pain to write. He was suffering physically from acute pain in his eyes, and mentally from his mother’s illness and inevitable impending death, as well as his own increasingly serious addiction (1971: 261). The Moonstone indeed seems to have some heartbreaking autobiographical elements, including the dream mentioned above. Perhaps the most poignant statement to be found regarding opium in The Moonstone is when Jennings tells Blake that he knows he is going to die following his years of using opium as pain relief:

To that all-potent and all-merciful drug I am indebted for a respite of many years from my sentence of death. But even the virtues of opium have their limit. The progress of the disease has gradually forced me from the use of opium to the abuse of it. I am feeling the penalty at last. My nervous system is shattered; my nights are nights of horror. The end is not far off now.
(Collins, 1868: 430)

There is no doubt that passages such as this one, describing Jennings’ desperation at the progression of his addiction, are at times both harrowing and shocking. However, the autobiographical nature and scientific fact behind the images presented in the novel make it difficult to describe these depictions as ‘sensational’. The terrifying, depressing descriptions of drug addiction and withdrawal may seem like something ‘sensational’ or horrific; but that was the reality for addicts such as Collins.

Works Cited:

• Baker, William, and Clarke, William M., 1999. The letters of Wilkie Collins. Volume 1: 1838-1865, Basingstoke: Macmillan Press Ltd.
• Berridge, Virginia, and Edwards, Griffith, 1981. Opium and the People: Opiate Use in Nineteenth-Century England, Frome: Butler and Tanner Ltd.
• Dr. Watt, 1892. ‘History of Opium, Opium Eating and Smoking (in Anthropological Miscellanea and New Books)’, The Journal of the Anthropological Institute of Great Britain and Ireland, Vol. 21. (1892), pp. 329-332.
• Gregory, E.R., ed and introd. 1977. Wilkie Collins: A Critical and Biographical Study. By Dorothy Sayers. Edited from the Manuscript Humanities Research Center, Austin, Texas. Texas: The Friends of the University of Toledo Libraries.
• Hayter, Alethea, 1971. Opium and the Romantic Imagination (1968), London: Faber and Faber Limited.
• Landow, George P., and Allingham, Philip V., ‘The Medicinal use of Opium in England’  (2 March 2008).
• Stewart, J. I. M., ed. and introd. 1986. The Moonstone, by Wilkie Collins, London: Penguin.
• Wikipedia Article on Wilkie Collins’ The Moonstone;
• Zieger, Susan, ‘The Medical “Discovery” of Addiction’  (2 March 2008).

Someone should write a book about Kratom!

Post from: Synchronium

How Opium Was Really Used (And Abused); The Moonstone, Wilkie Collins and Wikipedia

You Might Be Interested In:

• Kratom: A Brief Overview

Yesterday, Ben Goldacre of BadScience.net published the “missing chapter” from his awe-inspiring book, Bad Science. This book teaches us to use the most foolproof bullshit detector out there (yes, ourselves!) to sift though the mountains of pseudoscientific horse shit in search for the corny nuggets of truth. Ear candles? Homoeopathy?  Fish oil? Gillian McBitchKeith?  Dangers of the MMR vaccine? All horse shit. Seriously, this is one of the best books I’ve read in a long time, and if you don’t already own it, you can buy a copy and get it delivered for little over a fiver!

This new chapter takes on Matthias Rath, a vitamin pill salesman, and reveals him to be one of the biggest bastards out there. You think Big Pharma is the ultimate evil power in the universe? Maybe you should look at the evils of alternative therapy:

The Doctor Will Sue You Now

This chapter did not appear in the original edition of this book, because for fifteen months leading up to September 2008 the vitamin-pill entrepreneur Matthias Rath was suing me personally, and the Guardian, for libel. This strategy brought only mixed success. For all that nutritionists may fantasise in public that any critic is somehow a pawn of big pharma, in private they would do well to remember that, like many my age who work in the public sector, I don’t own a flat. The Guardian generously paid for the lawyers, and in September 2008 Rath dropped his case, which had cost in excess of £500,000 to defend. Rath has paid £220,000 already, and the rest will hopefully follow.  Nobody will ever repay me for the endless meetings, the time off work, or the days spent poring over tables filled with endlessly cross-referenced court documents.

On this last point there is, however, one small consolation, and I will spell it out as a cautionary tale: I now know more about Matthias Rath than almost any other person alive. My notes, references and witness statements, boxed up in the room where I am sitting right now, make a pile as tall as the man himself, and what I will write here is only a tiny fraction of the fuller story that is waiting to be told about him. This chapter, I should also mention, is available free online for anyone who wishes to see it.

Matthias Rath takes us rudely outside the contained, almost academic distance of this book. For the most part we’ve been interested in the intellectual and cultural consequences of bad science, the made-up facts in national newspapers, dubious academic practices in universities, some foolish pill-peddling, and so on. But what happens if we take these sleights of hand, these pill-marketing techniques, and transplant them out of our decadent Western context into a situation where things really matter?

In an ideal world this would be only a thought experiment. AIDS is the opposite of anecdote. Twenty-five million people have died from it already, three million in the last year alone, and 500,000 of those deaths were children. In South Africa it kills 300,000 people every year: that’s eight hundred people every day, or one every two minutes. This one country has 6.3 million people who are HIV positive, including 30 per cent of all pregnant women. There are 1.2 million AIDS orphans under the age of seventeen. Most chillingly of all, this disaster has appeared suddenly, and while we were watching: in 1990, just 1 per cent of adults in South Africa were HIV positive. Ten years later, the figure had risen to 25 per cent.

It’s hard to mount an emotional response to raw numbers, but on one thing I think we would agree. If you were to walk into a situation with that much death, misery and disease, you would be very careful to make sure that you knew what you were talking about. For the reasons you are about to read, I suspect that Matthias Rath missed the mark.

This man, we should be clear, is our responsibility. Born and raised in Germany, Rath was the head of Cardiovascular Research at the Linus Pauling Institute in Palo Alto in California, and even then he had a tendency towards grand gestures, publishing a paper in the Journal of Orthomolecular Medicine in 1992 titled “A Unified Theory of Human Cardiovascular Disease Leading the Way to the Abolition of this Disease as a Cause for Human Mortality”. The unified theory was high-dose vitamins.

He first developed a power base from sales in Europe, selling his pills with tactics that will be very familiar to you from the rest of this book, albeit slightly more aggressive. In the UK, his adverts claimed that “90 per cent of patients receiving chemotherapy for cancer die within months of starting treatment”, and suggested that three million lives could be saved if cancer patients stopped being treated by conventional medicine.  The pharmaceutical industry was deliberately letting people die for financial gain, he explained. Cancer treatments were “poisonous compounds” with “not even one effective treatment”.

The decision to embark on treatment for cancer can be the most difficult that an individual or a family will ever take, representing a close balance between well-documented benefits and equally well-documented side-effects. Adverts like these might play especially strongly on your conscience if your mother has just lost all her hair to chemotherapy, for example, in the hope of staying alive just long enough to see your son speak.

There was some limited regulatory response in Europe, but it was generally as weak as that faced by the other characters in this book. The Advertising Standards Authority criticised one of his adverts in the UK, but that is essentially all they are able to do. Rath was ordered by a Berlin court to stop claiming that his vitamins could cure cancer, or face a €250,000 fine.

But sales were strong, and Matthias Rath still has many supporters in Europe, as you will shortly see. He walked into South Africa with all the acclaim, self-confidence and wealth he had amassed as a successful vitamin-pill entrepreneur in Europe and America, and began to take out full-page adverts in newspapers.

“The answer to the AIDS epidemic is here,” he proclaimed. Anti-retroviral drugs were poisonous, and a conspiracy to kill patients and make money. “Stop AIDS Genocide by the Drugs Cartel” said one headline. “Why should South Africans continue to be poisoned with AZT? There is a natural answer to AIDS.”  The answer came in the form of vitamin pills. “Multivitamin treatment is more effective than any toxic AIDS drug. Multivitamins cut the risk of developing AIDS in half.”

Rath’s company ran clinics reflecting these ideas, and in 2005 he decided to run a trial of his vitamins in a township near Cape Town called Khayelitsha, giving his own formulation, VitaCell, to people with advanced AIDS. In 2008 this trial was declared illegal by the Cape High Court of South Africa. Although Rath says that none of his participants had been on anti-retroviral drugs, some relatives have given statements saying that they were, and were actively told to stop using them.

Tragically, Matthias Rath had taken these ideas to exactly the right place. Thabo Mbeki, the President of South Africa at the time, was well known as an “AIDS dissident”, and to international horror, while people died at the rate of one every two minutes in his country, he gave credence and support to the claims of a small band of campaigners who variously claim that AIDS does not exist, that it is not caused by HIV, that anti-retroviral medication does more harm than good, and so on.

At various times during the peak of the AIDS epidemic in South Africa their government argued that HIV is not the cause of AIDS, and that anti-retroviral drugs are not useful for patients. They refused to roll out proper treatment programmes, they refused to accept free donations of drugs, and they refused to accept grant money from the Global Fund to buy drugs. One study estimates that if the South African national government had used anti-retroviral drugs for prevention and treatment at the same rate as the Western Cape province (which defied national policy on the issue), around 171,000 new HIV infections and 343,000 deaths could have been prevented between 1999 and 2007. Another study estimates that between 2000 and 2005 there were 330,000 unnecessary deaths, 2.2 million person years lost, and 35,000 babies unnecessarily born with HIV because of the failure to implement a cheap and simple mother-to-child-transmission prevention program. Between one and three doses of an ARV drug can reduce transmission dramatically. The cost is negligible. It was not available.

Interestingly, Matthias Rath’s colleague and employee, a South African barrister named Anthony Brink, takes the credit for introducing Thabo Mbeki to many of these ideas. Brink stumbled on the “AIDS dissident” material in the mid-1990s, and after much surfing and reading, became convinced that it must be right. In 1999 he wrote an article about AZT in a Johannesburg newspaper titled “a medicine from hell”. This led to a public exchange with a leading virologist. Brink contacted Mbeki, sending him copies of the debate, and was welcomed as an expert.

This is a chilling testament to the danger of elevating cranks by engaging with them. In his initial letter of motivation for employment to Matthias Rath, Brink described himself as “South Africa’s leading AIDS dissident, best known for my whistle-blowing exposé of the toxicity and inefficacy of AIDS drugs, and for my political activism in this regard, which caused President Mbeki and Health Minister Dr Tshabalala-Msimang to repudiate the drugs in 1999″.

In 2000, the now infamous International AIDS Conference took place in Durban. Mbeki’s presidential advisory panel beforehand was packed with “AIDS dissidents”, including Peter Duesberg and David Rasnick. On the first day, Rasnick suggested that all HIV testing should be banned on principle, and that South Africa should stop screening supplies of blood for HIV. “If I had the power to outlaw the HIV antibody test,” he said, “I would do it across the board.” When African physicians gave testimony about the drastic change AIDS had caused in their clinics and hospitals, Rasnick said he had not seen “any evidence” of an AIDS catastrophe. The media were not allowed in, but one reporter from the Village Voice was present. Peter Duesberg, he said, “gave a presentation so removed from African medical reality that it left several local doctors shaking their heads”. It wasn’t AIDS that was killing babies and children, said the dissidents: it was the anti-retroviral medication.

President Mbeki sent a letter to world leaders comparing the struggle of the “AIDS dissidents” to the struggle against apartheid.  The Washington Post described the reaction at the White House: “So stunned were some officials by the letter’s tone and timing during final preparations for July’s conference in Durban that at least two of them, according to diplomatic sources, felt obliged to check whether it was genuine.  Hundreds of delegates walked out of Mbeki’s address to the conference in disgust, but many more described themselves as dazed and confused. Over 5,000 researchers and activists around the world signed up to the Durban Declaration, a document that specifically addressed and repudiated the claims and concerns–at least the more moderate ones–of the “AIDS dissidents”. Specifically, it addressed the charge that people were simply dying of poverty:

The evidence that AIDS is caused by HIV-1 or HIV-2 is clearcut, exhaustive and unambiguous… As with any other chronic infection, various co-factors play a role in determining the risk of disease. Persons who are malnourished, who already suffer other infections or who are older, tend to be more susceptible to the rapid development of AIDS following HIV infection.  However, none of these factors weaken the scientific evidence that HIV is the sole cause of AIDS… Mother-to-child transmission can be reduced by half or more by short courses of antiviral drugs. What works best in one country may not be appropriate in another. But to tackle the disease, everyone must first understand that HIV is the enemy. Research, not myths, will lead to the development of more effective and cheaper treatments.

It did them no good. Until 2003 the South African government refused, as a matter of principle, to roll out proper antiretroviral medication programmes, and even then the process was half-hearted. This madness was only overturned after a massive campaign by grassroots organisations such as the Treatment Action Campaign, but even after the ANC cabinet voted to allow medication to be given, there was still resistance. In mid-2005, at least 85 per cent of HIV-positive people who needed anti-retroviral drugs were still refused them. That’s around a million people.

This resistance, of course, went deeper than just one man; much of it came from Mbeki’s Health Minister, Manto Tshabalala-Msimang. An ardent critic of medical drugs for HIV, she would cheerfully go on television to talk up their dangers, talk down their benefits, and became irritable and evasive when asked how many patients were receiving effective treatment. She declared in 2005 that she would not be “pressured” into meeting the target of three million patients on anti-retroviral medication, that people had ignored the importance of nutrition, and that she would continue to warn patients of the sideeffects of anti-retrovirals, saying: “We have been vindicated in this regard. We are what we eat.”

It’s an eerily familiar catchphrase. Tshabalala-Msimang has also gone on record to praise the work of Matthias Rath, and refused to investigate his activities. Most joyfully of all, she is a staunch advocate of the kind of weekend glossy-magazine-style nutritionism that will by now be very familiar to you. The remedies she advocates for AIDS are beetroot, garlic, lemons and African potatoes. A fairly typical quote, from the Health Minister in a country where eight hundred people die every day from AIDS, is this: “Raw garlic and a skin of the lemon–not only do they give you a beautiful face and skin but they also protect you from disease.”  South Africa’s stand at the 2006 World AIDS Conference in Toronto was described by delegates as the “salad stall”. It consisted of some garlic, some beetroot, the African potato, and assorted other vegetables. Some boxes of anti-retroviral drugs were added later, but they were reportedly borrowed at the last minute from other conference delegates.

Alternative therapists like to suggest that their treatments and ideas have not been sufficiently researched. As you now know, this is often untrue, and in the case of the Health Minister’s favoured vegetables, research had indeed been done, with results that were far from promising. Interviewed on SABC about this, Tshabalala-Msimang gave the kind of responses you’d expect to hear at any North London dinner-party discussion of alternative therapies.

First she was asked about work from the University of Stellenbosch which suggested that her chosen plant, the African potato, might be actively dangerous for people on AIDS drugs. One study on African potato in HIV had to be terminated prematurely, because the patients who received the plant extract developed severe bone-marrow suppression and a drop in their CD4 cell count–which is a bad thing–after eight weeks. On top of this, when extract from the same vegetable was given to cats with Feline Immunodeficiency Virus, they succumbed to full-blown Feline AIDS faster than their non-treated controls. African potato does not look like a good bet.

Tshabalala-Msimang disagreed: the researchers should go back to the drawing board, and “investigate properly”. Why?  Because HIV-positive people who used African potato had shown improvement, and they had said so themselves. If a person says he or she is feeling better, should this be disputed, she demanded to know, merely because it had not been proved scientifically? “When a person says she or he is feeling better, I must say ‘No, I don’t think you are feeling better? I must rather go and do science on you’?” Asked whether there should be a scientific basis to her views, she replied: “Whose science?”

And there, perhaps, is a clue, if not exoneration. This is a continent that has been brutally exploited by the developed world, first by empire, and then by globalised capital. Conspiracy theories about AIDS and Western medicine are not entirely absurd in this context. The pharmaceutical industry has indeed been caught performing drug trials in Africa which would be impossible anywhere in the developed world. Many find it suspicious that black Africans seem to be the biggest victims of AIDS, and point to the biological warfare programmes set up by the apartheid governments; there have also been suspicions that the scientific discourse of HIV/AIDS might be a device, a Trojan horse for spreading even more exploitative Western political and economic agendas around a problem that is simply one of poverty.

And these are new countries, for which independence and self-rule are recent developments, which are struggling to find their commercial feet and true cultural identity after centuries of colonisation. Traditional medicine represents an important link with an autonomous past; besides which, anti-retroviral medications have been unnecessarily – offensively, absurdly – expensive, and until moves to challenge this became partially successful, many Africans were effectively denied access to medical treatment as a result.

It’s very easy for us to feel smug, and to forget that we all have our own strange cultural idiosyncrasies which prevent us from taking up sensible public-health programmes. For examples, we don’t even have to look as far as MMR. There is a good evidence base, for example, to show that needle-exchange programmes reduce the spread of HIV, but this strategy has been rejected time and again in favour of “Just say no.” Development charities funded by US Christian groups refuse to engage with birth control, and any suggestion of abortion, even in countries where being in control of your own fertility could mean the difference between success and failure in life, is met with a cold, pious stare. These impractical moral principles are so deeply entrenched that Pepfar, the US Presidential Emergency Plan for AIDS Relief, has insisted that every recipient of international aid money must sign a declaration expressly promising not to have any involvement with sex workers.

We mustn’t appear insensitive to the Christian value system, but it seems to me that engaging sex workers is almost the cornerstone of any effective AIDS policy: commercial sex is frequently the “vector of transmission”, and sex workers a very high-risk population; but there are also more subtle issues at stake. If you secure the legal rights of prostitutes to be free from violence and discrimination, you empower them to demand universal condom use, and that way you can prevent HIV from being spread into the whole community. This is where science meets culture. But perhaps even to your own friends and neighbours, in whatever suburban idyll has become your home, the moral principle of abstinence from sex and drugs is more important than people dying of AIDS; and perhaps, then, they are no less irrational than Thabo Mbeki.

So this was the situation into which the vitamin-pill entrepreneur Matthias Rath inserted himself, prominently and expensively, with the wealth he had amassed from Europe and America, exploiting anti-colonial anxieties with no sense of irony, although he was a white man offering pills made in a factory abroad. His adverts and clinics were a tremendous success. He began to tout individual patients as evidence of the benefits that could come from vitamin pills – although in reality some of his most famous success stories have died of AIDS. When asked about the deaths of Rath’s star patients, Health Minister Tshabalala-Msimang replied: “It doesn’t necessarily mean that if I am taking antibiotics and I die, that I died of antibiotics.”

She is not alone: South Africa’s politicians have consistently refused to step in, Rath claims the support of the government, and its most senior figures have refused to distance themselves from his operations or to criticise his activities. Tshabalala-Msimang has gone on the record to state that the Rath Foundation “are not undermining the government’s position. If anything, they are supporting it.”

In 2005, exasperated by government inaction, a group of 199 leading medical practitioners in South Africa signed an open letter to the health authorities of the Western Cape, pleading for action on the Rath Foundation. “Our patients are being inundated with propaganda encouraging them to stop life-saving medicine,” it said. “Many of us have had experiences with HIV infected patients who have had their health compromised by stopping their anti-retrovirals due to the activities of this Foundation.”  Rath’s adverts continue unabated. He even claimed that his activities were endorsed by huge lists of sponsors and affiliates including the World Health Organization, UNICEF and UNAIDS. All have issued statements flatly denouncing his claims and activities. The man certainly has chutzpah.

His adverts are also rich with detailed scientific claims. It would be wrong of us to neglect the science in this story, so we should follow some through, specifically those which focused on a Harvard study in Tanzania. He described this research in full-page advertisements, some of which have appeared in the New York Times and the Herald Tribune. He refers to these paid adverts, I should mention, as if he had received flattering news coverage in the same papers. Anyway, this research showed that multivitamin supplements can be beneficial in a developing world population with AIDS: there’s no problem with that result, and there are plenty of reasons to think that vitamins might have some benefit for a sick and frequently malnourished population.

The researchers enrolled 1,078 HIV-positive pregnant women and randomly assigned them to have either a vitamin supplement or placebo. Notice once again, if you will, that this is another large, well-conducted, publicly funded trial of vitamins, conducted by mainstream scientists, contrary to the claims of nutritionists that such studies do not exist. The women were followed up for several years, and at the end of the study, 25 per cent of those on vitamins were severely ill or dead, compared with 31 per cent of those on placebo. There was also a statistically significant benefit in CD4 cell count (a measure of HIV activity) and viral loads. These results were in no sense dramatic – and they cannot be compared to the demonstrable life-saving benefits of anti-retrovirals – but they did show that improved diet, or cheap generic vitamin pills, could represent a simple and relatively inexpensive way to marginally delay the need to start HIV medication in some patients.

In the hands of Rath, this study became evidence that vitamin pills are superior to medication in the treatment of HIV/AIDS, that  anti-retroviral therapies “severely damage all cells in the body–including white blood cells”, and worse, that they were “thereby not improving but rather worsening immune deficiencies and expanding the AIDS epidemic”. The researchers from the Harvard School of Public Health were so horrified that they put together a press release setting out their support for medication, and stating starkly, with unambiguous clarity, that Matthias Rath had misrepresented their findings.

To outsiders the story is baffling and terrifying. The United Nations has condemned Rath’s adverts as “wrong and misleading”. “This guy is killing people by luring them with unrecognised treatment without any scientific evidence,” said Eric Goemaere, head of Médecins sans Frontières SA, a man who pioneered anti-retroviral therapy in South Africa. Rath sued him.

It’s not just MSF who Rath has gone after: he has also brought time-consuming, expensive, stalled or failed cases against a professor of AIDS research, critics in the media and others.

But his most heinous campaign has been against the Treatment Action Campaign. For many years this has been the key organisation campaigning for access to anti-retroviral medication in South Africa, and it has been fighting a war on four fronts.  Firstly, TAC campaigns against its own government, trying to compel it to roll out treatment programmes for the population. Secondly, it fights against the pharmaceutical industry, which claims that it needs to charge full price for its products in developing countries in order to pay for research and development of new drugs – although, as we shall see, out of its $550 billion global annual revenue, the pharmaceutical industry spends twice as much on promotion and admin as it does on research and development. Thirdly, it is a grassroots organisation, made up largely of black women from townships who do important prevention and treatment-literacy work on the ground, ensuring that people know what is available, and how to protect themselves. Lastly, it fights against people who promote the type of information peddled by Matthias Rath and his ilk.

Rath has taken it upon himself to launch a massive campaign against this group. He distributes advertising material against them, saying “Treatment Action Campaign medicines are killing you” and “Stop AIDS genocide by the drug cartel”, claiming–as you will guess by now–that there is an international conspiracy by pharmaceutical companies intent on prolonging the AIDS crisis in the interests of their own profits by giving medication that makes people worse. TAC must be a part of this, goes the reasoning, because it criticises Matthias Rath. Just like me writing on Patrick Holford or Gillian McKeith, TAC is perfectly in favour of good diet and nutrition. But in Rath’s  promotional literature it is a front for the pharmaceutical industry, a “Trojan horse” and a “running dog”. TAC has made a full disclosure of its funding and activities, showing no such connection: Rath presented no evidence to the contrary, and has even lost a court case over the issue, but will not let it lie. In fact he presents the loss of this court case as if it was a victory.

The founder of TAC is a man called Zackie Achmat, and he is the closest thing I have to a hero. He is South African, and coloured, by the nomenclature of the apartheid system in which he grew up. At the age of fourteen he tried to burn down his school, and you might have done the same in similar circumstances. He has been arrested and imprisoned under South Africa’s violent, brutal white regime, with all that entailed. He is also gay, and HIV-positive, and he refused to take anti-retroviral medication until it was widely available to all on the public health system, even when he was dying of AIDS, even when he was personally implored to save himself by Nelson Mandela, a public supporter of anti-retroviral medication and Achmat’s work.

And now, at last, we come to the lowest point of this whole story, not merely for Matthias Rath’s movement, but for the alternative therapy movement around the world as a whole. In 2007, with a huge public flourish, to great media coverage, Rath’s former employee Anthony Brink filed a formal complaint against Zackie Achmat, the head of the TAC. Bizarrely, he filed this complaint with the International Criminal Court at The Hague, accusing Achmat of genocide for successfully campaigning to get access to HIV drugs for the people of South Africa.

It’s hard to explain just how influential the “AIDS dissidents” are in South Africa. Brink is a barrister, a man with important friends, and his accusations were reported in the national news media –and in some corners of the Western gay press–as a serious news story. I do not believe that any one of those journalists who reported on it can possibly have read Brink’s indictment to the end.

I have.

The first fifty-seven pages present familiar anti-medication and “AIDS-dissident” material. But then, on page fifty-eight, this “indictment” document suddenly deteriorates into something altogether more vicious and unhinged, as Brink sets out what he believes would be an appropriate punishment for Zackie. Because I do not wish to be accused of selective editing, I will now reproduce for you that entire section, unedited, so you can see and feel it for yourself.

The document was described by the Rath Foundation as “entirely valid and long overdue”.

This story isn’t about Matthias Rath, or Anthony Brink, or Zackie Achmat, or even South Africa. It is about the culture of how ideas work, and how that can break down. Doctors criticise other doctors, academics criticise academics, politicians criticise politicians: that’s normal and healthy, it’s how ideas improve. Matthias Rath is an alternative therapist, made in Europe. He is every bit the same as the British operators that we have seen in this book. He is from their world.

Despite the extremes of this case, not one single alternative therapist or nutritionist, anywhere in the world, has stood up to criticise any single aspect of the activities of Matthias Rath and his colleagues. In fact, far from it: he continues to be fêted to this day. I have sat in true astonishment and watched leading figures of the UK’s alternative therapy movement applaud  Matthias Rath at a public lecture (I have it on video, just in case there’s any doubt). Natural health organisations continue to defend Rath. Homeopaths’ mailouts continue to promote his work. The British Association of Nutritional Therapists has been invited to comment by bloggers, but declined. Most, when challenged, will dissemble.”Oh,” they say, “I don’t really know much about it.”  Not one person will step forward and dissent.

The alternative therapy movement as a whole has demonstrated itself to be so dangerously, systemically incapable of critical self-appraisal that it cannot step up even in a case like that of Rath: in that count I include tens of thousands of practitioners, writers, administrators and more. This is how ideas go badly wrong. In the conclusion to this book, written before I was able to include this chapter, I will argue that the biggest dangers posed by the material we have covered are cultural and intellectual.

I may be mistaken.

If you liked that, buy the book! I swear you won’t be able to put it down. You can find more for free at BadScience.net, including Ben’s column in The Guardian of the same name.

Post from: Synchronium

Matthias Rath’s Bad Science Finally Catches Up With Him

You Might Be Interested In:

• 5 Books That Really Will Expand Your Mind!
• Sam Harris, Religion & Drugs

The following passage is taken from Sam Harris’s book, The End Of Faith, and talks about religion’s role in keeping drugs illegal:

The War on Sin

In the United States, and in much of the rest of the world, it is currently illegal to seek certain experiences of pleasure. Seek pleasure by a forbidden means, even in the privacy of your own home, and men with guns may kick in the door and carry you away to prison for it. One of the most surprising things about this situation is how unsurprising most of us find it. As in most dreams, the very faculty of reason that would otherwise notice the strangeness of these events seems to have succumbed to sleep.

Behaviors like drug use, prostitution, sodomy, and the viewing of obscene materials have been categorized as “victimless crimes.” Of course, society is the tangible victim of almost everything human beings do—from making noise to manufacturing chemical waste— but we have not made it a crime to do such things within certain limits. Setting these limits is invariably a matter of assessing risk. One could argue that it is, at the very least, conceivable that certain activities engaged in private, like the viewing of sexually violent pornography, might incline some people to commit genuine crimes against others. There is a tension, therefore, between private freedom and public risk. If there were a drug, or a book, or a film, or a sexual position that led 90 percent of its users to rush into the street and begin killing people at random, concerns over private pleasure would surely yield to those of public safety. We can also stipulate that no one is eager to see generations of children raised on a steady diet of methamphetamine and Marquis de Sade. Society as a whole has an interest in how its children develop, and the private behavior of parents, along with the contents of our media, clearly play a role in this. But we must ask ourselves, why would anyone want to punish people for engaging in behavior that brings no significant risk of harm to anyone? Indeed, what is startling about the notion of a victimless crime is that even when the behavior in question is genuinely victimless, its criminality is still affirmed by those who are eager to punish it. It is in such cases that the true genius lurking behind many of our laws stands revealed. The idea of a victimless crime is nothing more than a judicial reprise of the Christian notion of sin.

It is no accident that people of faith often want to curtail the private freedoms of others. This impulse has less to do with the history of religion and more to do with its logic, because the very idea of privacy is incompatible with the existence of God. If God sees and knows all things, and remains so provincial a creature as to be scandalized by certain sexual behaviors or states of the brain, then what people do in the privacy of their own homes, though it may not have the slightest implication for their behavior in public, will still be a matter of public concern for people of faith.

A variety of religious notions of wrongdoing can be seen converging here—concerns over nonprocreative sexuality and idolatry especially—and these seem to have given many of us the sense that it is ethical to punish people, often severely, for engaging in private behavior that harms no one. Like most costly examples of irrationality, in which human happiness has been blindly subverted for generations, the role of religion here is both explicit and foundational. To see that our laws against “vice” have actually nothing to do with keeping people from coming to physical or psychological harm, and everything to do with not angering God, we need only consider that oral or anal sex between consenting adults remains a criminal offence in thirteen states. Four of the states (Texas, Kansas, Oklahoma, and Missouri) prohibit these acts between same-sex couples and, therefore, effectively prohibit homosexuality. The other nine ban consensual sodomy for everyone (these places of equity are Alabama, Florida, Idaho, Louisiana, Mississippi, North Carolina, South Carolina, Utah, and Virginia). One does not have to be a demographer to grasp that the impulse to prosecute consenting adults for nonprocreative sexual behavior will correlate rather strongly with religious faith.

Jesus once got 5000 people totally baked with only an eighth of weed

The influence of faith on our criminal laws comes at a remarkable price. Consider the case of drugs. As it happens, there are many substances—many of them naturally occurring—the consumption of which leads to transient states of inordinate pleasure. Occasionally, it is true, they lead to transient states of misery as well, but there is no doubt that pleasure is the norm, otherwise human beings would not have felt the continual desire to take such substances for millennia. Of course, pleasure is precisely the problem with these substances, since pleasure and piety have always had an uneasy relationship.

When one looks at our drug laws—indeed, at our vice laws altogether—the only organizing principle that appears to make sense of them is that anything which might radically eclipse prayer or procreative sexuality as a source of pleasure has been outlawed. In particular, any drug (LSD, mescaline, psilocybin, DMT, MDMA, marijuana, etc.) to which spiritual or religious significance has been ascribed by its users has been prohibited. Concerns about the health of our citizens, or about their productivity, are red herrings in this debate, as the legality of alcohol and cigarettes attests.

The fact that people are being prosecuted and imprisoned for using marijuana, while alcohol remains a staple commodity, is surely the reductio ad absurdum of any notion that our drug laws are designed to keep people from harming themselves or others. Alcohol is by any measure the more dangerous substance. It has no approved medical use, and its lethal dose is rather easily achieved. Its role in causing automobile accidents is beyond dispute. The manner in which alcohol relieves people of their inhibitions contributes to human violence, personal injury, unplanned pregnancy, and the spread of sexual disease. Alcohol is also well known to be addictive. When consumed in large quantities over many years, it can lead to devastating neurological impairments, to cirrhosis of the liver, and to death. In the United States alone, more than 100,000 people annually die from its use. It is also more toxic to a developing fetus than any other drug of abuse. (Indeed, “crack babies” appear to have been really suffering from fetal-alcohol syndrome.) None of these charges can be leveled at marijuana. As a drug, marijuana is nearly unique in having several medical applications and no known lethal dosage. While adverse reactions to drugs like aspirin and ibuprofen account for an estimated 7,600 deaths (and 76,000 hospitalizations) each year in the United States alone, marijuana kills no one. Its role as a “gateway drug” now seems less plausible than ever (and it was never plausible). In fact, nearly everything human beings do—driving cars, flying planes, hitting golf balls—is more dangerous than smoking marijuana in the privacy of one’s own home. Anyone who would seriously attempt to argue that marijuana is worthy of prohibition because of the risk it poses to human beings will find that the powers of the human brain are simply insufficient for the job.

And yet, we are so far from the shady groves of reason now that people are still receiving life sentences without the possibility of parole for growing, selling, possessing, or buying what is, in fact, a naturally occurring plant. Cancer patients and paraplegics have been sentenced to decades in prison for marijuana possession. Owners of garden-supply stores have received similar sentences because some of their customers were caught growing marijuana. What explains this astonishing wastage of human life and material resources? The only explanation is that our discourse on this subject has never been obliged to function within the bounds of rationality. Under our current laws, it is safe to say, if a drug were invented that posed no risk of physical harm or addiction to its users but produced a brief feeling of spiritual bliss and epiphany in 100 percent of those who tried it, this drug would be illegal, and people would be punished mercilessly for its use. Only anxiety about the biblical crime of idolatry would appear to make sense of this retributive impulse. Because we are a people of faith, taught to concern ourselves with the sinfulness of our neighbors, we have grown tolerant of irrational uses of state power.

Our prohibition of certain substances has led thousands of otherwise productive and law-abiding men and women to be locked away for decades at a stretch, sometimes for life. Their children have become wards of the state. As if such cascading horror were not disturbing enough, violent criminals—murders, rapists, and child molesters—are regularly paroled to make room for them. Here we appear to have overstepped the banality of evil and plunged to the absurdity at its depths.

The consequences of our irrationality on this front are so egregious that they bear closer examination. Each year, over 1.5 million men and women are arrested in the United States because of our drug laws. At this moment, somewhere on the order of 400,000 men and women languish in U.S. prisons for nonviolent drug offences. One million others are currently on probation. More people are imprisoned for nonviolent drug offences in the United States than are incarcerated, for any reason, in all of Western Europe (which has a larger population). The cost of these efforts, at the federal level alone, is nearly $20 billion dollars annually. The total cost of our drug laws—when one factors in the expense to state and local governments and the tax revenue lost by our failure to regulate the sale of drugs—could easily be in excess of $100 billion dollars each year. Our war on drugs consumes an estimated 50 percent of the trial time of our courts and the full-time energies of over 400,000 police officers. These are resources that might otherwise be used to fight violent crime and terrorism.

In historical terms, there was every reason to expect that such a policy of prohibition would fail. It is well known, for instance, that the experiment with the prohibition of alcohol in the United States did little more than precipitate a terrible comedy of increased drinking, organized crime, and police corruption. What is not generally remembered is that Prohibition was an explicitly religious exercise, being the joint product of the Woman’s Christian Temperance Union and the pious lobbying of certain Protestant missionary societies. The problem with the prohibition of any desirable commodity is money. The United Nations values the drug trade at $400 billion a year. This exceeds the annual budget for the U.S. Department of Defense. If this figure is correct, the trade in illegal drugs constitutes 8 percent of all international commerce (while the sale of textiles makes up 7.5 percent and motor vehicles just 5.3 percent). And yet, prohibition itself is what makes the manufacture and sale of drugs so extraordinarily profitable. Those who earn their living in this way enjoy a 5,000 to 20,000 percent return on their investment, tax-free. Every relevant indicator of the drug trade—rates of drug use and interdiction, estimates of production, the purity of drugs on the street, etc.—shows that the government can do nothing to stop it as long as such profits exist (indeed, these profits are highly corrupting of law enforcement in any case). The crimes of the addict, to finance the stratospheric cost of his lifestyle, and the crimes of the dealer, to protect both his territory and his goods, are likewise the results of prohibition. A final irony, which seems good enough to be the work of Satan himself, is that the market we have created by our drug laws has become a steady source of revenue for terrorist organizations like Al Qaeda, Islamic Jihad, Hezbollah, Shining Path, and others.

Even if we acknowledge that stopping drug use is a justifiable social goal, how does the financial cost of our war on drugs appear in light of the other challenges we face? Consider that it would require only a onetime expenditure of $2 billion to secure our commercial seaports against smuggled nuclear weapons. At present we have allocated a mere $93 million for this purpose. How will our prohibition of marijuana use look (this comes at a cost of $4 billion annually) if a new sun ever dawns over the port of Los Angeles? Or consider that the U.S. government can afford to spend only $2.3 billion each year on the reconstruction of Afghanistan. The Taliban and Al Qaeda are now regrouping. Warlords rule the countryside beyond the city limits of Kabul. Which is more important to us, reclaiming this part of the world for the forces of civilization or keeping cancer patients in Berkeley from relieving their nausea with marijuana? Our present use of government funds suggests an uncanny skewing—we might even say derangement—of our national priorities. Such a bizarre allocation of resources is sure to keep Afghanistan in ruins for many years to come. It will also leave Afghan farmers with no alternative but to grow opium. Happily for them, our drug laws still render this a highly profitable enterprise.

Anyone who believes that God is watching us from beyond the stars will feel that punishing peaceful men and women for their private pleasure is perfectly reasonable. We are now in the twenty-first century. Perhaps we should have better reasons for depriving our neighbors of their liberty at gunpoint. Given the magnitude of the real problems that confront us-—terrorism, nuclear proliferation, the spread of infectious disease, failing infrastructure, lack of adequate funds for education and health care, etc.—our war on sin is so outrageously unwise as to almost defy rational comment. How have we grown so blind to our deeper interests? And how have we managed to enact such policies with so little substantive debate?

Wise words indeed. Sam Harris is a philosopher, neuroscientist and the kind of atheist who takes no shit from anyone. The rest of his book tackles the irrationality of belief, the damage it can do to society and highlights the reasons why religious tolerance is certainly a bad thing. This book should be on everyone’s reading list, but if you’re looking for a more concise attack on irrational belief, I’d also recommend Sam Harris’s other book, Letter To A Christian Nation. Weighing in at just over 100 pages, this is more of an essay than a book, so you’ll finish it in one afternoon.

If you’re one of those rare kinds of people with an attention span longer than 10 minutes, you might also like to watch The Four Horsemen – a discussion between Sam Harris, Richard Dawkins, Daniel Dennet & Christopher Hitchens. It’s two hours long, so you might want to preroll beforehand.

Post from: Synchronium

Sam Harris, Religion & Drugs

You Might Be Interested In:

• 5 Books That Really Will Expand Your Mind!
• Matthias Rath’s Bad Science Finally Catches Up With Him

The use of non-human animals in the drug development process can attract criticism due to the issue of species differences. How significant is this problem and what strategies can be employed to minimise the impact of species differences?

Animal testing is a major tool in the drug development process, required by law before any new drug can enter the market. Animal models are set up to not only test the efficacy of a compound for its intended effect, but also to observe any potential side effects, to calculate a safe dosage for humans and to check for any addiction potential. Although animal testing is a legal requirement, implemented for our own safety, it is still only a model; a substitute for human physiology, whose results could be completely erroneous if they were derived from a poorly planned experiment. Differences between species are always a concern when setting up an appropriate animal model, and a lot of time is spent agonising over them to ensure any results obtained are both accurate and applicable to humans. When it comes to experimental design, species differences can be broadly classified into the following categories: anatomical/physiological differences, differences in metabolism and subsequent toxicity, pharmacological differences and behaviour.

Anatomical/physiological Differences

This is perhaps the most obvious class of species difference. It is no good testing a drug on an animal and looking for effects that are physically impossible for the animal to manifest. Any tests carried out on one species with implications for another must only test parts of the physiology common to both species, or identify an analogous symptom that corresponds to the effect you are looking for.

A prime example of this kind of difference crops up when investigating the emetogenic potential of a drug – unfortunately, evolution has not provided rats with a vomiting reflex, so an different model would have to be devised looking for an alternative behaviour or using another species with a physiology closer to ours.

Metabolism & Toxicity Differences

Different species also metabolise drugs differently – either via different metabolic pathways or with different kinetics. As such, a drug toxic to one species may have little effect on another, which is particularly important when trying to determine the toxicity in humans. A drug’s LD50, the amount required to kill 50% of subjects in a particular sample, is usually given in mg/kg of body mass, scaled up from animal experiments. If a drug’s toxicity or pharmokinetics are only determined from one animal species and extrapolated for the average human, the data would not take into account any differences in metabolism that may be present, resulting in potentially extreme inaccuracies.

For example, dogs should never be given coffee or chocolate, as they are poor metabolisers of theobromine¹, a xanthine alkaloid occurring naturally in both, as well as being a metabolite of caffeine. As little as 50g of chocolate can result in theobromine poisoning for small dogs, while humans can metabolise it fast enough without issue.
Similarly, metabolism of NSAIDs shows a huge variation across different species. The plasma half-life of aspirin ranges from 1 hour in ponies up to 37 hours in cats², due to their poor glucuronidation ability, while dogs are more susceptible to aspirin’s gastrointestinal side effects³.

One final example would be the varying MPTP toxicity between species. MPTP can be formed as an unintended byproduct in the manufacture of MPPP, a synthetic opioid with great potential for abuse. MPTP on its own is not harmful, but MPP+, the natural metabolite of MPTP, is a potent neurotoxin. MPP+ is produced via MonoAmine Oxidase B in neuroglia and the capillary endothelia comprising the blood-brain barrier, and results in rapid-onset Parkinsonian symptoms barely indistinguishable from typical Parkinson’s disease⁴. These symptoms are also reduced by L-DOPA, a drug commonly used in Parkinson’s disease. Rats, however, are almost entirely immune to MPTP toxicity, most likely due to a different level of expression of MAO B⁵. Mice, on the other hand, do produce MPP+, but clear it from their brain in a matter of hours, unlike the primate brain, in which clearance can take days.

Pharmacological Differences

The chemical pathways and their associated protein machinery will not necessarily be structurally identical, or indeed act in the same way. Pathways may be more or less complex, depending on the species, with more or less scope for modulation by other factors. Receptors too may also differ in structure, ligand affinity and the type of G proteins they may couple with. All of these factors may be of huge importance when designing a drug with a particular molecular target in mind.

A few interesting cases have resulted from these types of differences. For a while, Leptin was theorised to suppress hunger, as knockout mice that did not express leptin or its associated receptor got fat. Giving leptin to those that could not express it themselves, but still possessed the appropriate receptor, caused them to lose weight⁶ – a potential gold mine if the results were also applicable to humans. Unfortunately, they were not. Leptin showed little effect in humans, as weight problems tended to concern signal transduction rather than a lack of leptin⁷, in much the same way as insulin-resistant diabetes.

Another, rather more serious example is that of TGN1412, a monoclonal antibody with not only a high affinity for the human CD28 receptor, but a strong agonist ability too. Originally intended to help patients with rheumatoid arthritis and B cell chronic lymphocytic leukaemia, TGN1412 was initially tested on animals and an apparently safe dosage calculated. Of the 6 volunteers hospitalised, each given a dose 500 times smaller than that given to their animal counterparts, 4 developed multiple organ failure as a result of cytokine storm⁸. Hopefully, this example highlights the importance of species difference; that it is a real issue and not just a theoretical concern.

Behavioural Differences

The final category, and perhaps least obvious, is that concerning animal behaviour. Unfortunately for us, animals are not able to clearly express their feelings, so we are left to try and interpret that behaviour, which can be particularly difficult. Humans seem to have an intrinsic penchant for anthropomorphism – we are always unconsciously trying to attribute characteristics that are uniquely human, such as complex emotions or intention, onto animals and even non-living objects. Children are especially guilty of this, smacking a rock, perhaps, as a punishment because it tripped them up. It is only as we grow older and put in a little more thought that we realise that perhaps the rock was not to blame. With animal models, we must also put in that extra thought when it comes to interpreting an animal’s behaviour, instead of opting for the instinctive, humanised interpretation.

Other problems are encountered when we assume a particular behaviour is a result of a particular effect. For example, in the tail flick assay, designed to measure effects on nociception, analgesia is associated with an increased latency in moving the tail away from a heat source. Approving a new drug as an analgesic based on only this interpretation could be disastrous if the increased tail flick latency was instead due to a loss of muscle control or paralysis.

One final thought concerning animal behaviour, is that some behavioural responses may be unique to the species in question. For example, a hedgehog might curl up into a ball as a typical fear response. While this may be easy to interpret, other idiosyncratic responses may not.

Strategies

A number of strategies have been devised for combating the issues species difference brings up, ranging from simple common sense to the rather more complex. An in-depth knowledge of the species under investigation is a good start. Experience and familiarity with a particular species will naturally lead to a better ability to read an animal’s behaviour, just as we become better at reading the people around us the longer we spend in their company. Someone new to animal work will be more likely to anthropomorphise, drawing instead from their experience with other people, whereas someone with ample experience could make a more accurate judgement. Another benefit from experience is that any of the more subtle differences between that species and us is more likely to spring to mind, reducing the risk of something important being overlooked. For example, rat models are a useful tool when studying the intestinal bioavailability of drugs, but are a poor choice when it comes to intestinal metabolism⁹.

Another strategy to reduce the risks imposed by any unknown or overlooked differences, and one that is required by law, is to test on more than one species. Doing so greatly reduces the chances that any observed response is unique to one species in particular, and is therefore likely to be exhibited by humans too.

Although there are an incredible number of individual species, some proteins remain relatively conserved. Working with these specific proteins that share a great deal of similarity between their human counterparts will likely lead to more reliable results. For example, the muscarinic receptor family has remained much the same throughout evolution such that the human and rat receptors share a very similar agonist/antagonist profile¹⁰. It is very likely that something acting on rat muscarinic receptors will elicit the same response in humans, making this an accurate model.

More recently, the latest tools and techniques of the genetic engineer promise to make animal models even more relevant. Genetic manipulation has already delivered knockout animals, not expressing particular genes, and transgenic animals, expressing genes belonging to another species, but in 2008 a chimeric mouse with 90% human hepatocytes (liver cells) was produced¹¹. Until now, the best tool for studying the effects of drugs on the liver would be to use actual human liver (another strategy for overcoming species differences is to use human cells if possible), but the chimeric mouse has already shown great potential. The liver is mainly responsible for the pharmacokinetics of a drug, as it is the primary place that drugs are metabolised, which has subsequent effects on the toxicity and efficacy of that drug. The chimeric mouse has shown a similar pharmacokinetic profile to the human donor, as well as human-specific metabolites not ordinarily found in mice, making this an excellent model with which to study pharmacokinetics and toxicity. This advancement brings with it all the benefits of testing drugs on an actual human target, without any of the ethical considerations raised with human testing.

We humans are an animal species like any other, and we may have our own species-specific responses that are impossible to capture or anticipate with any animal model. It is important to remember that an animal model is just that – a model. Species differences will always be an issue; there are even idiosyncratic reactions to drugs within the same species, such as some humans being allergic to penicillin, so we can never eliminate these differences completely. Increasing research, awareness, criticisms from the animal rights campaigners and new genetic techniques will continue to help us reduce the severity of these issues until they can be reduced no further.

References

1. Kahn CM, editor. The Merck Veterinary Manual. 9th Ed. New Jersey: Merck & Co., Inc; 2008.
2. Boothe DM. The Analgesic, Antipyretic and Anti-inflammatory Drugs. In: Adams HR, editor. Veterinary Pharmacology and Therapeutics. 8th Ed. Iowa: Iwoa University Press; 2001. p. 433-454
3. Crosby JT. Veterinary Questions and Answers – Can you give a dog or cat aspirin? [cited: 2008 Sept 02] About.com: Veterinary Medicine. Available from: http://vetmedicine.about.com/cs/altvetmedgeneral/a/dogcataspirin.htm
4. Langston JW, Ballard P. Parkinsonism induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP): implications for treatment and the pathogenesis of Parkinson’s disease. Can J Neurol Sci. 1984 Feb;11(1 Suppl):160-165.
5. William Langston JW. The Impact of MPTP on Parkinson’s Disease Research: Past, Present, and Future. In: Factor SA, Weiner WJ, editors. Parkinson’s Disease: Diagnosis and Clinical Management, New York: Demos Medical Publishing, 2002. p. 407-436
6. Pelleymounter MA, Cullen MJ, Baker MB, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science. 1995 Jul 28;269(5223):540-543
7. Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996 Feb 1;334(5):292-295
8. Suntharalingam G, Perry MR, Ward S, et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med. 2006 Sep 7;355(10):1018-1028
9. Hurst S, Loi CM, Brodfuehrer J, El-Kattan A. Impact of physiological, physicochemical and biopharmaceutical factors in absorption and metabolism mechanisms on the drug oralbioavailability of rats and humans. Expert Opin Drug Metab Toxicol. 2007 Aug;3(4):469-489
10. Venter JC, Eddy B, Hall LM, Fraser CM. Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with alpha 1-adrenergic receptors. Proc Natl Acad Sci USA. 1984 Jan;81(1):272-276
11. Katoh M, Tateno C, Yoshizato K, Yokoi T. Chimeric mouse with humanized liver. Toxicology. 2008 Apr 3;246(1):9-17

Post from: Synchronium

Animal Testing & Species Differences

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• Living Forever: Is It Really Worth It?

“O brave new world that hath such people in’t!”

Introduction

One way to define ageing is an increased chance of dying as time progresses as a result of cumulative natural changes and degradation of the body. Therefore a cure for ageing wouldn’t simply be a cure for all of the most common diseases associated with old age, such as cancer, heart disease and so on, but rather a cure for the underlying cause of the body being more susceptible to those diseases. Even if we could cure cancer or heart disease, the disease itself may not kill you, but something else would, as the body would still have accumulated years of stress and damage making it increasingly more likely to fail. Instead, a cure for ageing itself would mean prevention (and even reversal) of the ageing process, ensuring a state of perpetual youth for those that partake.

As such, the incredibly complex ethical considerations for such a cure are echoed throughout a number of social and political issues, calling into question the rights of the current generation over future generations, the rights of the individual versus the rights of the society and the purpose of life itself.

Overpopulation

The primary concern that springs to the mind of most people when the topic of curing old age is discussed is overpopulation. Already, the population is growing exponentially, even when the majority of people are dying before they reach 100. If people are living for double that amount of time and reproduction continues at its current rate, surely we will run out of room sooner than if people were dying before 100? It follows then, that we would exhaust that same amount of habitable space even quicker should life expectancy be increased further, to say 500 or in the thousands, provided that the rate of childbirth remained the same.
This idea of cramped living conditions conjures up an image of Victorian style slums or today’s “High Density Living” solution to the same problem in Hong Kong, where the concept of your own space outside has almost disappeared. Not only does that sound uncomfortable with a diminished sense of privacy, but the more people there are in any given area, the more easily and more likely it is that infectious diseases will spread. So how can this problem be resolved? By drastically reducing the birth rate.

Controlling Birth Rate

It would appear that the only option besides killing a large proportion of the population every so often is to place a limit on the rate of child birth for society as a whole. On the surface, this suggests that the generation that decides not to have children so they can extend their own life are making an immoral selfish choice, but let us first take a look at how society handles this issue today.

In 2004, the average number of children per married couple in the UK is approximately 1.8. It is important to realise that this is not a physical limit imposed by the human body, but an amount which is convenient. With the use of birth control and abortions, we can decide when it would be appropriate for us to have a child and how many children we have overall. The point here is that by choosing when to have a child based on factors such as financial stability, we already are being selfish when it comes to reproduction. The world at present is rife with examples of people putting their career (and hence their own satisfaction and financial gain) ahead of their future children, which we do not tend to see a problem with. This hypocrisy extends even further when it comes to the stigma of underage pregnancy – if we as a society should selflessly put our potential offspring before ourselves, surely we should be reproducing as early as possible, no matter what the cost to ourselves? Apparently not. What may seem selfish to some may be perfectly acceptable to others. Unfortunately, it is never clear where the line should be drawn with most ethical dilemmas, and this is no exception.

Selfish or otherwise, there are other pressing matters relating to this kind of population control that must also be discussed. For example, who decides who should reproduce and when? Even China’s notorious “One Child Policy” is not enough to curb population growth. According the British Medical Journal in 2006, “China still has one million more births than deaths every five weeks”, so to prevent overpopulation, the average number of children per family would have to be reduced to far less than one to even keep the population growing at the same rate as China’s is now. Since it’s not possible for every family to give birth to a rather low percentage of one child, the responsibility of deciding who could reproduce and when would have to fall to someone, or some specified group of people, leaving the potential system open to all manner of imperfections. This could include bribery, blackmail, human error and any other form of corruption, which is particularly important with matters as fundamental as this. My lack of faith in humanity being able to think up and implement the perfect system for this situation is still not the most important concern, however.

Assuming that some method of control was necessary and in place, some people would simply not be permitted to reproduce for the interests of society. Not just limited to one child, but not at all. Currently, though, people who decide not to have children, or limit the number they have, retain their right to choose, no matter who may think it immoral; but if society decided the majority wanted to live forever, and the right to reproduce was something worth sacrificing, the choice would then belong to the society and not the individual. Many people see the point of life as having children, and could imagine life as worthless and hollow in hindsight should they not have had their children. The idea of potentially removing what point a lot of people saw in life from those people is one big step up from allowing people to choose when they have children themselves.

Equality & Prejudice

A further ethical topic in need of discussion is just how widespread this cure for ageing would be. The two factors that determine just how far we can expect this cure to reach are choice and availability. The former addresses the question of whether or not the choice would be left up to the individual or decided by the majority.

If it is a majority that decide the fate of quite possibly all of human kind, this decision and all of its implications as outlined here could have a profoundly negative impact upon that minority, however small in number they may be. That minority that would have normally refused treatment if the decision was up to the individual could still be forced not to reproduce by the government for example, as mentioned previously. If the majority voted against it, there would no doubt be ways that particularly rich and powerful people could still acquire the treatment.

If the decision was left up to the individual, some people opting for extended life and others not, it is easy to see how society as we know it may be torn in two in a fashion not too dissimilar to Aldous Huxley’s Brave New World: a completely state-controlled “utopia” on one side, and the “savages” on the other, who opt out of the apparent benefits that such advances may bring. It is not too far fetched to imagine health care for the elderly refused with treatment being the only option, or perhaps a lack of work or housing. We already fear prejudice and ill treatment as a result of genomic sequencing, something that can be kept a secret, but whether or not you’ve taken a cure for ageing could not be hidden. There is an incentive for companies to hire employees who have taken the treatment over people who have not – no pension plans, a reduction of staff turnover, a continued increase in skills without the need to retrain new people. One person doing one job for 150 years will likely be a lot better at that job than someone who has done it for only 50 years, so why wouldn’t companies discriminate against those that opt?

The second factor, availability, needs to be thought about at an international level. Already, the availability of drugs in industrialised nations far exceeds that of developing countries, with over a third of the world’s population having no access to essential drugs. There is no reason to suggest availability of a cure for ageing would be any different, driving the wedge between the rich and poor even further. A possible result could be war for land or resources between both sides of this divide once the need for population control and limited space become a factor for those with the cure.

Dying Peacefully

One topic we’ve not touched on so far is death. If we remove the natural cap that the aging process forces upon us, then there won’t necessarily be a maximum age we can live to. However, death from anything not related to age would still occur. Currently, we think of death as an inevitable natural process although the causes of death can be many and varied. When asked to think about death and how they would like to die, the majority of people hope for a peaceful death during their sleep, at the end of a long and fulfilling life, and without pain. As we’ve already discussed, how fulfilled your life may be could already be compromised by denying you the right to bear children, so what about the rest of our ideal scenario? A long life? Yes. But pain-free in your sleep? That’s another story.

After dying of old age, the only causes of death that remain involve accidents, murder and other diseases that can affect anyone, not just the elderly. Discounting instantaneous (but still gruesome) death, any other situation in which a life is about to be ended will undoubtedly be accompanied by fear and pain. This is not to suggest that fear and pain are not part of dying of old age, but any hopes of peacefully dying in your sleep would be shattered. As people get older, the thought of death becomes more and more a factor in their life as something they have to come to terms with, but this will no longer be the case. Death will only be associated with terror and pain; with lying in hospitals fed through a tube; certainly without peace.

Legalising and actively supporting euthanasia, on the other hand, would be the only acceptable solution to this problem. Only then would the problem of the perception of death being necessarily negative be alleviated, but this raises yet more ethical problems, particularly among religious communities.

Conclusion

A cure for old age may bring with it the promise of an undefined limit to humanity’s lifespan, allowing us to do more than we ever thought possible; read more books, watch more films, and finally build that shed you’ve been talking about, among other things. On the surface, this seems idyllic, but only when you begin to scratch the surface do you reveal a swamp of ethical concerns that muddies this picturesque vision of the future. Living forever may require our lives to change so significantly that life might not be worth living in the first place.

It would seem that having our cake and eating it is simply not feasible. Would you really want to live forever if you could never eat cake again?

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I’d love to hear your comments and opinions.

Post from: Synchronium

Living Forever: Is It Really Worth It?

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