Opening Pandora’s Box

Demands for equal time cut both ways.

Armies of the night, science-writer and novelist Isaac Asimov once called them. He was referring to the countless millions of evangelicals who believe the book of Genesis to be literally true and therefore reject any evidence to the contrary.

President Bush is one of them. So is Michael Drake, principal of Auckland’s Carey College.

As reported in the Weekend Herald (27 August), Drake believes that one can provide dates for the main events in the history of the universe by adding up all the ‘begats’ in the Bible. The date of creation turns out to be just over 4000 BC, and that of Noah’s Flood about 2400 BC.

What can these young-earth creationists say when confronted by scientific evidence that the universe began more than 12 billion years ago, that life began over 4 billion years ago, that dinosaurs became extinct some 63 million years ago, or that fossils of our hominid ancestors are shown by potassiumargon dating to be more than three million years old?

Their best ploy is to say that God created the universe with all this contrary evidence built into it. This, says Drake, is “perfectly possible”. It seems not to bother him that this hypothesis makes God, not just a Great Designer, but a Great Deceiver as well.

And what about the ancient civilisations whose historical and archaeological records spitefully ignore the Flood and the death of all living creatures, other than the inhabitants of the ark? Clearly, God must have even more tricks up his sleeve. After all, as Drake points out, tautologically, “God is God.”

Most mainstream Christians outside the US would reject this version of intelligent design. Like fifth century St Augustine, they would say that biblical literalists deserve to be “laughed to scorn” for their “utterly foolish and obviously untrue statements.”

Adopting Augustine’s figurative interpretation of Genesis, liberal Christians believe they can accommodate the findings of science and history. Thus those who call themselves theistic evolutionists can, without contradiction, accept Darwin’s laws of natural selection as one of the laws of nature — along with those of physics and chemistry — with which God endowed his creation at the outset. No need for him to intervene on this account.

Enter a third version, one that reintroduces elements of evangelical creationism into the evolutionary story. Michael Behe, in his 1996 book Darwin’s Black Box, claimed that although evolutionary mechanisms can explain a lot, they can’t explain the emergence of certain highly complex biological systems. His examples include the flagellum of E. coli, and the human immune system.

These systems, Behe argues, are “irreducibly complex” in the sense that none of their simpler parts would have survival value until they were assembled in the right way by the intervention of a supernatural deity. Unlike theistic evolutionists, Behe believes God has to tinker with his initial design.

How scientific is all this? Well, Behe himself is a scientist. And scientists certainly do find complexity in the biological world, especially at the molecular level.

But is there scientific evidence that this complexity is irreducible? Scientists can literally see complexity. But they can’t see irreducibility. Behe has to argue for it. And his arguments have been found wanting by both philosophers and scientists.

Philosophers disparage his argument’s form: “We don’t yet understand how these complex forms could have emerged, so God must have created them”. It is a rehash of the ‘God of the Gaps’ fallacy. Flawed faith-based reasoning. Not sound evidence-based science.

Meanwhile scientists continue to plug those gaps with accounts of the evolutionary pathways that generated these supposedly irreducible systems. What becomes of Behe’s argument for an intelligent designer if all the gaps get filled?

Now to the important question: Should intelligent design be taught in schools? If so, which version?

Mary Chamberlain, curriculum manager for the Ministry of Education, says science classes should allow for some version or other. She seems to echo Bush’s recent call for ‘equal time’ for those who oppose evolution.

Equal time counts both ways. If equal time is to be given to those who think there are arguments against evolution, then it should also be given to those who think there are arguments against intelligent design. But then we get into what philosophers call “the problem of natural evil.”

If you think an intelligent designer designed the universe, then think about the unsavoury aspects of his design. Think of diseases like Alzheimers, cancer, smallpox, and those caused by Behe’s favourite, E. coli. Think of disasters like tsunamis, hurricanes, and earthquakes. If complex design demonstrates intelligence, then by the same token the “god-awful” nature of much of God’s design demonstrates defective or malevolent intelligence.

On reflection, do its promoters really want intelligent design analysed and evaluated in schools? And if so, by whom? Do they really want to open Pandora’s box?

Natural products chemistry – the road from nature to pharmaceutical

Many pharmaceuticals originate from nature, but their development is very different from that of so-called natural health products. This article was originally presented at the 2005 Skeptics Conference.

The field of natural products chemistry deals with the scientific study of chemicals isolated from living organisms. This can be anything from isolating indigo dye from woad, distilling lavender oil from the lavender plant, working with plant oils and animal fats to make soap, to trying to find the active ingredient in a plant extract that reduces fever.

Interest in compounds from living organisms dates back to the beginnings of civilisation. More recently it also gave birth to what we now call ‘organic chemistry’. Initially, organic chemistry was natural products chemistry, when people thought that carbon containing molecules were imbued with a ‘vital force’ and could only be made by living organisms — hence the name ‘organic’. Friedrich Wöhler shattered that idea in 1828 when he became the first to make urea (an organic molecule) from inorganic precursors. Now we define organic chemistry simply as the chemistry of carbon containing compounds.

Unfortunately this mystical feeling that “natural” things are somehow better, or special, has survived till today, and many people are still convinced that “it’s natural, so it’s got to be good!” When dealing with natural substances that have biological activity, one must ask why they have any physiological effect. The answer is chemical defense: plants that do not have thorns, for example, have evolved chemical substances to poison animals that would otherwise eat them. The ‘natural’ effect of any herbal product then, is to make the user sick! We should not be talking about ‘natural is good’, but about chemical warfare.

Chemical warfare

The mould Penicillium notatum produces and secretes an antibiotic, a compound that inhibits bacteria that could compete with it for food or resources. This is chemical warfare on the microscale, a life and death battle for survival between the mould and its enemy. The mould certainly does not make the antibiotic for the benefit of mankind — any beneficial effect to us is an accidental advantage. But we can certainly make good use of that! The antibiotic in question is of course penicillin, the first discovered antibiotic. It has revolutionised medical treatment of bacterial infections and earned its discoverers Sir Alexander Fleming, Ernst Chain and Sir Howard Florey the 1945 Nobel Prize in Medicine.

We certainly exploit this type of biological activity to our great advantage. Natural products, or compounds derived from natural products, comprise the majority of pharmaceuticals in use today. So what is the difference between them and ‘herbal remedies’ that are sold in health shops and supermarkets?

The big difference is that herbal remedies are not tested. Not tested for efficacy (we don’t know whether or how they work), they are not tested for safety (we don’t know whether they are toxic or have side effects). They are not regulated in any way, so you don’t know what you are buying at all!

Drug development process

Before a natural product can be approved for use as a human pharmaceutical, it must go through a rigorous process of testing during clinical trials. And before it even enters those, it must be fully identified and characterised. This precise analysis is what makes the known and well understood pharmaceuticals stand apart from herbal remedies. For the most part, we know very little, if anything, about their chemical composition and effects.

Once the initial discovery process is complete, the natural product is subjected to a barrage of tests in vitro (in the test tube) and in vivo (in lab animals). Once biological activity and initial safety is demonstrated, the potential pharmaceutical can be admitted to the Phase I clinical trial. This involves a small group of healthy volunteers who are given the compound to determine its safety (that is, evaluate any toxicity and side effects) and tolerated dosage. Phase II trial follows, where the effectiveness of the compound at curing a disease is finally tested on a small number of human patients.

Finally, Phase III is a large scale trial on 1000 to 3000 patients, verifying effectiveness and monitoring any adverse effects from long term use. At the end, all the data are submitted to the monitoring agency (in the US this is the Food and Drug Administration) for evaluation. Once approval is given, the drug can be launched onto the market, where it still undergoes long-term safety monitoring and additional tests during the so-called Phase IV trial.

On average, out of 5000 compounds that undergo pre-clinical testing, only five are deemed promising enough to enter clinical trials. Out of those five, only one is approved — others fail because they do not show effectiveness once trialled in humans, or exhibit unacceptable levels of toxicity or side effects. From discovery to prescription, the whole process takes on average 12 years, with costs estimated to be in the hundreds of millions of US dollars.

While the process may not be perfect, it does attempt to ensure that the medication we are prescribed is first of all safe, and that it works. Herbal remedies cannot claim the same.

The Story of Taxol

In the 1960s the National Cancer Institute (NCI) launched a screening programme to test various plants for potential anti-cancer activity. Over the next two decades they screened more than 114,000 plant extracts. This included, in 1962, a collection of bark from the Pacific Yew, Taxus brevifolia. Immediately, this shrub generated great excitement as it showed interesting activity in biological assays. A research project was launched to investigate these properties, and in 1967 the active ingredient was isolated and named paclitaxel. The structure was not solved until four years later in 1971, a reflection of its high degree of complexity. Paclitaxel exhibited a broad spectrum of activity against cancer cells in vitro, and in 1979 scientists discovered its mode of action in the cell — a completely novel way of stopping and killing cancerous cells. In vivo testing showed phenomenal successes — paclitaxel stopped the growth and even shriveled breast cancer tumours in mice. All of these results made paclitaxel the hottest natural product around. Everyone wanted to get their hands on some, but paclitaxel had many hurdles yet to overcome.

Researchers rushed the compound into clinical trials, but immediately faced a problem. Paclitaxel was not soluble in anything. As one researcher put it, “it had the solubility of a brick.” How were they going to administer it to patients? Finally a concoction consisting mainly of castor oil was found to be effective, but was almost the drug’s undoing. Paclitaxel proceeded to clinical trials, and was almost rejected right then and there, as it showed unacceptable levels of side-effects. Fortunately, someone figured out that most of these were due to the castor oil, and after the formulation was changed somewhat, the drug continued to Phase II clinical trials.

The results were astonishing: against the most virulent forms of ovarian cancer, paclitaxel showed unheard of levels of response. Doctors and researchers were suddenly clamouring for more and more of the drug. But Taxol faced its greatest challenge yet: that of supply.

The compound paclitaxel is present in only minute amounts in the bark of Taxus brevifolia. Fifteen kilograms of the bark yield barely half a gram of the active compound, which means it would take six 100-year-old trees to treat one patient. Quite aside from the ecological impact of the large scale logging operation required, there simply are not enough Pacific Yew trees in the world to treat all the cancer patients.

Making the compound in the lab was not an option. Though a successful synthesis of paclitaxel was reported in the literature, the molecule was too complex for this to be a viable route to obtaining large quantities. Fortunately however, researchers discovered that the much more common English Yew (Taxus baccata) contained relatively large quantities of a compound that is related to paclitaxel. Eventually in 1989 they succeeded in transforming this 10-deacetylbaccatin into paclitaxel. This semi-synthetic pathway is how Taxol is made even today.

The billion dollar wonder molecule

Having successfully completed clinical trials, paclitaxel was launched onto the market in 1993 under the trade name Taxol as a drug to treat ovarian cancer. Sales of Taxol grew exponentially, rapidly reaching and passing the US$1 billion mark. Today, Taxol remains the leading treatment against ovarian, breast and lung cancers, and Karposi’s sarcoma. Yet it had not been an easy journey: from bark to drug it took 31 years, and with an estimated cost in excess of US $300 million.

Victoria University Marine Chemistry Lab

Most of the natural products that have “made it” as pharmaceuticals come from the terrestrial environment, not surprisingly, as terrestrial plants, animals and fungi are most easily accessible to researchers. In the last few decades however, with the advent of scuba diving, a whole new world has opened up: the marine environment. The Marine Chemistry Lab at Victoria University studies chemical compounds found in marine plants and animals. We examine a wide variety of organisms, including sponges, seaweeds, sea-slugs and others. Our ultimate goal is to discover new, biologically active chemicals from marine organisms and develop them into pharmaceuticals.
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Discovery of peloruside

In 1998, Lyndon West (who was at that time doing his PhD in our lab), discovered a new compound from the sponge Mycale hetsheli. He named it peloruside, after Pelorus Sound where the sponge came from. The compound looked very interesting right from the start, so patents were filed right away, and biological testing initiated. Indeed, exhaustive in vitro tests revealed that peloruside had the same mode of action as Taxol! This news generated a lot of interest, and in 2004 a deal was signed with Reata, a US Pharmaceutical company. Their tests in mice showed very promising results: injections of peloruside into grafted tumours radically reduced their growth. With exciting results like that, everyone is now keen to start clinical trials.

Unfortunately, we face a supply problem even worse than the Taxol people did: the compound is once again present in only small amounts in the sponge. In addition, sponge populations are scarce in the wild, and difficult to reach. They also show a large variability in the amounts of peloruside they produce, depending on depth, season, geographical location and even individual animal.

Aquaculture

But, we have a solution: aquaculture! Fortunately for the project, the sponge can be propagated from small cuttings. We have taken bits of wild sponges and tied them to ropes that have been suspended off the anchor lines of a mussel farm in the Marlborough Sounds. The sponge has grown well — our sponge farm yielded almost 100 kilograms of the sponge in 2005. Some of this mass was returned to the ropes to grow again for this year, the rest has been harvested and is now being processed in our lab. We hope to get gram amounts of peloruside and hopefully start clinical trials with Reata Pharmaceuticals in the US this year.

Could peloruside be the next wonder drug against cancer? Well, it has a long way to go yet. But it certainly shows promise, so watch this space.

Newsfront

In a decision which sets an important precedent for US science education, a court has ruled against the teaching of the theory of ‘Intelligent Design’ alongside Darwinian evolution (BBC, 20 December). The ruling comes after a group of parents in the Pennsylvania town of Dover had taken the school board to court for demanding biology classes not teach evolution as fact.

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At last, something decent on telly

It was refreshing to see Jeremy Wells discussing conspiracy theorists, Paul Holmes, Jonathan Eisen, the Skeptics and wolverines, on TV2’s Eating Media Lunch in November. Best line: When it comes to pointing out f*ckwittery, the Skeptics are usually on the money. For those who missed it, the Skeptics Video Library has a copy on DVD.

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David Lange vs the scholars


Checking facts should be part and parcel of academic life, but too often it isn’t done.

The late David Lange opened his 1990 book Nuclear Free: the New Zealand Way with a remarkable story. He wrote that on a winter evening in 1962, he was 20 years old and walking home near Auckland when he saw a blood-red moon and shafts of light in the sky:

They were red and white. They extended across the night like the ribs of a fan. They were spinning, they were intermingling. The sky was diffused with a ghastly brush of red. It was an unnerving spectacle. Lange’s book says he soon learned from the radio that the United States had tested a nuclear bomb by launching it on a rocket and exploding it above Johnston Atoll, which lies in the North Pacific, about 1300km southwest of Hawaii. The sight of a nuclear explosion disturbed him, Lange wrote, and he was haunted thereafter by the fear of nuclear war.

Scholars have dismissed Lange’s story. In a 1994 article in the Journal of Imperial and Commonwealth History, historian GP Taylor from Sheffield University denied that Lange or anyone else in New Zealand could have seen any such display. In the perverse article — the point of which was to justify France’s bombing of the Rainbow Warrior — Taylor wrote:

His religious upbringing coupled with a lively imagination seem to have affected Lange here. Johnston Island is over 4000 miles from New Zealand and the impression he gives of what he saw was impossible from that distance.

It would have been easy for Taylor to check the facts. He simply had to look in the New Zealand Herald for the winter days of 1962 to see if there were reports of a spectacle in the evening sky. The Journal of Imperial and Commonwealth History is a refereed periodical, and it would have been easy for the anonymous referees of Taylor’s article also to check his claim that Lange’s story was false. None of these scholars did the job. In fact, a big photograph of the sight covered the top of the front page of the Herald on 10 July 1962. The photo was captioned: “The spectacle in the Auckland sky shortly after 9 o’clock last night.” Under the headline ‘Aurora’ Lights N.Z. Sky, the newspaper described the sight:

A deep red “aurora” striped with jets of white light swept in a broad band over the New Zealand sky after 9 p.m. last night — seconds after a United States task force exploded a high altitude nuclear device of “megaton-plus” power over Johnston Island — 4000 miles to the north.

Watchers from Whangarei to Central Otago reported the eerie glow. An astronomer theorised in his Herald column that the results of the blast were visible in the South Pacific because:

“the electrons released by the bomb dropped quickly to the level where auroras normally occur, between 80 and 120 miles, and then dashed rapidly along the line of magnetic force which links Johnston Atoll with the north and south magnetic poles and which travels over New Zealand.”


After finding the story on the front page of the Herald, I wrote an article about the effect of the sight on David Lange and on the development of anti-nuclear attitudes in New Zealanders. My article mentioned how GP Taylor — and, by implication, the Journal of Imperial and Commonwealth History — got it wrong. I submitted the article to the journal. The referees rejected the article and did not even suggest how I might revise it to make it acceptable. Neither did the Journal of Imperial and Commonwealth History print a correction to their earlier article.

This year, Victoria University political scientist Jon Johansson published a book, Two Titans, about Rob Muldoon and David Lange’s respective prime ministerships. Johansson repeats Taylor’s blunder, writing on page 142:

Lange’s connection of an unusually red sky to a nuclear test is also, one must add, highly implausible. The earth’s rotation alone renders Lange’s anecdote an illusory one, but illusion is also part of the anti-nuclear story, notwithstanding its central position in New Zealand’s contemporary political culture.

Neither Taylor nor Johansson nor the referees in Britain or New Zealand bothered to check whether or not the former prime minister of New Zealand was telling the truth before they alleged he was deluded. As for my article? It was published in Auckland University’s e-journal Asia Pacific Cultural Studies and is online at www.apcsjournal.org/pdf.php?type=article&id=5

The article will earn me a small tick on my PBRF report. Had Taylor published his article recently in New Zealand, then he also would get a tick. His tick would probably be bigger than mine because of the status of the Journal of Imperial and Commonwealth History. Johansson’s book will earn him a big tick. Hopefully, the substantial issue of David Lange’s reputation will not be lost.

“Treatment” for suffering just creates the disease

For those of us who learnt of the tragedy through the media, the anguish and grief of the family who lost their two youngest children in the icy depths of Lake Wakatipu is painful even to imagine. We know their lives will never be the same again. So it was comforting to read that the people of Glenorchy are doing what close-knit communities always do in times of adversity.

“The 111 call on Friday night, made by the children’s father, Stefan Poplawski, brought not just the emergency services to Greenstone Elfin Bay Station, but scores of local residents – by boat, car and helicopter. Some came to assist the commercial divers attempting to retrieve the lost children … others came to give whatever comfort they could.”

A police officer reported that the community had rallied protectively around the family, so we can be confident that the sensible, good-hearted people of Glenorchy are giving the bereaved family the comfort and practical assistance they need. The school mates of the Poplawski children are not so lucky. They’re being offered counselling.

Why? Sure, the accident was a terrible tragedy, but tragedies are nothing new and neither is the suffering they cause.

Throughout human history, people – both adults and children – have shown themselves to be remarkably resilient. Whenever and wherever tragedy strikes there is always strength and solace to be found in adversity. What is new in our modern world is the propensity of mental health practitioners to pathologise ordinary human suffering. These so-called experts want us to believe that suffering is no longer part of the human condition; these days suffering is a disease in need of treatment. A whole industry has grown up around this belief. Now, when adversity strikes, ACC-funded trauma counsellors descend on the unfortunate community in droves. And here’s the rub: trauma counselling doesn’t work. In fact, trauma counselling does more harm than good.

There have now been over a dozen controlled trials in which people involved in accidents and other traumas were randomly allocated to receive or not receive counselling. The results showed conclusively that counselling immediately after a traumatic event does not work. Those who received it were no better emotionally than those who did not. Worse, the better studies with longer follow-ups showed that receiving such counselling increased the rate of later psychological problems. The group that seemed to be harmed most by this were those who were particularly upset at the time – exactly those who you might think ought to be treated. So immediate post-trauma counselling may help us feel that something is being done, but it doesn’t help those who receive it. The fundamental problem with trauma counselling seems to be that asking anyone to talk to a complete stranger about their feelings while they are still raw with pain just makes things worse.

For most mentally healthy people – including the children of Glenorchy – not talking about it is often the most appropriate immediate response to a disaster. No doubt, in their own good time, the kids will talk about the tragedy as little or as much as they want with their family and friends and teachers, for these are the people who know them best, and who know best what support they need and when they need it. Of course they will be anxious for a while, and in need of comfort. But, as always, there will be chores to be done, lessons to be learned, sports to be played. Day by day, life does indeed go on. These children don’t need counselling. As they learn to cope with adversity they’ve already got the best role models any child could have – the courageous and compassionate adults in their own community.

Originally published in the Otago Daily Times, 15 September 2005.

The Wedge’s thin edge gets blunted

The decision by Judge John Jones ruling that the promotion of Intelligent Design (ID) in schools is a violation of the constitutional ban on teaching religion, is at least a temporary victory for scientific integrity (Newsfront, p10). Previous attempts to get creationism into the American classroom have been more ambitious, notably a Louisiana act which would have mandated for biblical literalism to be granted equal time alongside evolutionary theory, finally struck down in a majority Supreme Court decision in 1987. The proposal in Dover, Pennsylvania, was modest by comparison. It required that teachers read a 159-word statement declaring evolution “a theory … [t]he theory is not a fact”, and stating that ID is “an explanation of the origin of life that differs from Darwin’s view.” The book, Of Pandas and People, was recommended for students who wished to understand what ID involves.

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Forum

The leading medical journal The Lancet recently published yet another analysis of trials of homeopathy. After examining 110 such trials, the Swiss researchers concluded that there was no convincing evidence that homeopathy was any more effective than placebo. In the accompanying editorial, the editor, Dr Richard Horton, made a comment which has an uncanny, and no doubt intentional parallel with the views of the founder of homeopathy over two hundred years ago:-

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