The Case of the Unknown Dosage

This column is a second-hand mystery thriller on the lines of the Agatha Christie Poirot television series. It tells the story how a real-life scientific scandal that involved a Nobel Prize winner, great American and U.K. universities, the Manhattan Project, several expert U.S. government committees, and dirty work at the laboratory was exposed by an academic detective almost a hundred years after it was first committed. Maybe it’s a mystery that would be solved easily by Poirot or by anyone familiar with those civilized British murders which turn on how much arsenic was in the jam omelette. But no one knew there was a mystery to be solved. And even though billions of dollars may hang on their decision, the authorities have not yet agreed to re-open the case.

The Hercule Poirot in this case who’s seeking the truth, whatever the cost to distinguished reputations, is Edward J. Calabrese, Professor of Toxicology at the University of Massachusetts, School of Public Health and Health Sciences, at Amherst. As in the best thrillers, Professor Calabrese blundered into the scandal by accident when he attended a research conference that starred two different sets of elderly rats. He was struck by the difference in their appearance.

Some looked “remarkably healthy, showing a wonderfully shining coat of fur. They seemed to be in the prime of their adult life.” Others “looked unhealthy, very haggard, skinny, with very little fur, and that patchy and dull.”

Nothing odd there, you might think, because the study of the rats was being conducted to determine the effects of exposing them to high doses of background radiation, sometimes sixty per cent higher than the background radiation they had experienced throughout their lives. But something odd was there because the healthy, shiny-coated rats were the ones who had been subjected to massive doses of radiation while the ailing, haggard, and dull creatures were the control group living protected lives. And that comparison contradicted the orthodoxy of public health and regulatory authorities holding that any dosage of radiation, however small, was bound to inflict health damage on living creatures.

A dose a day keeps the doctor away.

That belief in turn was confined neither to scientists nor to health professionals but had spread throughout society to promote strong risk-averse attitudes across the board but especially on the topic of radiation because, like cancer, radiation was a silent killer that murdered us without our noticing.

Most of us might have reacted to the rats therefore  as if it were an anomaly we hadn’t yet detected with some such thought as “well, that’s odd, wonder what caused it, probably something in the water.” But chance favors the prepared mind, as Louis Pasteur once said, and Calabrese, who had written several books on the topic, looked at the data and concluded that it was hard to deny that radiation had exerted a positive healthy influence on the rats. And for him that meant the conventional theory had to be re-examined.

The theory he was challenging is described by Calabrese as follows: any dose of chemical carcinogen or ionizing radiation, no matter how low, has the potential to cause cancer and shorten our lives. He traces the origins of this theory back to 1920 and to a Nobel Prize-winning scientist, Professor Hermann Joseph Muller, who in 1926 demonstrated that high doses of radiation could cause gene mutations in the fruit fly. That made him famous and won him the Nobel Prize in 1946.

But it was a limited scientific advance, and as interest in combating cancer grew, he sought to expand its application to consider the impact of X-rays on the health of the patients. He asked research students to test whether the gene mutation response was proportional to the dose of radiation administered in other cases. They found that it was. But the radiation dose was extremely high in their experiments—"hundreds of thousands to millions of times greater than background radiation.”

Rather than test what was the effect of very low doses of radiation, however, Muller extrapolated backwards or downwards to estimate the impact of such doses. He called these results the Proportionality Rule. And this linear no-threshold model or LNT (i.e., implying that there’s no threshold below which radiation is harmless or even beneficial) became over time the orthodox view—and so the basis of “precautionary” principles that sought to eliminate any risk whatever from radiation even at the cost of eliminating fuels and technologies beneficial to human flourishing.

It took time for the LNT to establish itself, however, because the LNT was controversial within medical science and because Muller and his colleagues found it hard to replicate the results in other experiments without heavy massaging of the data. In some cases Muller went beyond massaging data to outright misrepresenting it. When Muller received the Nobel Prize for his original research in 1946, he used his acceptance speech to claim that the “threshold model” had been definitively superseded by the LNT. As Calabrese says darkly in his essay in Reassessing Radiation Safety (The Global Warming Policy Group, London): “In effect, Muller deliberately deceived his audience in an effort to manipulate them into accepting his ideological perspective.”

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That was a serious violation of the procedures and ethics of science. But it need not have been the end of the matter. There were many occasions after 1946 when the LNT theory was supposed to be reconsidered by different scientific authorities. Indeed, for more than half of his investigative essay, Calabrese is describing how on one occasion after another scientific authorities who ought to have discovered the errors underlying LNT failed to do so, from causes both shocking and comic. At one time Muller and a colleague successfully dismissed criticisms of their position because they knew the evidence against them was in research documents classified by the U.S. government and thus unavailable to reporters or the public.

From 1946 to the mid-nineties in Calabrese’s telling, the LNT becomes a plot device like Alfred Hitchcock’s McGuffin which, as it passes from hand to hand, escapes any number of threats of impending detection and discrediting until in 1995 an Oak Ridge genetics researcher in Tennessee discovers major irregularities in earlier researches that had apparently supported LNT. That leads to further investigations which themselves result in the conclusions that LNT was a mistake (even if its consequences remain to be buried), that those subjected to low-dose radiation did no worse than their control group, and that there was even a “hormetic” effect, i.e.,  low-dose radiation was beneficial, as with the rats which started Calabrese on his voyage of discovery.

It's a complicated story but also a gripping one that Calabrese tells well and clearly. My brief summary is not a substitute for the monograph which you can read above. But the LNT story is not over. Though the scientific basis of LNT has evaporated, its consequences in terms of policy and regulation are very much alive.

First, at a time when government policies everywhere are looking for alternatives to fossil fuels that are both effective and reasonably priced, nuclear power stations are still being blocked by massive and expensive regulations that reflect a false and vastly excessive estimate of the risks of radiation. Reassessing Radiation Safety is highly topical and an important intervention in the nuclear debate.

Secondly, the story of Muller and LNT illustrates the danger of treating human scientists as the god, Science. Borrowing a remark of Chesterton another topic, we might say about Calabrese’s story: “We believe in science as much as we ever did, but—Oh--there was happy time when we believed in scientists.” Scientists themselves should welcome their liberation from divinity.

Thirdly, since the LNT was a rehearsal for the precautionary principle which, inter alia, is a device for stopping the kind of innovation that we need for purposes as various as climate policy and cancer research, we should cast a beady eye on how that logic looks in the light of Calabrese’s careful account.

But let the last word go to Lord Lilley, a Cambridge-educated scientist and a member of Margaret Thatcher’s cabinet, who returns to the main point in his introduction:

Professor Calabrese has shown that a great many things that are damaging in large quantities may – in small doses, below a certain threshold – do no harm or even be beneficial. It seems that very small doses of potentially damaging substances can stimulate the repair and protection mechanisms that our bodies have evolved to help us survive.

You can have 'too much of a good thing.' But can you have 'too little of a bad thing?'

The sooner we find out, the better.

Les Miserables

In George Bernard Shaw’s Play, Misalliance, a young socialist bursts into a upper-class weekend party  waving a gun, and after a good deal of Shavian talk he’s persuaded to postpone revolution for a square meal in the kitchen by the kindly matriarch of the household. Before he is diverted, however, he challenges a retired colonial governor to say how he would deal with the New Socialist Man of the future, like himself, who rejects all the conventional rules of the political game. The governor explains matter-of-factly that he would tip off an ambitious policeman that he was a bit of a troublemaker who should be watched and then wait patiently for the policeman to provoke him into a fight and an arrest.

“Why, that’s disgraceful,” responds the anarchist indignantly. The governor replies that in the game of anarchism the police can always beat the anarchist.

Almost invariably, that is true. Revolutions are the exception, and even they conform to the governor’s cynical insight when they succeed, because the police reappear soon after the new order is established, are given greater powers by the new post-anarchist authorities, and arrest the few remaining anarchists. See the history of the early Soviet Union passim.

What we’re at present witnessing is the spread of anarchism in the United States and, less violently so far, in the United Kingdom: mobs rushing around, pulling down statues, attacking people they believe to be “racists” (maybe because they’re wearing a baseball cap), demanding conformity to their  revolutionary slogans, and visibly flouting the authority of governments and local authority. The pulling down of statues—historically known as iconoclasm—is a traditional accompaniment to religious or political revolution that symbolizes the defenestration of one set of rulers and their replacement by a new set.

The role of the police in these events is especially significant. As the guardians of order, supposedly politically impartial, they are expected to restrain and suppress riots and destruction of lives and property. Against these disorders they seem pulled in three different directions Those in Seattle have been instructed by local authorities that are politically sympathetic to the rioters to allow them to establish “no-go” areas outside the law; those in Atlanta may be resigning or simply looking the other way when crimes are committed because they feel the local authorities are making them scapegoats for incidents of law enforcement that went wrong; and those in London seem to have decided on their own initiatives that policing by consent means the consent of the rioters and have accordingly tried to appease them. In all these cases the citizens can no longer rely with confidence on the normal assumption that the police will protect them and their property. Anarchy reigns.

At some point if the anarchy does not lead to an actual revolution, it will either fizzle out or be stopped by police or military force. The 1968 manifestations in Paris were stopped when the Army made it plain it would intervene if necessary, the bourgeois supporters of de Gaulle mounted their own massive manifestations in Paris, and the Gaullists won a landslide in the subsequent elections.

But the spirit of anarchy cannot be confined in a box marked public order. It seeps out into all aspects of our lives—I’ve mentioned iconoclasm as its symbolic representation in the arts. Jihadists have destroyed “pagan idols,” i.e., Buddhist images, in Asia. Feminists in recent years have been imitating the Victorians in putting bras on Greek statues and stockings on piano legs in official settings. And the removal of statues of national heroes such as George Washington, as well as leading abolitionists, on the grounds of “slavery,” shows that the real motive force of this particular anarchistic drive is to replace the United States, founded circa 1776, with a new American state.

More important than iconoclasm, however, is antinomianism which is the rejection of all laws, customs, and informal rules in all fields of human behaviour including, significantly, science, law, and morality. Their removal gives the anarchist a thrill of liberation when first antinomianism breaks forth. But since it’s in the nature of man that, as Burke said, he must have rules to govern him, and if they don’t come from within in the form of customs and practices, they will come from without in the form of politically-imposed new “truths” on the arts and sciences.

Seattle, 2020

It’s a two-stage process: first, we liberate ourselves from the old laws that confine our imaginations to what science and experience tell us is true and practicable; second, we replace them with rules that reflect the wishes and interests of the powerful—who are not always politicians and ministers but sometimes in periods of decaying political authority, the mob or its allies. The political mob made its first appearance in Paris during the French revolution, but it has come and gone many times since then, and it’s presently most powerful in Seattle and Portland.

Taken together these two stages produce the replacement of professional rules and ethics by political values and authority in all fields. It can be a slow process, especially in science, and it begins modestly, but the final stages often have seasoned professionals accepting new rules they would once have denounced or regarded as simply too absurd to bother denouncing. The old professional rules of American journalism that you followed the truth where it led by examining fairly the claims of all sides in a dispute have collapsed entirely—and that collapse began long before Donald Trump was elected President. It has reached its apogee in the recent decision of the New York Times to publish the deceptive and false 1619 Project not as one account of many historical accounts of the birth of America but as the sole acceptable truth (though it comes to us less from history than from critical race theory which is constructed so as to negate any criticism of its own criteria.) Its principal author has just welcomed the spreading anarchy as a vindication of the Times project, which is now to be taught in American high schools.

Examine now this sinister drift from the rules of scientific truth to the imperatives of political anti-science which we might call the Lysenko Imperative, or “What the Party says is Science is Science”:

  1. There is a replication crisis in science. For the last decade it has become an open or grumbling scandal that a very high number of scientific experiments cannot be replicated, which means that the original findings are invalid. Since a great number of findings are not tested for replication in this way, that implies much more uncertainty about scientific findings than we tend to assume. Replications are far lower in psychology (50 per cent) especially social psychology (25 per cent), and in medicine than in other fields. In the last few days, for instance, a study by Carl Heneghan and Tom Jefferson of the Centre for Evidence Based Medicine at Oxford found that they could not replicate the results in 13 of the 15 studies purporting to support the two-metre distancing rule in SARs and Covid-19 cases and concluded that “poor quality research is being used to justify a policy with enormous consequences for us all.”
  2. Much of the writing on both pollution and global warming emphasizes that these problems constitute a crisis or an emergency requiring urgent action to reduce carbon emissions and other “pollutants.” Time and again the dates for which catastrophe was confidently predicted have passed without grave occurrences. No apologies have been offered, and no signs given that the forecasters were reconsidering the theories on which their forecasts were based. Like the replication crisis, the prediction crisis is a scientific scandal unless it is seriously addressed. The latest warning of this erosion of scientific standard comes from Professor Ole Humlum, who looks at the empirical observations of climate science (as distinct from computer modelling) and finds that in most respects, including some surprising ones, things are getting better. He points out  that new data on rising ocean temperatures raise interesting questions about the source of the heat. “We can detect a great deal of heat rising from the bottom of the oceans. This obviously cannot be anything to do with human activity. So although people say the oceans are warming, in reality there is still much to learn.” But that will depend on the willingness of scientists committed to the conventional view of global warming as something driven by human activity to question or moderate their outlook in the light of this disturbingly optimistic evidence.
  3. Where will these trends end up? As is already the case with the social sciences, the future of science could be its transformation into the political hopes of activist groups within the profession committed to views that reject traditional scientific rules as obstructions to their visions. "Feminist science" and "transgender science" both confront traditional biology as a hostile “essentialism” and treat those who disagree more as political enemies than as fellow-scientists. A more radical critique is mounted by those who want to decolonize "white science" (i.e., science)  by granting at least equal scientific authority to indigeneous religious world views. A journey around this set of ideas—or “new ways of knowing”-- is conducted by Lenny Pier Ramos in the current Quillette. It is a journey into the past and into pre-modern mind-set. “ I pushed this point and asked Dr. Tajmel [a leading proponent of this decolonization] if her project did not, ultimately, amount to the reintroduction of religion in science. She responded, without missing a beat, that science itself was a form of a religion."

Mr. Ramos reflects that given these trends it seems only a matter of time before Science and Nature get on board with that idea. It sounds alarmist but absurd. Yet we would once have thought the same of the "1619 Project" and the New York Times. And that's before the arrival of, first, the mob, and then the new policeman.