|Case Two: Harold Hilman’s attack on electron microscopy may have cost the British neurophysiologist his job|
Neurophysiologist Harold Hillman has a serious career problem. He’s out of step with his peers, and now he’s out of a job as well.
For 15 years Hillman has been leading a scientist’s version of a double life. On the one hand, he has done mainstream neurological research and been a respected teacher of physiology. On the other, he has been questioning, needling, and increasingly infuriating those fellow biologists who use electron microscopy to study cells. Hillman says that the things scientists do to prepare specimens for the electron microscope so distort the objects’ structure that all observations and conclusions are suspect.
Perhaps because of Hillman’s personal charm, he has until recently been allowed to plow his lonely—and, most would say, arid—furrow. But now his relentless challenge to the scientific establishment may have finally caught up with him. His employer, the University of Surrey, has forced him to take early retirement at the age of 57 and, in so doing, has posed an interesting question: If Human’s mainstream work has been up to snuff (and there is no strong evidence to doubt otherwise), is it possible that the scientific establishment has robbed society of valuable contributions merely to punish a dissenter?
From 1965 until earlier this year, Human had been a reader in physiology at Surrey University and director of the Unity Laboratory of Neurobiology. When contraction hit British universities in 1981, Surrey’s Department of Human Biology and Health was scrapped. Hillman remained director of the Unity Laboratory, but with its continued funding in doubt, the university has obliged him to retire. He claims it is because of his controversial scientific views and the notoriety they have brought; the university maintains that it is consistent with the policy of shedding staff over the age of 55 in areas where the research is deemed “below average.”
A physician with research degrees in biochemistry and physiology, Hillman has worked primarily in neurobiology and resuscitation, and this work has never raised controversy. But in the early 1960s, he made a fateful and disturbing discovery that put him on the path to heresy. Human found that when centrifuged, adenosine triphosphate changed its activity. This meant that many experiments probing this crucial substance could be wrong.
Did scientists laud Human for such an important discovery? On the contrary, he couldn’t even get the results published. He says that one referee for the Biochemical Journal even wrote that “to suggest that physical agents can have chemical effects is revolutionary” and, by implication, absurd. (This criticism, of course, is itself ludicrous; as Hillman points out, grinding or stirring or centrifuging puts energy into the system, which can drive chemical reactions.)
Perturbed both by his findings and by their negative reception, Human began to investigate the effects of other experimental techniques. He observed that for some enzymes only 20% to 30% recovery is recorded, and concluded: “So we know prima fade that the technique is changing them.” Yet he couldn’t get funding to do the control experiments he believed necessary to put such techniques as chromatography, biochemistry, or electrophoresis to the test.
He was reduced to laying out his arguments in a book entitled Certainty and Uncertainty in Biochemical Techniques (Surrey University Press). But when the book appeared in 1972, the reviews were almost uniformly hostile. The most common complaint was that the arguments were old hat—the problems of preparation artifacts and degradation had all been solved or corrected for in the early days of the techniques. However, no one has answered to Hillman’s satisfaction the questions of when these confirmatory tests were ever done and where they were published. He believes to this day that no one has ever bothered to do the control experiments.
Still, one reviewer made a point that Hillman was prepared to ac cept: Although biochemists make many assumptions when they break a cell up into its components—for instance, they assume the pieces work just the same way outside the cell as they do in the complete cell—they somehow manage to arrive at a consistent and coherent picture of how the cell works.
That answer temporarily satisfied Hillman; he stopped pushing his heretical positions. But a couple of years later, he was doing work on nerve cells with microscopist Peter Sartory. To get the best images, they used transmission electron microscopy (EM) and were astonished by what they saw.
“We noticed something so peculiar that we really couldn’t’ believe it,” Hillman recalls. “About 80% of the membranes in the cell appeared end-on, [as if the cell had been sliced through its center]. It took Sartory and myself several weeks to realize that it simply wasn’t possible.” Yet that is what virtually all electron micrographs and illustrations in papers and textbooks show. “That was our first shock,” says Human. That implied that every electron microscopist was cutting virtually everything in the cell perfectly at right angles.”
According to conventional thinking, cell membranes consist of two layers. In stained EM sections the two layers show as two parallel lines of dark stain, like railroad tracks. But, Human observes, however you cut a cell, the two lines are always the same distance apart in the EM image. He draws the analogy of a chef cutting an orange. If he slices it clean through the center, the sliced surface will show a thin rim of peel. If he cuts it with a glancing blow, so that only a small slice is taken off, the peel won’t be cut at right angles—it will show as a much “thicker” rim. Human reasons that because the rim is always the same width in EM sections, it cannot represent a thick two-layer membrane. Rather, he believes, it is a single thin membrane stained on both sides.
“I have challenged electron microscopists to make a three-dimensional model of any living cell in which this [a membrane appearing to have identical thickness however it is cut] is so. It simply isn’t possible. All the stains they examine them with are heavy metals that deposit on both sides of the membrane, thus any real membrane will appear as two lines.”
According to Hillman, the consequences are profound. He insists that any experiment involving electron microscopy is incomplete and its conclusions cannot be justified. In an article in The Practitioner last year (July 1987, Vol 231, page 998), he suggested that the problems with techniques used to study cells were one major cause of slow progress in understanding such diseases as cancer, multiple sclerosis, and Alzheimer’s disease.
Flawed cell pictures are only part of the problems inherent in these studies, says Hillman. He also feels that a string of other hypotheses, crucial to this research—the existence of receptors that no one has ever seen, for example--are unproven yet accepted as gospel. In the article he likened medical orthodoxy to a religion, with its preisthood and theology.
Hillman’s reasoning is simple, attractive—and wrong, according to virtually every cell biologist and electron microscopist. It’s not as if the problems of preparation artifacts were unrecognized. As Audrey Glauert, head of electron microscopy at the Strangeways Research Laboratory in Cambridge and herself one of the pioneers of the technique, told The Scientist, “Every electron image is an artifact. With EM you’re a long way from the original cell—you’ve treated it and sectioned it and fixed it and done all kinds of things to it.”
But the fixation techniques have been compared with other microscopic preparations, and cell biologists are generally satisfied that EM features correlate with living cells. Furthermore, even if the preparations do distort the cells, there seems no good reason why all the different techniques should produce identical artifacts.
Hillman will not accept these arguments. He asserts that established EM researchers have much to lose in career terms if they were to admit their research has been based on faulty technique. And he claims EM manufacturers denigrate him because they have a vested interest in the status quo.
Not so, say manufacturers. Bill Clarke of Philips Analytical puts it simply: “No one came out and supported Hillman, so in a sense it was a democratic vote.
Surely, it’s harmless enough if a lone researcher (Sartory died in 1983) chooses to disagree publicly with the received wisdom, isn’t it? No, say specialists like Glauert. “Some of the things he was saying were destructive and not helpful [for science],” she says. She is particularly upset that in their quest to get published, Hillman and Sartory wrote their ideas up for School Science Review, a journal for science teachers (Vol 62, page 241, 1980). Robert H. Michell, John B. Finean, and Roger Coleman of Birmingham University, authors of one of the textbooks included in the general attack by Hillman and Sartory, thought so too, and wrote a detailed defense of “this essential component of the intellectual toolkit of every working biological scientist” in a later issue of SSR (March 1982, page 434). “They [Human and Sartory] have signally failed to gain converts to their view among academic scientists, so they now seek, through the SSR, to persuade teachers to present their generally unaccepted and, we believe, mistaken view to our children.”
The reaction of the scientific community, however, has gone beyond censure of Hillman's charges; rightly or wrongly, Hillman’s extravagant claims have made it more difficult for him to do his mainstream work. “I cannot now get research funds for my work in resuscitation, which is absolutely respectable and totally different,” he says. His heresies have also blighted his academic career. He believes that his notoriety was directly responsible for the removal of his teaching responsibilities in physiology during the 1970s—”despite,” he says, “the fact that I have always taught what was in the textbooks because I want my students to pass their examinations.”
John Estall, one of his former students from those days, remembers him as an “inspiring” lecturer. Now principal of St. George’s College in North London, Estall told The Scientist “I thought he was a very good teacher—the others at Surrey were as dull as dishwater. He probably was always a little controversial—it made him outstanding in that environment, and I can still remember being enthused by him.”
Colleagues appear to like Hillman personally. “He’s zany,” Peter Goodhew, director of Surrey’s Microstructural Studies Unit, says. “He breezes in with a cry of ‘Beam me up, Scotty!’ His heart is genuinely in the right place—he has done fine work for Amnesty International—but he lets his eccentricities carry him away, and he won’t back down when he’s wrong. I think it would strengthen rather than weaken his case if he sometimes admitted he was wrong.”
Hillman maintains that he always listens to his critics, notes their objections, and takes them away to ponder over. “I never dodge a single question,” he says, “and there am times when I have admitted we were wrong.” Nevertheless, these are always on peripheral issues; terrier-like he clings to the core of his beliefs.
So Hillman has now had to face the ultimate career sacrifice. Surrey has decided to close his lab. The vice-chancellor, Anthony Kelly, said that this was done following a survey of the university by the University Grants Committee, the government funding authority. The UGC concluded that certain aspects of Surrey’s science, including the remaining parts of the biology department, were below average.
Hillman claims that his laboratory was not specifically assessed by the UGC and should not have been included with the others. UGC assessments are partly based on scientific reputation and partly on success in attracting outside finance. Hillman admits that he can’t get any research grants because any peer-review committee is bound to have an electron microscopist: “They don’t simply disagree with me,” he says, “they have a venomous hatred of me.”
His laboratory has some charitable funding, which will enable him to complete an atlas of nerve cells. But if he can’t obtain further funding, then he will have to retire from active research this summer and concentrate on writing.
Goodhew says that Hillman “has been pretty unbending in his opposition to the system. If the system was more affluent it would have been fine to have him about, but we all need to justify our support now.”
Several microscopists were surprised when contacted by The Scientist. “I thought all that was finished seven or eight years ago” was the common reaction. But for Hillman it’s never over. “I believe the question has gotten onto a theological plane. That is, instead of a proper scientific debate they’ve in effect declared me a heretic,” he sighs.
The high priests of biochemistry have, so to speak, excommunicated Human. But one can imagine him going into retirement still clinging tenaciously to his heresies.
Richard Stevenson is deputy editor of Chemistry in Britain.