Chapter 8 - Comments from Individual Scientists
Scientific correspondence about capping and particle movement on cell surfaces. The names of scientists who have improperly reported the cell capping field in the scientific literature. It gives a sample of their responses when asked explain their reasoning and the inadequacy of those responses.
8.1 The Wave Model: Responses
8.2 Drs. T.R. Hesketh and J.C. Metcalfe (Cambridge University)
8.3 Dr. G. Koch (MRC, Cambridge)
8.4 Dr. D. Bray (MRC, London)
8.5 Dr. M.S. Bretscher (MRC, Cambridge)
8.6 Overseas Workers
8.7 Prof. M. P. Sheetz (Duke University, N.C., USA)
8.8 Prof. K. Jacobsen (Univ. of N. Carolina, USA)
8.9 What does it all Mean?
Summary
8.1 The Wave Model: Responses
"as it stands the book is sadly incomplete. It lacks the most important part: the reply of the person to whom it is addressed" (Paul Feyerabend)
This quote, from the dedication in Against Method, was about Feyerabend's disputant and friend Imré Lakatos, who had recently died. Had things been otherwise, Lakatos would have happily replied and the two philosophers of science would have published their conflicting ideas in a single book, each seeking to demolish the views of the other. The wave model is also incomplete: it too lacks this most important part, the response of those to whom it was addressed, but the reasons are different. Disputants of the wave model have had ample opportunity to reply but they have chosen not to.
The wave model as published by this author (Hewitt, 1979) derived from earlier studies by Durham (1974), while others, notably Oliver and Berlin (1982), have taken a similar view. The wave model has been advocated by several, fully qualified, serious scientists, yet most workers, particularly the most influential gatekeepers, have taken the view that it can be dismissed. They have been asked to explain their rejection of the wave model but they usually just claim there is no "proof" of it or offer no explanation at all. The wave model has been cited in the literature a little but not really discussed there. The main criticism advanced is an inability to "see" waves. The same workers then discuss membrane flow, a concept whose invisibility has not prevented its discussion. In any case, waves on cells have been visualised many times and "seeing" them seems a matter of choice.
Scientific hypothesis testing has it that science is a negative philosophy, you can prove theories to be wrong but you cannot prove them to be right. There is no such thing as proof, only disproof. Consequently, those who reject the wave model have a duty to explain how they come to reject it. It is not meaningful to assert the absence of proof. Even so -
- Reading the literature does not reveal why the wave model is considered wrong.
- Directly asking workers has been no more informative.
- Most strikingly, anybody studying the field today, including undergraduate students, will be positively taught that the problems have been resolved - in favour of the cytoskeletal model.
There are important issues of responsibility and accountability here. Scientists have a duty to report their fields and work accurately but opaque procedures make it difficult to ensure this responsibility is discharged. In the capping field there seems to be a prima facie case for saying it has not been. In any event there are certainly some unanswered questions. The first and most immediately important, question, "What reasoning led to the rejection of the wave model?" is to be addressed to the individuals concerned. Other questions, concerning the nature and extent of the scientific responsibilities, are better directed to the institutions concerned.
These questions can only be addressed by asking the people concerned. This and the coming chapters describe the results of asking them. The literature on capping is extensive and only representative examples of debate can be mentioned. British workers have been active and will be dealt with first but all the individuals mentioned are recognised as expert in the area of cell membranes and motility.
My work was done in the Department of Biochemistry, Cambridge University, where two other workers had an interest in capping, Drs. T.R. Hesketh and J.C. Metcalfe. They organised the department's teaching in this area, consistently omitting consideration of the wave model even after its publication. They reviewed the field when publishing the work of their own team, again omitting the wave model from consideration. (Corps et al. (1982); Pozzan et al. (1980)). Three models had been put forward, one from the same Department as themselves. Drs. Hesketh and Metcalfe chose to teach and review the field as if only two models were available, omitting to mention the one originating in their own Department.
Plainly they think the wave model is incorrect but when asked to explain how they came to this view, they are not willing to "comment on" the wave model. "No comment" is not a satisfactory explanation, it seems more an evasion of responsibility. After all, if they have grounds for rejecting the wave model, those grounds would contribute to debate. If no reasons exist for its omission, their actions seem misleading and are a falsification of the field. It seems disingenuous to portray the omission of the wave model as non-committal. These men are professional scientists who, pursuing their professional roles, have plainly and publicly taken a professional view. As professional scientists, they must have considered how their omission would be interpreted by a reader and would be aware of the impact of such disregard on quality appraisal through citation analysis.
Dr. Koch is one of three men working for the British MRC who have worked in the area. He advocates the cytoskeletal view and performed studies showing associations between caps formed from transmembrane proteins and the cytoskeleton. He left the field shortly after the wave model was published. Subsequent to its publication, I believe he reviewed the possible mechanisms at least once, omitting all reference to the wave model. At the invitation of Drs. Hesketh and Metcalfe, he also felt it right to teach the subject this way, in the Department from which the wave model originated.
Dr. Koch exchanged a number of letters, in which his questions were answered, but unfortunately he broke off the correspondence without replying to the questions addressed to him. It seems he regards the wave model as a "theoretical possibility" but his actions indicate that he thinks it an unrealistic possibility and has rejected it, though he is not willing to give his reasons. He believes the principal postulates of the cytoskeletal model have been established in "prototype" systems, a claim that is difficult to understand as there is certainly more than one version of that model; Dr. Koch, like other workers, has not clearly listed the postulates to which he subscribes. He is not willing to explain how he thinks lipids can cap or address other criticisms of cytoskeletal ideas; moreover, he declines further debate. When Dr. Koch did his work, the original cytoskeletal model was in vogue. It is unclear whether he still advocates this form of the model, or now supports the cytoskeletal flow model.
At the time, Dr. Bray worked at an MRC unit at King's College, London. He is now at the Zoology Department of the University of Cambridge. He has worked extensively on axonal transport, a field he and others agree, is closely related to capping and particle movement. He has reviewed the field a number of times without ever acknowledging the existence of the wave model. His book on cell motility (Cell Movements, Garland Publishing, 1992) is intended for students and teaches a view approximating the cytoskeletal flow model. The book appeared some time after my letters to him. He was also coauthor of "The Molecular Biology of the Cell" a major text book on cell biology which reviews capping as if only two possible mechanisms exist. It appeared in the early 1980's, some time before my recent enquiries, but after the publication of the wave model.
Eventually, Dr. Bray replied to correspondence and gave references to three papers which outlined views in line with his own. None of those papers cited or discussed the wave model. He was reminded that his actions had rejected the wave model and that what was needed was an explanation of this rejection. He replied that he was not prepared to reply to questions on the wave model and that I should "ask somebody else."
Dr. Bretscher is a major figure in the field and appears to have worked exclusively on it since the late 1970's. He has published widely, advocating the lipid flow model and his research seems directed solely to showing that it describes the mechanism of capping. His ideas are unquestionably wrong but, even so he has attained distinguished honours, being the editor of major journals and a fellow of the Royal Society. The wave model competes directly with his ideas but, throughout the whole of his work, he seems never to have acknowledged its existence.
One reply was received from Dr. Bretscher, followed by the information that he did not wish to engage in a long correspondence. His letter is reproduced in full here.
19th July 1990
Dear John,
As you know, I have never really understood the physical basis of your wave model: your replies to my questions when you gave a tea club talk in the Biochemistry Department several years ago did not clarify the situation.
As to the direction the field is taking there is, as far as I can divine, an increasing belief that particle migration is achieved by direct action of some part of the cytoskeleton. This is, of course, not a view that I share. There are two real problems in the field: (1) There exist several individuals who cherish their own models (and I am a fine example) and (2) there are relatively few experiments which shed light on the molecular mechanism of what is going on. Neither situation is surprising since any experimental evidence is very hard to come by and this allows all sorts of ideas to be tossed around. It also means that a particular view needs an active advocate to keep it alive: in the case of your wave model your absence from the fray may be leading to its being ignored. This, of course, has nothing to do with what is true or false, but more to do with personalities.
Yours Sincerely
Mark BretscherThe MRC is the largest Medical Research agency in Britain. In section 9.6 its then director, Sir Dai Rees, will be quoted, who describes this letter as "crystallising the essence problem," making it a pivotal document. For now, some of the observations Dr. Bretscher makes should be dealt with. Firstly, despite his observation that "this allows all sorts of ideas to be tossed about", only three models have been proposed, with variations in each. Dr. Bretscher has consistently reviewed this field, over more than 15 years, as if only two possibilities exist - this is a clear practical rejection of the wave model. My presence or absence from the "fray" made no discernible difference to his practices, neither did the support of other workers for the wave model.
Secondly, a model may benefit from an "active advocate" but my absence from the field is not causing him to ignore the wave model. It is Dr. Bretscher himself who decides whether to consider or ignore alternatives and it is for him to have reasons. Actions or omissions by others cannot force him in either direction. He accepts that the wave model "may be being ignored" but the phraseology, for example the use of the passive tense, seems evasive. Dr. Bretscher has ignored the wave model, that is why he was contacted for an explanation. As a major figure in the field, it is not surprising that others follow him. Ignoring the wave model is the same as rejecting it but he seems reluctant to accept ownership of his action, let alone its implications and consequences. He even seems to be transferring responsibility for his omissions to the shoulders of those he has decided to ignore. Scientifically, logically and ethically this is wrong, responsibility should not be so evaded.
Thirdly, it is hard to comprehend how a scientist can reject a model he does not understand. Whether Dr. Bretscher understands the physical origins of surf-riding or not, he cannot deny that surf-riding is an observational reality. In other situations waves do cause objects to move and the movement is size dependent. Hewitt (1979) included references to some papers on the physics of wave driven motion. A reply was sent to his letter which included a brief, non-mathematical review of the physical basis for wave particle interactions but he was not willing to discus the matter further. It may be that he does not understand the physics of surf-riding but that is no ground for rejecting the wave model. In any case, he has no apparent desire to acquire such insight. What has really been absent from the "fray" has been any reply to the wave model from men such as Dr. Bretscher. His lack of understanding seems to be a choice and one that raises questions about his ability to discharge competently the influential roles to which he has been appointed.
Fourthly, he suggests that reporting three as two is a matter of "personality." No doubt there are personality types associated with a tendency to falsify or mislead but that has nothing to do with whether a given statement is true or false. A scientific paper is written with absolutely clear, albeit implicit, assurances by the author that what is written is true. It is common sense that three is three and two is two, whatever the personality of the scientist concerned. If Dr. Bretscher reviewed this field with the words, "two possibilities have been put forward," then that is false. If he chooses instead words such as, "two possible mechanisms are widely considered," then this is true but has the same impact as the falsehood. This kind of "truth" is no different from falsehood, it is truth phrased in a way that tends to mislead and is misrepresentation by omission. In this field false and misrepresentative phraseology has become the commonplace. Dr. Bretscher's reviews create a clear and obvious gap that he declines to fill.
The whole situation has serious implications both for this field and also for quality appraisal generally. Dr. Bretscher's ideas are demonstrably wrong and even when they were published had a feeble prima facie case to support them. Even so, by citation analysis, his work is a classic and therefore appraised as being of very high quality. By contrast, the wave model, which is almost certainly correct, is little cited and therefore appraised as being of low quality, with all the expected sequelae arising from decisions in scientific management. At the same time Dr. Bretscher, and other authors of this misrepresentation, repudiate the need explain the rejection of the alternative theory and fail to do so, even when directly asked.
Extensive studies of capping have been carried out in the USA as well as Britain. Almost all of what little recognition the wave model has enjoyed, in the form of acknowledgement in the literature, has been from American workers, indeed there has been positive support from those shores.
Today however, the leading American workers seem again to be taking their lead from their British colleagues, with almost nothing in the way of explanation being available in the literature. There is nothing to indicate why this should be so. American authors have recently published two sets of particularly seminal papers in the Journals Nature and Science which this chapter will review. The striking thing about these influential articles is that they claim to establish the correctness of the cytoskeletal model by disproving the membrane flow model. This, of course, presents a problem - how was the wave model eliminated? The workers involved were asked to explain the reasoning leading to their rejection of this alternative.
Sheetz and coworkers, now of Duke University, published his work in Nature (Kucik, Elson & Sheetz (1989), Sheetz et al. (1989)). Nature gave Dr. Bretscher the space to respond to these papers, presumably because they were seen as being critical of his work. Advocates of the wave model received no such facility, though it is from that standpoint that constructive criticism could have been offered. The experiments are elegant, in themselves, and executed with impressive technology, while the observations are clear and do seem to disprove the flow model. The objection to these papers is the selectivity of the discussion about possible mechanisms, especially considering the detail of their observations. This very series of papers provides some of the best supportive evidence for the wave model, for example the particles changing direction and, in a parallel paper in The Journal of Cell Biology (Kucik et al. (1990)) the observations of "dramatic waves" moving "in concert" with particles.
Reversals of motion cannot obviously be described with the cytoskeletal flow model these workers advocate and their observations seem difficult to account for except with the wave model. Their data seem clearly supportive of the wave model yet, in their Nature papers, whose purpose is to discuss the mechanism of capping, they neither draw attention to their observations of waves, nor even mention the possibility that they are observing wave driving.
Prof. Sheetz's was asked for his views on the wave model. In his reply (archived in the internet site), he advised that "we feel there is ample evidence that rearward migration ..... does not necessarily involve a wave" and mentioned The Journal of Cell Biology paper describing "dramatic waves" whose movement "correlates" with the movement of particles. Despite the observations it reports and his reference to it, the article does not even mention, let alone discuss, the wave model.
He states in his letter that he has no doubt they would observe a wave motion, if it existed, on their subject cells, "we can indeed see other undulations on that surface". This commentary is difficult to interpret, since the dictionary definition of undulation is, "a wave like motion." What is more, in their paper these workers say they can see dramatic waves. Prof. Sheetz should describe these observations in more detail. As it is, he does not indicate what there is about his observations to contradict the wave model and, beyond this somewhat ambiguous commentary, he does not respond to letters.
His letter adds the claim that studies of myosin mutants mentioned in section 7.8 in dictyostelium are inconsistent with the wave model. Unfortunately he did not refer to any particular paper and seems to be unwilling to elaborate further. In fact, the dictyostelium studies seem supportive of the wave model.
His letter and papers leave several unanswered questions; what are the properties of the undulations or "dramatic waves" he reports observing but which he has not characterised in detail? What is the statistical incidence of oscillatory behaviour or stop start motion in the particles they observe? What precisely is there about his own work or the dictyostelium studies he believes to contradict the wave model? Prof. Sheetz should place on the scientific record, both the fact that he rejects the wave model and his reasoning. Only in this way can these matters be the subject of constructive debate.
Jacobsen's group at the University of North Carolina published their work in the journal Science, Lee et al. (1990)). These papers, again, clearly and elegantly exclude the membrane flow models. Again, the wave model is simply ignored. Again, the cytoskeletal (flow) model is found to be correct simply by elimination of the membrane flow model. Science, like Nature before it, carried an exchange of views with Bretscher, who puts his side of the case. Again, no space was given to any advocate of the wave model.
Letters were written to Prof. Jacobsen who did indicate an intention to reply. However, no further correspondence has been received from him. It seems that Prof. Jacobsen does not really intend to reply to questions.
In scientific content, these replies mean nothing at all. The letters are, initially, normally polite, even overtly upbeat. What is wrong with them, is that they are scrupulous in their evasion of the questions being asked. These are scientists who have taken a professional position rejecting the wave model or consciously ignoring it. That is obvious to anyone in the field. To enquiries about how they came to this professional conclusion, some scientists don't reply, others offer replies that contain no meaning, then offer excuses (or exasperation) when asked to reply properly.
If a scientist wishes to express the opinion that the wave model is wrong he only has to write, "I think the wave model is wrong." It is true that if he did this on record he would be subject to the discipline of explaining how he came to his view but that is not a bad thing. A reluctance to give reasons for an opinion, raises doubts about the validity of the opinion. There is a professional duty to clarify matters such as this but in terms of real meaning nothing is discernible but a wall of silence. There have been at least three models of capping and particle movement. Reporting that there are two is not the expression of an opinion, it is a falsehood achieved by omission. The falsehood might be remedied if the gaps were filled when the rationale was asked for but that has not happened. To this group of scientists falsehood by omission seems acceptable. This is evidently scientific debate aimed at discerning truth. Scientifically, both their papers and letters mean nothing and it might be suspected that nothing is what they are intended to mean. Nothing, cannot be replied to. Nothing cannot be rebutted.
Nothing, disregard, may be a convenient tactic for those with administrative power but it is also bad science and falsehood is unprofessional behaviour. However, this individual opinion is of less immediate relevance than the views of the institutions that nurture the work of such men. Accordingly contacts were made with the institutions concerned and are the subject of the next chapter.
This Chapter has :-
- Reported that a number of well qualified, serious scientists have advocated the wave model as correct.
- Stated that most "establishment" figures, the gatekeepers of the field, have disregarded the wave model.
- Named representative figures who appear to reject the wave model and quoted from their replies when the issues are put to them.
- Pointed out that these replies amount to nothing but a wall of silence.
© Copyright John A Hewitt.
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Last Modified 1 June 2004