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The Disregard Syndrome: A Menace to Honest Science?

We are witnessing the continuation of an accelerated, unprecedented explosion of scientific information that might make the life of a serious investigator unbearably complicated. Unlike our pioneering investigators, however, we are fortunate to have access to modern information-retrieving pools such as Medline, Biological Abstracts, and more recently selected electronic journals. These allow us, at the press of a key, to choose desired scientific citations. A search for articles in the medical

By | December 10, 2001

We are witnessing the continuation of an accelerated, unprecedented explosion of scientific information that might make the life of a serious investigator unbearably complicated. Unlike our pioneering investigators, however, we are fortunate to have access to modern information-retrieving pools such as Medline, Biological Abstracts, and more recently selected electronic journals. These allow us, at the press of a key, to choose desired scientific citations.

A search for articles in the medical and biological sciences published in the pre-Medline era necessitates browsing through the heavy volumes of Index Medicus. The invaluable wealth of the "old" scientific observations stored in these volumes was painstakingly obtained by those pioneers due to their ingenuity and perspicacity. Despite their lack of access to any of the modern technologies, they still managed to elucidate, in great depth, indispensable basic biological and biochemical phenomena that, if ignored, could greatly diminish our abilities to evaluate the present status of modern research.

It might have been expected that a careful literature search--in Index Medicus, Medline, Biological Abstracts, or in the electronic journals--would guarantee that a lack of regard for already published data would not occur and that authors would also consider with respect all viewpoints expressed. But it transpires that mainly because of the information overload of scientific publications, expert referees nominated by journal editorial boards are unable to cover the vast literature to prevent duplications of already published data. This might well provide a haven for redundant scientific information.

Can we identify the main roots and motivations behind the unethical and self-defeating "disregard syndrome," discussed in 1991 by Eugene Garfield, founder of The Scientist?1 [Columbia University sociologist Robert K Merton also called it "citation amnesia."] Can we prescribe a prophylactic or an antidote and means for its application? Also, can one guarantee that reliance solely on computer database abstracts, without the reading of the full texts of articles and a thorough scrutiny of the lists of references cited by authors, might not lead to acceptance for publication of previously performed research, not to mention a waste of precious public funding and journal space. There is a growing concern that the disregard syndrome has already contributed to the disappearance of whole lines of research from the awareness of investigators.

Over the years, in my own field, I have identified at least three main types of disregard syndromes:

  • Unintentional failure to cite previously published pioneering works due either to oversight, negligence, or to the assumption that "old" nonmolecular and nongenetically oriented data are, today, not considered a "cutting edge of modern science."
  • An apparently intentional disregard for already published data that do not seem to conform to dogmas adopted by certain investigators.
  • An unintentional lack of regard for relevant literature due to ignorance of a change of nomenclature.

Whenever I have been convinced that key citations relevant to the topic were ignored, I have contacted the authors and sometimes journal editors. Besides raising the "disregard issue," the message listed those "missing" citations that to the best of my judgment should have been included. I asked the corresponding author to explain why he had disregarded relevant pioneering publications. This tactic has produced more than a dozen responses, and since 1999, resulted in publication of five letters to the editor.

As to unintentional failure to cite, following are anecdotal examples of the explanations presented when authors did respond: I do not read those journals ... Restrictions on space allocated by the journal prevented extensive coverage of the literature ... I had difficulties [retrieving] older papers from University libraries ... Citations are included only if cited by others ... I am a newcomer to this field of research and, therefore, not knowledgeable of the older literature.

As to intentional disregard, two parallel lines of research have been conducted to elucidate the mechanisms by which leukocyte-derived-basically-charged proteins kill microorganisms. Debate centers around host mechanisms of innate immunity to infections. One trend has proposed that the highly basic-charged agents, released by leukocytes, interact with negatively charged domains present upon the bacterial surface to enhance its permeability, resulting in cell killing.2 An alternative line of research has proposed that, similarly to the antibiotic penicillin, highly basically-charged proteins might also kill bacteria by functioning as Trojan horses capable of activating endogenous enzymes, named muramidases (cell-wall breaking enzymes), to induce a suicidal bacteriolysis and cell death.3 It is an enigma why publications proposing the bacteriolysis-inducing activities of basic proteins are never cited in any of the numerous publications by those groups of authors who have proposed the permeability-enhancing phenomenon as the main cause of bacterial death induced by basically-charged proteins.

Also today, although there is a consensus that tissue injury induced in inflammation, infection, and in post-infectious manifestation is multifactorial, there still is a reductionism approach to report on the role in tissue damage of only one single pro-inflammatory agent. However, already in 1960 and more extensively since 1987, it has been proposed that many of the pro-inflammatory agents generated in vivo might mainly act in synergy, a topic extensively reviewed.4 It is not clear why, today, publications that propose the synergism concept of cell injury are hardly cited in any of the numerous publications that address the mechanisms of tissue damage in inflammation and infection.

As to unintentional disregard, already in the early 1950s, a series of pioneering publications described the presence in cultures from various bacterial species of an agent named a cell-sensitizing factor (SF), which is capable of spontaneously binding to mammalian cells. Such sensitized cells can be destroyed by plasma of patients possessing antibacterial antibodies--a "passive immune kill phenomenon."5 In 1975, the chemical structure of SF was identified and renamed "lipoteichoic acid" (LTA).6 Since the introduction of the new nomenclature, the pioneering papers on SF have rarely been cited in the vast literature on LTA (more than 200 publications). A simple inclusion of a sentence that today's LTA was previously termed SF might have sufficed to alert the reader to the existence of pioneering and indispensable publications on the subject.

Who is to be blamed for allowing authors to disregard pioneering and pivotal publications? Should one point a finger at the author, referees, or the editorial boards? Is there also today a dominant trend of thought that older scientific discoveries are already passé, and that scientific data that are neither molecular nor genetically oriented are not considered in the cutting edge of advanced research? Are scientific ideas and concepts that do not seem to fit certain fashionable dogmas consistently sentenced to fade into oblivion?

I offer the following proposals for journals to consider:

  • Instruct authors and referees to ensure that the data are original and not simply rediscoveries. Every paper submitted should be required to include an introductory historical coverage of pioneering investigations on which the current research is based. If there is a strict limitation on the number of citations, adequate review articles covering the pioneering publications should be provided.
  • Nominate emeriti professors, especially those who continue their research activities, routinely as referees. There are excellent chances that elder investigators might act as true watchdogs. Furthermore, emeriti professors most probably have a much broader and integrative knowledge and approach to several contiguous fields of research. Younger investigators today tend to focus their research efforts on restricted, selective fields. They, therefore, might not be aware of events happening even in related fields.
  • Instruct authors and referees to guarantee that all scientific viewpoints be equally respected by authors irrespective of the possibility that these might not always fully conform with their own dogmas and beliefs. We hope that the days when ideas could be intentionally suppressed are gone forever.
  • Establish a Letters to the Editor section, in which authors can specifically launch their complaints and grievances.

Finally, this is a call to the scientific communities at large, to comment on this message and also to offer additional operative suggestions on how the disregard syndrome can be fought.

Isaac Ginsburg, MSc, PhD (ginsburg@cc.huji.ac.il), is emeritus professor of microbiology, department of oral biology, Hebrew University--Hadassah, faculty of dental medicine, Jerusalem, Israel.
References
1.E. Garfield, "Bibliographic negligence: A serious transgression," The Scientist, 5[23]:14, Nov. 25, 1991.

2. P. Elsbach, "The bactericidal/permeability-increasing protein (BPI) in antibacterial defense," Journal of Leukemia Biology, 64:14-8, 1999.

3. I. Ginsburg, "The biochemistry of bacteriolysis: Facts, paradoxes, and myths," Microbiological Sciences, 5:137-42, 1988.

4. I. Ginsburg, R. Kohen, "Cell damage in inflammatory and infectious sites might involve a coordinated 'cross-talk' among oxidants, microbial hemolysins, and amphiphiles, cationic proteins, phospholipases, fatty acids, proteinases and cytokines (an overview)," Free Radical Research, 22:489-517, 1995.

5. T. Dishon et al., "Cell-sensitizing products of streptococci," Immunology, 13:555-67, 1967.

6. A.J. Wicken, K.W. Knox, "Lipoteichoic acid: a new class of bacterial antigen," Science, 187:1161- 1167, 1975.
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