This was one of my favourite speculative papers that I published while editor of Medical Hypotheses. In it; Bazar, Lee and Yun construct a good argument that the human appendix may function as an immune sentinel, sampling from gut contents as they pass from small to large bowel, and potentially raising an appropriate immune response.
This was just the kind of idea that the journal existed to get into print and circulation - where (in the days of real science) it could be subjected to analysis and testing.
This recognises that the most important 'filter' on ideas should not be publication, but the further work of peers - i.e. honest workers in the same field who are motivated by the desire to discover truth. The only valid external test comes if these peers are sufficiently convinced by the case made and sufficiently interested by the implications that they explore its real world consequences.
(Peer review, by contrast, is merely the short-term opinion of someone (or a majority of someones) - who is only very seldom a real 'peer' - about whether the idea is likely to be correct. If that was real science, then so is any bureaucracy; based on committees, opinions and votes. At least that is the ideal of peer review... In practice PR seldom rises above an indirect means of career promotion.)
I particularly liked that the authors linked their specific hypotheses about the appendix to a larger theory about reconceptualising the total immune system as an intelligent, 'cognitive', informational system.
I see it has been cited 28 times (according to Google Scholar) which, although not startling, is well above average (the modal citation average is zero):
Kimberly A.Bazar, Patrick Y.Lee, Joon Yun. An “eye” in the gut: the appendix as a sentinel sensory organ of the immune intelligence network. Medical Hypotheses. 2004; 63: 752-8.
Neural systems are the traditional model of intelligence. Their complex interconnected network of wired neurons acquires, processes, and responds to environmental cues. We propose that the immune system is a parallel system of intelligence in which the gut, including the appendix, plays a prominent role in data acquisition. The immune system is essentially a virtual unwired network of interacting cells that acquires, processes, and responds to environmental data. The data is typically acquired by antigen-presenting cells (APCs) that gather antigenic information from the environment. The APCs chemically digest large antigens and deconstruct them into smaller data packets for sampling by other cells. The gut performs the same function on a larger scale. Morsels of environmental content that enter the gut are sequentially deconstructed by physical and chemical digestion. In addition to providing nutrients, the componentized contents offer environmental data to APCs in mucosa-associated lymphoid tissues (MALT) that relay the sampled information to the immune intelligence network. In this framework, positioning of the appendix immediately after the ileocecal valve is strategic: it is ideally positioned to sample environmental data in its maximally deconstructed state after small bowel digestion. For single-celled organisms, digestion of the environment has been the primary way to sample the surroundings. Prior to the emergence of complex sensory systems such as the eye, even multi-cellular organisms may have relied heavily on digestion to acquire environmental information. While the relative value of immune intelligence has diminished since the emergence of neural intelligence, organisms still use information from both systems in integrated fashion to respond appropriately to ecologic opportunities and challenges. Appendicitis may represent a momentary maladaptation in the evolutionary transition of sensory leadership from the gut to the eye. Relationships between immune dysfunctions and cognition are explored.