Immunology Needs A '70s Groove
Richard Gallagher, Editor, The Scientist, 17(2):15 January 2003
Turn to page 10 of this issue to view a first-rate Eureka moment, a full-blown YOOOO-REEEEEEE-KAAA epiphany: a photograph of the lab notebook page recording the discovery of the virus now known as HIV.
The document deserves prominent display in a major museum. However, when I contacted author Francoise Barré-Sinoussi to ask for it, the reply was, and I paraphrase, "I should have that somewhere, let me get back to you." Who says that researchers are all egomaniacs?
Since the discovery of HIV, known then as LAV (lymphadenopathy-associated virus), there have been many breakthroughs in understanding HIV pathogenesis and in preventing AIDS. And yet, 20 years on, researchers lack full comprehension of the virus, and treatment remains a precarious business--control rather than cure. The fallout? An ongoing human tragedy and, arguably, a blow to the standing of modern biology, particularly to immunology.
I'll ask the tough question: Has modern immunology, the poster child of biological research during the '70s and '80s and recipient of five Nobel Prizes during those years, been a story of unfulfilled promise? A damp squib even? Certainly, clinical successes--surely the acid test--have been few and far between, regardless if the goal was to develop immune-based therapies to combat allergies and autoimmune conditions, fight infectious diseases, or eliminate cancers and organ rejection problems.
Despite this, the answer is no: It is still too early to expect fail-safe new therapies. It typically takes 12 years and close to $1 billion to develop a new medicine. Moreover, the immune system is mind-numbingly complex--ask anyone who's tried to come into the field--so that, despite the incredible progress, there are still major holes in the basic understanding of immunity. It is much, much too early to write off immunology's practical benefits.
Yet something needs to be done, and now would be a good time to consider new approaches, or dust off some old ones. An intriguing example of the latter came in a recent call from Antonio Coutinho,1 who wants "... to revisit Jerne and consider the role of cellular and molecular networks in the establishment and maintenance of natural tolerance."
This refers to Niels Jerne's 1974 "immune network theory," which posits that immune responses are controlled through sets of interactions between lymphocyte antigen receptors, which stimulate and suppress responses and retain immunological memory.2
Just as the clothes, hairstyles, and music of the 1970s (the decade that taste abandoned) have been unmothballed and updated with a fresh touch,3 so too does the immune system as a network have a remarkably modern feel. With the computational and experimental tools now available, the theory is ripe for reexploration.
Perhaps other concepts from '70s immunology also could be dusted off. Remember GOD (generator of diversity), the immunological id, and self-nonself discrimination? These groovy ideas provided an intellectual framework that has yet to be adequately replaced.
2. N.K. Jerne, "Towards a network theory of the immune system." Ann Immunol, 125C:373-89, 1974.
3. For example, see Austin Powers in Goldmember.
Regarding your article on the history of immunology,1 why stop at the 1970s? Why not go back to the 1920s--Metalnikov's work on conditioned responses of the immune system, à la Pavlov, at the Pasteur Institute, and Hans Selye's initial ideas on the "syndrome of just being sick." One of the great problems in immunology research in the 20th century was its almost total domination by medical infectious disease specialists looking into clonal immunity. In some ways this is the least important role of the immune system, and one that it carries out poorly, because infectious disease epidemics usually only arise under conditions of overpopulation. It is the everyday fight against small breaches of body integrity due to trauma, etc., that prevents us from being literally eaten alive by common microorganisms that is much more fundamental.
The immune system also needs to be looked at from a total systems perspective as being part of the body's overall defense and repair mechanisms, which is why we have such phenomena as the partial suppression of pain and the immune response during heightened sympathetic arousal, as for example, when attempting to escape from a predator after being attacked. This is all ultimately controlled by the modulatory neural pathways in the brain--dopamine, norepinephrine, serotonin, acetylcholine, and histamine. Genetic variations in these pathways are also responsible for the vast majority of the psychiatric and neuropsychiatric disorders, which is where much fundamental research is being carried out, though we still have a long way to go.
There is also quite strong evidence of various sorts that at least some of the autoimmune diseases may be very closely related to these brain disorders, a good case in point being multiple sclerosis.
1. R. Gallagher, "Immunology needs a '70s groove," The Scientist, 17:15, Jan. 27, 2003.
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