Discussion Forum: How Dogma Hinders the Advancement of Basic Research

from Dissemination of Research

           There is so much interesting aspects to the field of immunology in addition to the amazing research it offers, including historical and societal issues, that perhaps if discussed candidly would increase the public’s support and value towards basic research.  In addition to writing and discussing the latest published research in the fields of immunology, disease and human health, I would like to experiment with a few other forums to present on Escaping Anergy.  This is the first installment of Discussion Forum devoted to enhancing our ability to discuss immunology in an open, philosophical, communicative way.  After all…

Immunology is complicated.  It’s like a giant puzzle without a box depicting how the picture is supposed to look.  It becomes further complicated, because every few years a new puzzle piece drops into the pile.  The thing is, sometimes it feels as Sometimes that new piece in the “missing link” that can unify part of the puzzle, and other times it can’t seem to fit into the existing puzzle.  In research, the puzzle, in its entirety, is never complete, but people are working towards completing smaller chunks of the puzzle that can explain major biological processes.  Dogma represents a big chunk of the puzzle completed, but that can’t incorporate the remaining puzzle pieces.  It is much easier to accept the idea that at least a portion of the puzzle is completed, than to  re-examine the puzzle to ensure that the all the pieces in the completed section fit together smoothly and not forced into curves.   Fortunately, there are a number of scientists and educators who never lost their ability to question and whose curiosity has not waned. 

            Taking a few moments to describe how current dogmas evolve, one can begin to appreciate the challenges scientists encounter when trying to understand biological phenomena.  For example, in my specific field, macrophage biology, the dogma describing the function of these cells, has been under constant revision since their discovery at the turn of the 20^th century. In the late 1890’s, Elie Metchnikoff (the “Father of Natural Immunity”) first described these cells merely based on what he could physically see: big tissue cells that were able to rapidly engulf dead cells.  For these reasons, he aptly called them “macrophages”. ¹ Over the next 60 years, scientists around the world wanted to know more about what role these “big eaters” have in the immune system.  In the mid-20^th century, a sentinel experiment by Mackaness and colleagues was performed using bacteria-infected macrophages. ² In these experiments, they analyzed what the macrophages produced during infection and discovered that not only were these cells very good at eating and destroying bacteria, but produced huge amounts of pro-inflammatory cytokines as well.  These cytokines, TNFalpha and IL-12, are crucial mediators of the adaptive immune response and cellular recruitment to the site of infection.  This inflammatory, anti-microbial phenotype was then used to describe macrophage function for nearly 50 years.   Immunologists were largely content with relying on this new dogma of "classical macrophage activation".   This compelling description of macrophage function seemed to be etched into stone for decades, being unequivocally taught to future immunologists and so on.   It would be nearly half a century would pass before anyone proposed the notion of "alternatively activated macrophages".  This, to me, seems a bit surprising, after all in a field where people are trained to question their surroundings, be curious and ask questions, the idea of accepting dogma and moving on, should struggle to persist.   
             Before the millennium was over, numerous groups had discovered alternative activation macrophage states, including macrophages that were exactly the opposite of Mackaness’ classical macrophages.  Siamon Gordon, David Mosser and others discovered all sorts of abilities macrophages possessed that were previously thought of as impossible.  They had described macrophages that although were still very good at phagocytosis, were not able to control microbial infections and macrophages that were potent anti-inflammatory cytokine producers playing a significant role in regulating inflammation.^3,4   Finally, we are beginning to appreciate that our previous understanding of macrophage function was over simplified and restricted; in fact we know believe there is a whole spectrum of macrophage diversity to explain how these cells work, behave and modulate immune responses.  It turns out that macrophage are capable of behaving in so many different ways depending on what they sense in their environment, and when and under what conditions.   However what factors regulate macrophage function and how and importantly, what other functions are these cells able to perform remain incomplete and elusive.  It is stunning to imagine what discoveries could have been made sooner if not for the 50-year lag in providing evidence for such an array macrophage activation states.  It is now known that such alternatively activated macrophages play significant roles in tumor development, microbial susceptibility, intestinal homeostasis and wound healing!

I believe that it is this fast-paced, dramatic evolution of understanding that provides the mystique that attracts people to the field, while simultaneously representing a major driving force to discourage people from taking an interest in research. However, the puzzle of understanding biological depends on the public’s support of basic research, which tackles essential questions that must be answered or expanded upon, in order to fully understand the mechanism behind disease.

As a doctorate student, I am supposed to devote most of my waking (and often, dreaming) hours to my research thesis, if I ever hope to successfully complete my PhD and move on to future endeavors.  Although, my time in the lab consumes 95-98% of the hours in a week, I desperately savor a few hours each week to “break” from the bench and take time to learn something new about immunology.  I treasure this time because, with all my course-work completed, I still yearn to learn new things.  I use this time to stay current with new discoveries and ideas and to further educate myself in immunology.  The time I spend reading the latest published research reminds me why I began investigating scientific research as a career in the first place: to always be in a position to challenge myself to learn new things. The field of immunological research is very challenging largely, because what we [think] we know about it is always morphing and expanding, new discoveries are always being made, and models of understanding are always in revision.

I understand this is exactly the aspect of science that often discourages people from wanting to learn more about it or why so many educators resort to using test-books that lump together decades of research to create main bullet points of understanding for students to memorize as facts.  But I think if we want to advance our scientific understanding of disease, we must be able to effectively and openly discuss how new research findings supports or changes current understanding.  

All children are curious beings, constantly trying to figure out the world around them and how it works.  Somewhere along the path to adulthood most of us, abandon our ability to do this.  We figure it’s easier to live in a world where other people figure things out; after-all our lives have become increasingly more hectic since we were kids.  For science to work the way we want it to-by providing insight into how our bodies work so that we can cure, prevent, and effectively treat diseases, all of us-scientists and non-scientists-must continue to think creatively and intelligently about the amazing physiological phenomena our bodies encounter everyday.  

Biological research is a very challenging field with limited immediate satisfaction.  These qualities tend to push the vast majority of would-be scientists away from the realm of research.  By assuming our current understanding of immunology is static and somehow set in stone, the field is doomed to lend itself in the development of drugs and treatments that work effectively and properly to treat disease.  

Whether you are also a young scientist, or an older one, or someone who just wants to make more time in their busy life to learn something new, or a concerned citizen who wants to understand how their tax dollars lead to scientific advancement, I encourage you to ask more questions and to never take the easy route to scientific understanding!  Thanks for reading and I hope our discussion continues!

What makes you want to understand immunology and support the research behind it?

What motivates you to continue to be curious about science? 

Please feel free to comment below or shoot me an e-mail to discuss the philosophy of immunological research!

Mosser, D., & Edwards, J. (2008). Exploring the full spectrum of macrophage activation Nature Reviews Immunology, 8 (12), 958-969 DOI: 10.1038/nri2448






References and Further Reading:

1: Metschnikoff, E. Biol. Zentralblatt 3: 560–565 (1883).

2: Mackaness, G. B. "The immunological basis of acquired cellular resistance. "J. Exp. Med. 120:105-120(1964).

3: Stein, M., Keshav, S., Harris, N. & Gordon, S. “Interleukin 4 potently enhances murine macrophage mannose receptor activity: a marker of alternative immunologic macrophage activation”. J. Exp. Med. 176: 287–292 (1992).

4: Mosser, D. and Edwards, J. “Exploring the full spectrum of macrophage activation”. Nature Reviews Immunology. 8:958-969. (2008).