Shifting our mindset back to the basics.

As this is a forum for learning and discovery, I wanted to stay away from any form of writing that might come across as a rant.  But perhaps you will permit me, this one time, to go off on a slight tangent.  Some of this article has appeared in Queen’s Health Science Journal, volume 13, 2013.

I was inspired but a recent editorial by Bob MacDonald, a well-known, well-liked Canadian science journalist who works for the Canadian Broadcast Corporation.  In his editorial (check it out here), he argues for increased funding for the basic sciences.  The trend across many countries involves funneling research dollars away from basic research to those projects most likely to have direct impact on its citizens and/or on economic growth.  Quite frankly, this trend is short-sited.  As MacDonald writes, “To focus only on applied sciences is to limit future possibilities”¹. 

You might wonder how this affects cancer research? Isn’t it all cancer research mostly more or less applied? In theory, the answer is yes.  And some cancer research is directly applicable such as clinical trials.  But there are also a large yet essential number of us that work far away from the patient bedside.  Our work is critical.  Imagine your physician sequences your cancer genome and finds a mutation in gene A.  What is the function of gene A?  Can we develop a therapy to specifically target this gene?  What happens to gene B, C, or X? What are the possible side effects?  This is where basic cancer research comes into play.  At its simplest, cancer is the disruption of normal physiology.  Therefore, in order to understand this disease, we need to understand normal cellular and molecular biology.

Taking a step even further back into basic experimental science, a certain element of curiosity remains indispensable.  Let’s look back into history, to a time when scientists could delve into scientific problems merely to ease their inquiring minds.  How many discoveries made within that mindset have since proven essential for understanding human diseases today?  Of course, Dr. Fleming’s discovery of penicillin in 1928 is the obvious example of how accidental discoveries and open-mindedness have the potential to impact the broader society for years to come. 

Other, perhaps less evident examples includes both Peyton Rous’ hypothesis of environmental factors as cancer-causing entities as well as the characterization of the cell cycle components by Sir Paul Nurse and his colleagues.  In the early 20^th century, Peyton Rous – at a time when he wasn’t particularly interested in cancer – took non-cellular material from a hen with cancer, injected it into healthy birds, and observed the subsequent development of sarcomas.  At that time, the scientific community would not easily accept his idea that non-genetic factors such as environmental stimulus or viral components could promote tumorigenesis².  Now, in the 21^st century, this idea provides the foundation behind the etiology of many specific cancers.  More specifically, smoking is now regarded as the leading cause of lung cancer³ and infection with the human papilloma virus is considered the central etiological factor contributing to the development of cervical cancer in women⁴.  

The identification of the cell cycle and its components is another example of how basic biology research can provide fundamental knowledge for disease prevention and treatment.  In 2001, Paul Nurse, Leland Hartwell, and Tim Hunt were awarded the Nobel Prize in Physiology or Medicine for their collective discoveries of key regulators of the cell cycle more than 30 years earlier (including the discovery of cell division cycle genes (CDCs) and cyclins).  In a telephone interview for a scientific journal, Paul Nurse describes his motivating factor as “curiosity coupled with coming up with good explanations for scientific problems”⁵.  In the 1960’s and 1970’s, understanding the cell cycle was interesting simply for its role in mediating basic biologic functions, without awareness of its foundational aspect in pathology.   Now, of course, we realize how the cell cycle is intricately coupled to many disease states including cancer, cardiovascular, and autoimmune diseases⁶.

These examples illustrate how research elicited for the pursuit of scientific knowledge will, over time, prove to be useful – even essential – to our current understanding of disease and its treatments.  Unfortunately, the current funding landscapes demand more and more utilitarian outputs and a direct translation of basic research for clinical benefit⁷.  Thus, not only does the competitive scientific environment insist on a quantity of publications, but the funding landscape now also prescribes what researchers should be studying and publishing.  This prescription is doomed for disaster.

Perhaps I’m preaching to the choir.  I have a feeling I’m not.  I have a feeling there’s enough people out there who think that research should lead directly to a useful output.  I argue that we, and our government, need to rethink this mindset.  Please.

References

(1) MacDonald B. Scientists urge government to fund basic research.  http://www.cbc.ca/news/technology/scientists-urge-government-to-fund-basic-research-1.2756038

(2) Simmons J. Doctors and discoveries : lives that created today's medicine /. Boston: Houghton Mifflin; 2002.

(3) Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013;143: e1S-29S.

(4) Bosch FX, Manos MM, Munoz N, Sherman M, Jansen AM, Peto J, et al. Prevalence of human papillomavirus in cervical cancer: a worldwide perspective. International biological study on cervical cancer (IBSCC) Study Group. J Natl Cancer Inst 1995;87: 796-802.

(5) Nurse P. The cell cycle and beyond: an interview with Paul Nurse. Interview by Jim Smith. Dis Model Mech 2009;2: 113-115.

(6) Zhivotovsky B, Orrenius S. Cell cycle and cell death in disease: past, present and future. J Intern Med 2010;268: 395-409.

(7) Botstein D. Why we need more basic biology research, not less. Mol Biol Cell 2012;23: 4160-4161.