Ten questions about systems biology
Open accessAbstract
In this paper we raise 'ten questions' broadly related to 'omics', the term systems biology, and why the new biology has failed to deliver major therapeutic advances for many common diseases, especially diabetes and cardiovascular disease. We argue that a fundamentally narrow and reductionist perspective about the contribution of genes and genetic variants to disease is a key reason 'omics' has failed to deliver the anticipated breakthroughs. We then point out the critical utility of key concepts from physiology like homeostasis, regulated systems and redundancy as major intellectual tools to understand how whole animals adapt to the real world. We argue that a lack of fluency in these concepts is a major stumbling block for what has been narrowly defined as 'systems biology' by some of its leading advocates. We also point out that it is a failure of regulation at multiple levels that causes many common diseases. Finally, we attempt to integrate our critique of reductionism into a broader social framework about so-called translational research in specific and the root causes of common diseases in general. Throughout we offer ideas and suggestions that might be incorporated into the current biomedical environment to advance the understanding of disease through the perspective of physiology in conjunction with epidemiology as opposed to bottom-up reductionism alone.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Joyner and Pedersen argue that many common diseases arise from regulatory failure across multiple levels.
“Joyner and Pedersen (260) contend that it is a failure of regulation at multiple levels that causes many common diseases.”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [260]
They also argue that poor command of core physiological concepts hinders understanding of exercise adaptation and inactivity maladaptation.
“They further argue that a lack of fluency to use key physiological concepts (like homeostasis, regulated systems and redundancy) as major intellectual tools to understand at multiple levels how whole animals adapt to exercise and maladapt to physical inactivity.”
From Lack of Exercise Is a Major Cause of Chronic Diseases (2012) · cites this paper as [260]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
Lindström, J., Ilanne-Parikka, P., Peltonen, M., Aunola, S., Eriksson, J. G., Hemiö, K., Hämäläinen, H., Härkönen, P., Keinänen-Kiukaanniemi, S., Laakso, M., et al. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69701-8 · Cited by 1,799 · see citing works
Sequencing of 50 Human Exomes Reveals Adaptation to High Altitude
Yi, X., Liang, Y., Huerta-Sanchez, E., Jin, X., Cuo, Z. X. P., Pool, J. E., Xu, X., Jiang, H., Vinckenbosch, N., Korneliussen, T. S., et al. (2010) · Science · doi:10.1126/science.1190371 · Cited by 1,611 · cited 1× · see citing works
“Two examples include the emergence of lactase persistence in various populations and the genetic adaptations of populations to unique environmental challenges like extreme altitude (Gibson, 2007; Enattah et al. 2008; Ingram et al. 2009; Simonson et al. 2010; Yi et al. 2010).”
BackgroundRegulation of coronary blood flow during exercise
Duncker, D. J., & Bache, R. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00045.2006 · Cited by 936 · see citing works
COWLEY, A. W., LIARD, J. F., & GUYTON, A. C. (1973) · Circulation Research · doi:10.1161/01.res.32.5.564 · Cited by 593 · see citing works
Acculturation and coronary heart disease in Japanese-Americans
MARMOT, M. G., & SYME, S. L. (1976) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a112296 · Cited by 564 · see citing works
Status Syndrome: A Challenge to Medicine
Marmot, M. G. (2006) · JAMA · doi:10.1001/jama.295.11.1304 · Cited by 372 · see citing works
Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy.
Rizza, R. A. (2010) · Diabetes · doi:10.2337/db10-1032 · Cited by 367 · see citing works
Association between a literature-based genetic risk score and cardiovascular events in women
Paynter, N. P. (2010) · JAMA · doi:10.1001/jama.2010.119 · Cited by 361 · see citing works
Ten Years of Life: Is It a Matter of Choice?
Fraser, G. E., & Shavlik, D. J. (2001) · Archives of Internal Medicine · doi:10.1001/archinte.161.13.1645 · Cited by 237 · see citing works
The fundamental drivers of the obesity epidemic
James, W. P. T. (2008) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00432.x · Cited by 179 · see citing works
Systems biology and integrative physiological modelling
Hester, R. L., Iliescu, R., Summers, R., & Coleman, T. G. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2010.201558 · Cited by 58 · see citing works
The nutrition transition in Cuba in the nineties: an overview
Rodríguez-Ojea, A., Jiménez, S., Berdasco, A., & Esquivel, M. (2002) · Public Health Nutrition · doi:10.1079/phn2001284 · Cited by 47 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lack of Exercise Is a Major Cause of Chronic Diseases
Booth, F. W., Roberts, C. K., & Laye, M. J. (2012) · Comprehensive Physiology · doi:10.1002/cphy.c110025 · Cited by 2,575 · see citing works
Role of Inactivity in Chronic Diseases: Evolutionary Insight and Pathophysiological Mechanisms
Booth, F. W., Roberts, C. K., Thyfault, J. P., Ruegsegger, G. N., & Toedebusch, R. G. (2017) · Physiological Reviews · doi:10.1152/physrev.00019.2016 · Cited by 696 · see citing works
The physiology of optimizing health with a focus on exercise as medicine
Pedersen, B. K. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114339 · Cited by 163 · see citing works
Self-citationTranslational Geroscience: Emphasizing function to achieve optimal longevity
Seals, D. R., & Melov, S. (2014) · Aging · doi:10.18632/aging.100694 · Cited by 90 · see citing works
Antioxidants in Personalized Nutrition and Exercise
Margaritelis, N. V., Paschalis, V., Theodorou, A. A., Kyparos, A., & Nikolaidis, M. G. (2018) · Advances in Nutrition · doi:10.1093/advances/nmy052 · Cited by 84 · see citing works
Epigenetics in comparative biology: why we should pay attention
Burggren, W. W., & Crews, D. (2014) · Integrative and Comparative Biology · doi:10.1093/icb/icu013 · Cited by 72 · see citing works
- Authors
- Joyner, M. J., & Pedersen, B. K.
- Affiliations
- Mayo Clinic (US)
- University of Copenhagen (DK)
- Corresponding author
- Joyner, Michael J.
- Venue
- The Journal of Physiology
- Publisher
- Wiley
- Published
- 2011-02-25
- Volume
- 589
- Issue
- 5
- Pages
- 1017-1030
- ISSN
- 0022-3751 (ISSN-L)
- 1469-7793
- PMC
- PMC3060582
- OpenAlex
- W1848160003
- Cited by
- 93
- References
- 13
- Citations by year
- 2024: 2 · 2023: 5 · 2022: 4 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 10 · 2017: 8 · 2016: 7 · 2015: 9 · 2014: 5 · 2013: 15 · 2012: 7
- FWCI
- 17.62
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- The Journal of Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL046493, HL-46493, HL83947, R01HL083947)
- National Center for Research Resources (RR-24150, UL1RR024150)
- Topics
- Social Sciences › Arts and Humanities › History and Philosophy of Science › Philosophy and History of Science
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Social Sciences › Decision Sciences › Information Systems and Management › Interdisciplinary Research and Collaboration
- Keywords
- systems biology, omics, reductionism, homeostasis, diabetes mellitus, cardiovascular disease, common diseases, translational research, genetic variants, disease regulation
- MeSH terms
- Animals, Genetic Variation, Polymorphism, Single Nucleotide, Systems Biology
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
