Systems biology and multilevel causation
Systems biology treats an organism as a multifactorial system in which changes at the molecular level are frequently buffered before they reach the higher phenotype levels5. Noble argued that biology must create order from stochastic processes at the lower level6. The idea matters because it bears on how gene function is inferred and how regulatory models are built78.
- Earliest held
- 1915, Bayliss, W. M.
- Most discussed in
- Biophysics and systems biology, 2010
- In the library
- 165 passages in 77 works
- Rewritten
- 2026-10-13
Chemical buffers
The word buffer entered physiology as a chemical term. Bayliss (1915) described how bicarbonates, phosphates and aminoacids soak up excess hydrogen or hydroxyl ions, and traced the name from Fernbach and Hubert's "tampons" through Sorensen to the German Puffer and the English Buffer1. He thought the word poor, since a railway buffer does not absorb the engine as these substances absorb ions, and a sponge would suggest the meaning better1. Hill (1926) argued that the buffers of muscle must be as effective as those of the blood and far greater in total amount4.
Buffering and regulation
Authors of the 1910s drew different conclusions from buffering. Loeb (1916) cited L. Henderson on the fitness of the environment, with buffers in sea water and blood as one element of it2. He held that such quantitative laws leave no room for a directing force of the vitalist2. Haldane (1917) agreed that Henderson's point was true and important. He added that the disturbances physiology deals with are far more minute than chemical methods can detect, so exact regulation of blood reaction remained indispensable3.
Noble on buffered systems
Noble (2010) held that molecular changes can have large effects at higher phenotype levels, but that these effects are frequently buffered5. He gave sodium channel mutations, which do not by themselves trigger cardiac arrhythmia5. He cited Auffray and colleagues and Kupiec in arguing that biology creates order from stochastic processes, and that no biological system escapes Brownian stochasticity6. He proposed that computational models extending to gene products could estimate each product's contribution, even where the system buffers a knockout completely7. He agreed the field was far from doing this in general7.
Network inference and design
Later work turns the multilevel picture into methods. Lobo and Levin (2015) inferred regulatory networks from planarian regeneration experiments and described the result as a systems-biology dynamical model of patterning8. They presented the method as a general framework for identifying control mechanisms behind the regulation of growth and form8. Pla-Mauri and Solé (2026) noted that theoretical systems biology has shown cell-signalling networks can generate context-dependent dynamic behaviour.
A railway buffer does not absorb the engine itself, as the substances referred to absorb ions. A word more suggestive of a sponge would probably be better, but is not easy to find.
Bayliss, W. M., 1915 · Principles of General Physiology · open at passage 907These buffers are the carbonates and phosphates. Instead of saying that the organisms are adapted to the medium, L. Henderson has pointed out the fitness of the environment for the development of organisms
Loeb, J., 1916 · The Organism as a Whole, from a Physicochemical Viewpoint · open at passage 482but the disturbances which physiology has to deal with are far more minute than those which are appreciable by chemical methods, so that exact regulation of the reaction of the blood is indispensable.
Haldane, J. S., 1917 · Organism and Environment as Illustrated by the Physiology of Breathing · open at passage 75The buffers of muscle, fulfilling the same function, must be just as effective as, and their total amount far greater than, those of the blood.
Hill, A. V., 1926 · Muscular Activity · open at passage 173So, while it is true to say that changes at the molecular level can sometimes have large effects at the higher phenotype levels, these effects are frequently buffered.
Noble D, 2010 · Biophysics and systems biology · open at passage 20There is absolutely no way in which biological systems could be immune from the stochasticity that is inherent in Brownian motion itself.
Noble D, 2010 · Biophysics and systems biology · open at passage 20That may be possible even if the system completely buffers the mutation or knockout so that no effect is observed in the phenotype.
Noble D, 2010 · Biophysics and systems biology · open at passage 44This method provides an automated, highly generalizable framework for identifying the underlying control mechanisms responsible for the dynamic regulation of growth and form.
Lobo D, Levin M, 2015 · Inferring regulatory networks from experimental morphological phenotypes: a… · open at passage 1Theoretical research in systems biology has demonstrated that biochemical networks involved in cell signaling can generate context-dependent dynamic behaviors.
Pla-Mauri J, Solé R, 2026 · Engineering Basal Cognition: Minimal Genetic Circuits for Habituation… · open at passage 74