Since the Principle of Biological Relativity was formulated and developed there have been many implementations in a wide range of biological fields. The purpose of this article is to assess the status of the applications of the principle and to clarify some misunderstandings. The principle requires circular causality between levels of organization. But the forms of causality are also necessarily different. They contribute in asymmetric ways. Upward causation can be represented by the differential or similar equations describing the mechanics of lower level processes. Downward causation is then best represented as determining initial and boundary conditions. The questions tackled in this article are: (1) where and when do these boundaries exist? and (2) how do they convey the influences between levels? We show that not all boundary conditions arise from higher-level organization. It is important to distinguish those that do from those that don’t. Both forms play functional roles in organisms, particularly in their responses to novel challenges. The forms of causation also change according to the levels concerned. These principles are illustrated with specific examples.

Choice in the behavior of organisms involves novelty, which may be unpredictable. Yet in retrospect, we can usually provide a rationale for the choice. A deterministic view of life cannot explain this. The solution to this paradox is that organisms can harness stochasticity through which they can generate many possible solutions to environmental challenges. They must then employ a comparator to find the solution that fits the challenge. What therefore is unpredictable in prospect can become comprehensible in retrospect. Harnessing stochastic and/or chaotic processes is essential to the ability of organisms to have agency and to make choices.

The question whether evolution is blind is usually presented as a choice between no goals at all (‘the blind watchmaker’) and long-term goals which would be external to the organism, for example in the form of special creation or intelligent design. The arguments either way do not address the question whether there are short-term goals within rather than external to organisms. Organisms and their interacting populations have evolved mechanisms by which they can harness blind stochasticity and so generate rapid functional responses to environmental challenges. They can achieve this by re-organising their genomes and/or their regulatory networks. Epigenetic as well as DNA changes are involved. Evolution may have no foresight, but it is at least partially directed by organisms themselves and by the populations of which they form part. Similar arguments support partial direction in the evolution of behavior.

Life is purposefully creative in a continuous process of maintaining integrity; it adapts to counteract change. This is an ongoing, iterative process. Its actions are essentially directed to this purpose. Life exists to exist. Physiology is the study of purposeful living function. Function necessarily implies purpose. This was accepted all the way from William Harvey in the 17th century, who identified the purpose of the heart to pump blood and so feed the organs and tissues of the body, through many 19th and early 20th century examples. But late 20th century physiology was obliged to hide these ideas in shame. Teleology became the ‘lady who no physiologist could do without, but who could not be acknowledged in public.’ This emasculation of the discipline accelerated once the Central Dogma of molecular biology was formulated, and once physiology had become sidelined as concerned only with the disposable vehicle of evolution. This development has to be reversed. Even on the practical criterion of relevance to health care, gene-centrism has been a disaster, since prediction from elements to the whole system only rarely succeeds, whereas identifying whole system functions invariably makes testable predictions at an elemental level.