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One of the most powerful objections to arise A generation after Descartes’ death in 1650 came a generation later with the emergence of the philosophy of , John Locke and the British Empiricistsbrought forth a new conception of scientific knowledge that was more modest than Descartes' failed quest for certainty. The empiricists argued for experience, rather than a priori reason, as the basis for human knowledge. Locke, despite being an admirer and sought a philosophy of Descartes, was highly critical of his methodology and science more in particular was critical of his methodological skepticism, which Locke regarded as a non-starterkeeping with scientific practice.[[CiteRef::Uzgalis (2016)]][[CiteRef::Osler (1970)]]
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One specific theological criticism of Cartesian natural philosophy had to do with the Catholic sacrament of the holy Eucharist, in which bread and wine are said to be transformed into the body and blood of Christ. The dogma of the ''Real Presence'' maintained that in this sacrament, Christ is really (as opposed to metaphorically or symbolically) present in the bread and wine. Centuries earlier, the Catholic saint, Thomas Aquinas(1225-1274)had posited an Aristotelian explanation for the ''Real Presence'' which had become the accepted Catholic ''doctrine of transubstantiation''. The doctrine held that in the Eucharist, the Aristotelian substance of the bread and wine were replaced by the body and blood of Christ, while their forms (that of bread and wine) remaining unchanged. In Descartes' corpuscularism, bread and wine differed from flesh and blood because they had a different arrangement of corpuscles. There is no obvious way that one could appear as the other. The Anglican church, the state church of England following its break with the Catholic papacy in the 1530's did not accept the ''doctrine of transubstantiation''. Thus Cartesianism did not face objections based on it, and became accepted at Cambridge University by 1680. Catholic Paris didn't accept it until 1700. Many solutions reconciling Cartesianism and the ''Real Presence'' had, by then, been proposed. Barseghyan speculates that the one accepted by the Parisian community was that proposed by Antoine Arnauld(1612-1694)in 1671, in which Christ's presence in the Eucharist was due to a miracle beyond human comprehension, and outside the ordinary course of nature described by Cartesianism.[[CiteRef::Barseghyan (2015)|p. 194]]
Another sort of objection was raised by critics more sympathetic to Descartes' theories; Antoine Arnauld and Marin Mersenne. It had to do with Descartes demonstration of the existence of God, which is the linchpin of his method. Descartes claims that our belief in the reliability of the clear and distinct perceptions of the human intellect depends on our knowledge of the existence of God as the source of that capacity. But how that knowledge be established in the first place. If we answer that we can prove God's existence from premises we clearly and distinctly perceive, then the argument collapses into circularity. Since Descartes' argument that is is possible for us to have scientific knowledge of the world fails with it, since it depends on God to underwrite the reliability of our senses and intellect. This criticism, called the '''Cartesian Circle''' has , was never been successfully countered. Within a generation, Descartes quest for certainty in scientific knowledge was widely recognized to have failed. [[CiteRef::Cottingham (1992)]][[CiteRef::Ostler (1970)]]
Critics in Decartes' era were also concerned that corpuscular explanation involved hypothetical unobservable entities, and the supposition that this invisibly small world could be understood by analogy with larger objects. Descartes countered that "there is nothing more in keeping with reason that we judge about those things that we do not perceive, because of their small size, by comparison and contrast with those that we see" [[CiteRef::Clarke (1992)|p. 267]] He felt that a plausible model, though potentially incorrect due to the unobservability of its fundamental parts, was better than none at all. The role of unobservably small entities in the physical sciences was to remain a matter of prolonged debate. In modern science, it is an accepted and central practice.
Another notable objection came from Princess Elizabeth of Bohemia (1618-1680), who questioned Descartes’ theory of substance in a letter dated the tenth of May, 1643. In it, she asks “Given that the soul of a human being is only a thinking substance, how can it affect the bodily spirits, in order to bring about voluntary actions?”[[CiteRef::Descartes (2009)]] Descartes would never gives a satisfactory answer to this central question over the course of the correspondence. In 1747, in his ''L'Homme machine''(''Machine Man'') Julien Offray de La Mettrie (1709-1751) raised another simple, but devastating objection to Descartes' supposition that human reason must be due to an immaterial mental substance. He noted that reason can become impaired by material causes such as drunkenness and fever. [[CiteRef::De La Mettrie (1996)]]. In the nineteenth century, Princess Elizabeth's objection became far more poignant with the formulation of the law of the conservation of energy, which implied causal closure of the physical world to influence by a mental substance. In the early twentieth century, the mathematician Alan Turing (1912-1954) showed that it was possible to construct a general purpose machine capable of performing any possible mathematical computation, thereby demonstrating that a general purpose machine was possible and refuting Descartes' core argument against a mechanical understanding of human reason. By the end of the twentieth century, the relevant scientific communities of neuroscience and cognitive science had rejected the idea of a mental substance and sought a mechanistic physical explanation for the mind [[CiteRef::Bechtel (2008)]], though there was still no agreement as to whether consciousness could be explained in this fashion. [[CiteRef::Chalmers (1996)]]
Descartes' physical natural philosophy did not fare nearly so well. Within fifty years, Issac Newton (1642-1726) formulated a more mathematically precise and explanatorily powerful physical theory, which became the accepted theory of the physical world. It rejected a major tenet of Descartes' corpuscularism by positing a gravitational force that acted at a distance. Newton's laws of motion, however, bore important similarities to those formulated earlier by Descartes. [[CiteRef::Clarke (1992)]] As practicing scientists, researchers like Newton and Robert Boyle (1627-1691)did not, as did Descartes, seek certain knowledge of the real essences of material objects. Instead, they sought an ordering of phenomenal experience which would enable them to predict nature's course with the best available theory. [[CiteRef::Osler 1970]]
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