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Around the age of 38, and with a remarkable academic career behind him, Malpighi decided to dedicate his free time to anatomical studies.<ref name=pinto/> Although he conducted some of his studies using vivisection and others through the dissection of corpses, his most illustrative efforts appear to have been based on the use of the microscope. Because of this work, many microscopic anatomical structures are named after Malpighi, including a skin layer (Malpighi layer) and two different Malpighian corpuscles in the kidneys and the spleen, as well as the [[Malpighian tubules]] in the excretory system of insects.
Although a Dutch spectacle maker created the compound lens and inserted it in a microscope around the turn of the 17th century, and [[Galileo]] had applied the principle of the compound lens to the making of his microscope patented in 1609, its possibilities as a microscope had remained unexploited for half a century, until [[Robert Hooke]] improved the instrument{{Citation needed|date=April 2020|reason=This is an often repeated claim; Swammerdam's and Malpighi's discoveries preceded Hooke's}}. Following this, Marcello Malpighi, Hooke, and two other early investigators associated with the Royal Society, [[Nehemiah Grew]] and [[Antoine van Leeuwenhoek]] were fortunate to have a virtually untried tool in their hands as they began their investigations.<ref name="BolamJeanne">{{cite journal|author=Bolam, Jeanne|title=The Botanical Works of Nehemiah Grew, F.R.S. (1641–1712)|journal=Notes and Records of the Royal Society of London|volume=27|issue=2 |year=1973| pages =219–231|jstor=530999 |doi=10.1098/rsnr.1973.0017 }}</ref>
In 1661, Malpighi observed capillary structures in frog lungs.<ref>{{cite book |last=Gillispie |first=Charles Coulston |authorlink=Charles Coulston Gillispie |title=The Edge of Objectivity: An Essay in the History of Scientific Ideas |year=1960 |publisher=Princeton University Press |isbn=0-691-02350-6 |url=https://archive.org/details/edgeofobjectivit00char |url-access=registration |p=[https://archive.org/details/edgeofobjectivit00char/page/72 72]}}</ref> Extrapolating to humans, he offered an explanation for how air and blood mix in the lungs.<ref name="BolamJeanne" /> Malpighi also used the microscope for his studies of the skin, kidneys, and liver. For example, after he dissected a black male, Malpighi made some groundbreaking headway into the discovery of the origin of black skin. He found that the black pigment was associated with a layer of mucus just beneath the skin.
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