Discovery of Red Blood Cells

Antoni van Leeuwenhoek
(excerpted from: M. Bessis and G. Delpech., 1981, Discovery of the Red Blood Cell with notes on priorities and credits of discoveries. Blood Cells 7:447-480)

Antoni van Leeuwenhoek is widely credited as the discoverer of red blood cells. In truth, he was not the first person to observe "red particles" in blood but his observations were more detailed and numerous than those (by Malpighi and Swammerdam) that preceded him .

1) Antoni van Leeuwenhoek (1632-1723)

Leeuwenhoek's first written description of human red blood cells (his own) was in a letter to Constantine Huygens (father of the physicist and astronomer Christiaan Huygens) on April 5, 1674 and later in another letter addressed to Mr. Oldenberg, Secretary of the Royal Society of London on April 5, 1674. The first publication of the observation of globules in blood occurred in April 1674 in the Philosophical Transactions of the Royal

Society of London in which Leeuwenhoek published his 1673 observations reported in the letter to Huygens (see Figure). In a letter dated August 14, 1675, Leeuwenhoek went on to make the remarkable discovery that "those sanguineous globules in a healthy body must be very flexible and pliant, if they are to pass through the small capillary veins and arteries, and that in their passage they change into an oval figure, reassuming their roundness when they come into a larger room."

The first known drawings of animal red blood cells by Leeuwenhoek were contained in letters dated March 3, 1682 (salmon red blood cells) and July 16, 1683 (frog red blood cells). Leeuwenhoek's first drawing of human red blood cells (long thought to be the first drawing ever of human red blood cells) was contained in a letter dated July 7, 1700. Leeuwenhoek, despite many years of study of red blood cells, continued to mistakenly view them as spheres (globules in his terminology).







Leeuwenhoek's first published observation of red blood cells, in 1674, of human blood cell

Marcello Malpighi

2) Marcello Malpighi (1628-1694)

Malpighi was a distinguished anatomist whose name has been applied to the malpighian tubules of insects (their equivalent of a kidney) and to a layer of the epidermis of the skin. Indeed, the first observation of the existence of red blood cells (from a dog) appears to have been made by Malpighi in a March 1661 letter to Borelli (published in 1687) in which he said: "By blood I do not understand the aggregate of the four common humors - both biles, blood and pituita, but all that which flows continuously through the veins and arteries, and which consists of an infinite number of particles." In a 1666 publication, Malpighi described a human blood clot. He noted the redish cells which escaped when one washed the clot. He noted "some very small red particles" which were independent because they "can roll and turn helter-skelter in the little places." Thus Malpighi described (in letter format) red blood cells some 13 years before Leeuwenhoek (1661 vs 1674). Indeed, Malpighi also published observations on human red blood cells some eight years before Leeuwenhoek's 1674 publication on observations of "round globuls" in his own blood.

3) Jan Swammerdam (1637-1680)

First known illustration of human RBCs - Swammerdam

Swammerdam was trained as a physician and he visited Leeuwenhoek on several occasions in 1674. Leeuwenhoek wrote of these visits: "Dr. Swammerdam hath again within this fort-night visited me twice, accompanied with a Gentleman, to both of which I have shew'd many of these Microscopical Observations, and of such others as I had formerly spoken to him about; perceiving that his speculations are busy upon this subject, and that probably he will discourse more largely of it than I have done hitherto." Swammerdam used a glass capillary tube (invented by Leeuwenhoek in 1774) to withdraw human blood from a louse and to observe red blood cells. In a January 1678 letter to Thevenot, he refers to these "small globuls" and states "nothing more beautiful is to be seen than that, especially if one lets it run to and fro, as when every globulus separately is revolving like a circle." In this letter he includes the drawing shown in Fig 3, which is the first known illustration of human red blood cells. In a letter in April of the same year (1678), Swammerdam acknowledges learning the use of glass capillary tubes from Leeuwenhoek whom he describes in these terms: "It is impossible to go into discussion with him, as he is biased, and reasons in a very barbarical way, having no academic education." However, the interesting thing, in terms of priority of discovery of red blood cells, is evidence that Swammerdam may have made observations on the red blood cells of the frog in 1663 (or even earlier). Swammerdam is known to have demonstrated frog dissections in 1663 and in an undated manuscript appended to a 1737-38 book Swammerdam describes "a vast number of orbicular particles, of a flat oval but regular figure" in frog blood.

Additional reference:

The Microscope in the Dutch Republic by Edward G. Ruestow. Cambridge University Press, 1996.