The Beginnings of Biochemistry. The Microscope

Of course, the body may be viewed as a machine, with-out necessarily considering it merely a system of levers and gears. There are methods of performing tasks other than by the purely physical interlocking of components. There is chemical action, for instance. A hole might be punched in a piece of metal by means of a hammer and spike, but it might also be formed by the action of acid.

The first chemical experiments on living organisms were conducted by a Flemish alchemist, Jan Baptista van Helmont (1577-1644), who was Harvey's contemporary. Van Helmont grew a willow tree in a weighed quantity of soil and showed that after five years, during which time he added only water, the tree had gained 164 pounds, while the soil had lost only two ounces. From this, he deduced that the tree did not derive its substance primarily from the soil (which was right) and that it derived it instead from the water (which was wrong, at least in part). Van Helmont did not, unfortunately, take the air into account and this was ironical, for he was the first to study airlike substances. He invented the word "gas" and discovered a vapor which he called ''spiritus sylvestris'' ("spirit of the wood") which, as it later turned out, was the gas we call carbon dioxide which is, in fact, the major source of a plant's subsistence.

Van Helmont's first studies of the chemistry of living organisms (biochemistry, we now call it) began to develop and grow in the hands of others. An early enthusiast was Franz de la Boe (1614-72), usually known by his Latinized name, Franciscus Sylvius. He carried the concept to an extreme of considering the body a chemical device altogether. He felt that digestion was a chemical process, for instance, and that its workings were rather similar to the chemical changes that went on in fermentation. In this he turned out to be correct.

He also supposed that the health of the body depended upon the proper balance of its chemical components. In this, too, there are elements of truth, though the state of knowledge in Sylvius' time was far too primitive to make more than a beginning in this direction. All Sylvius could suggest was that disease was an expression of a superfluity or a deficiency of acid.

The Microscope. The great weakness in Harvey's theory of circulation was that he could not show that the arteries and veins ever actually met. He could only suppose that the connections existed but were too small to see. At the time of his death, the matter was still unsettled and might have remained so forever if mankind had been forced to rely on its unaided eyes. Fortunately it did not have to.

Even the ancients had known that curved mirrors and hollow glass spheres filled with water seemed to have a magnifying effect. In the opening decades of the seventeenth century men began to experiment with lenses in order to increase this magnification as far as possible. In this, they were inspired by the great success of that other lensed instrument, the telescope, first put to astronomical use by Galileo in 1609.

Gradually, enlarging instruments, or microscopes (from Greek words meaning "to view the small") came into use. For the first time, the science of biology was broadened and extended by a device that carried the human sense of vision beyond the limit that would otherwise be imposed upon it. It enabled naturalists to describe small creatures with a detail that would have been impossible without it, and it enabled anatomists to find structures that could not otherwise have been seen.

The Dutch naturalist, Jan Swammerdam (1637-80), spent his time observing insects under the microscope and producing beautiful drawings of the tiny details of their anatomy. He also discovered that blood was not a uniform red liquid, as it appeared to the eye, but that it contained numerous tiny bodies that lent it its color. (We now know those bodies as red blood corpuscles.) The English botanist, Nehemiah Grew (1641-1712), studied plants under the microscope and, in particular, their reproductive organs. He described the individual pollen grains they produced. A Dutch anatomist, Regnier de Graaf (1641-73), performed analogous work on animals. He studied the fine structure of the testicles and the ovaries. In particular, he described certain little structures of the ovary that are still called "Graafian follicles."

More dramatic than any of these discoveries was that of the Italian physiologist, Marcello Malpighi (1628-94). He, too, studied plants and insects, but among his early work was the study of the lungs of frogs. Here he found a complex network of blood vessels, too small to see individually, which were everywhere connected. More-over, when he traced these small vessels back to their coalescence into larger vessels, the latter proved to be veins in one direction, arteries in the other.

Arteries and veins were, therefore, indeed connected by a network of vessels too small to be seen with the unaided eye, as Harvey had supposed. These microscopic vessels were named "capillaries" (from Latin words meaning "hairlike," though actually they are much finer than hairs). This discovery, first reported in 1660, three years after Harvey's death, completed the theory of the circulation of the blood.

Yet it was not Malpighi, either, who really put microscopy on the map, but a Dutch merchant, Anton van Leeuwenhoek (1632-1723), to whom microscopy was merely a hobby, but an all-absorbing one.

The early microscopists, including Malpighi, had used systems of lenses which, they rightly decided, could produce greater magnifications than a single lens alone could. However, the lenses they used were imperfect, possessing surface irregularities and inner flaws. If too much magnification was attempted, details grew fuzzy.

Van Leeuwenhoek, on the other hand, used single lenses, tiny enough to be built out of small pieces of flawless glass. He ground these with meticulous care to the point where he could get clear magnification of up to 200-fold. The lenses were, in some cases, no larger than the head of a pin, but they served Van Leeuwenhoek's purposes perfectly.

He looked at everything through his lenses and was able to describe red blood corpuscles and capillaries with greater detail and accuracy than the original discoverers, Swammerdam and Malpighi, could. Van Leeuwenhoek actually saw blood moving through the capillaries in the tail of a tadpole so that, in effect, he saw Harvey's theory in action. One of his assistants was the first to see the spermatozoa, the tiny tadpolelike bodies in male semen.

Most startling of all, though, was his discovery, when looking at stagnant ditch water under his lens, of the existence of tiny creatures, invisible to the naked eye, that, nevertheless, seemed to have all the attributes of life. These "animalcules" (as he called them) are now known as "protozoa" from Greek words meaning "first animals." Thus it became apparent that not only did objects exist too small to be seen by the naked eye, but living objects of that sort existed. A broad new biological territory thus opened up before the astonished gaze of men, and microbiology (the study of living organisms too small to be seen by the naked eye) was born.

In 1683, Van Leeuwenhoek even caught a fugitive glimpse of creatures considerably smaller than the protozoa. His descriptions are vague, of necessity, but it seems quite certain that his eye was the first in history to see what later came to be known as "bacteria."

The only other discovery of the era to match Van Leeuwenhoek's work, at least in future significance, was that of the English scientist, Robert Hooke (1635-1703). He was fascinated by microscopes and did some of the best of the early work. In 1665, he published a book, Micrographia, in which are to be found some of the most beautiful drawings of microscopic observations ever made. The most important single observation was that of a thin slice of cork. This, Hooke noted, was made up of a fine pattern of tiny rectangular chambers. He called these "cells," a common term for small rooms, and in later years, this discovery was to have great consequences.

Microscopy languished through the eighteenth century, chiefly because the instrument had reached the limit of its effectiveness. It was not till 1773, nearly a hundred years after Van Leeuwenhoek's original observation, that a Danish microbiologist. Otto Friderich Miiller (1730-84), could see bacteria well enough to describe the shapes and forms of the various types.

One of the flaws of the early microscopes was that their lenses broke up white light into its constituent colors. Small objects were surrounded by rings of color ("chromatic aberration") that obscured fine detail. About 1820, however, "achromatic microscopes," which did not produce such rings of color, were devised. During the nineteenth century, therefore, the microscope was able to lead the way to new and startling areas of biologic advance.