by Isaac Asimov
Just as the revolution initiated by Copernicus was brought to fruition by Galileo, so the one initiated by Vesalius came to a head in the crucial discoveries of William Harvey. Harvey was an English physician and experimentalist, of the same generation as Galileo and William Gilbert, the experimenter with magnetism. Harvey’s particular interest was that vital body juice—the blood. What does it do in the body, anyway?
It was known that there were two sets of blood vessels: the veins and the arteries. (Praxagoras of Cas, a Greek physician of the third century B.C., had provided the name artery from Greek words meaning “I carry air,” because these vessels were found to be empty in dead bodies. Galen had later shown that in life they carry blood.) It was also known that the heartbeat drives the blood in some sort of motion, for when an artery was cut, the blood gushed out in pulses that synchronized with the heartbeat.
Galen had proposed that the blood seesawed to and fro in the blood vessels, traveling first in one direction through the body and then in the other. This theory required him to explain why the back-and-forth movement of the blood was not blocked by the wall between the two halves of the heart; Galen answered simply that the wall was riddled with invisibly small holes that let the blood through.
Harvey took a closer look at the heart. He found that each half was divided into two chambers, separated by a one-way valve that allows blood to flow from the upper chamber (auricle) to the lower (ventricle), but not vice versa. In other words, blood entering one of the auricles could be pumped into its corresponding ventricle and from there into blood vessels issuing from it, but there could be no flow in the opposite direction.
Harvey then performed some simple but beautifully clear-cut experiments to determine the direction of flow in the blood vessels. He would tie off an artery or a vein in a living animal to see on which side of this blockage the pressure within the blood vessel would build up. He found that when he stopped the flow in an artery, the vessel always bulged on the side between the heart and the block. Hence, the blood in arteries must flow in the direction away from the heart. When he tied a vein, the bulge was always on the other side of the block; therefore, the blood flow in veins must be toward the heart. Further evidence in favor of this one-way flow in veins rests in the fact that the larger veins contain valves that prevent blood from moving away from the heart. This mechanism had been discovered by Harvey’s teacher, the Italian anatomist Hieronymus Fabrizzi (better known by his Latinized name, Fabricius). Fabricius, however, under the load of Galenic tradition, refused to draw the inevitable conclusion and left the glory to his English student.
Harvey went on to apply quantitative measurements to the blood How(the first time’ anyone had applied mathematics to a biological problem). His measurements showed that the heart pumps out blood at such a rate that in twenty minutes its output equals the total amount of blood contained in the body. It did not seem reasonable to suppose that the body could manufacture new blood, or consume the old, at any such rate. The logical conclusion, therefore, was that the blood must be recycled through the body. Since it flows away from the heart in the arteries and toward the heart in the veins, Harvey decided that the blood is pumped by the heart into the arteries, then passes from them into the veins, then flows back to the heart, then is pumped into the arteries again, and so on. In other words, it circulates continuously in one direction through the heart-and-blood-vessel system.
Earlier anatomists, including Leonardo da Vinci, had hinted at such an idea, but Harvey was the first to state and investigate the theory in detail. He set forth his reasoning and experiments in a small, badly printed book entitled De Motus Cordis (Concerning the Motion of the Heart), which was published in 1628 and has stood ever since as one of the great classics of science.
The main question left unanswered by Harvey’s work was: How does the blood pass from the arteries into the veins? Harvey said there must be connecting vessels of some sort, though they were too small to be seen. This was reminiscent of Galen’s theory about small holes in the heart wall, but whereas Galen’s holes in the heart were never found and do not exist, Harvey’s connecting vessels were confirmed as soon as a microscope became available. In 1661, just four years after Harvey’s death, an Italian physician named Marcello Malpighi examined the lung tissues of a frog with a primitive microscope, and, sure enough, there were tiny blood vessels connecting the arteries with the veins” Malpighi named them capillaries, from a Latin word meaning “hairlike.” (For the circulatory system, see figure 13.1.)
Figure 13.1. The circulatory system.
The use of the microscope made it possible to see other minute structures as well. The Dutch naturalist [an Swammerdam discovered the red blood corpuscles, while the Dutch anatomist Regnier de Graaf discovered tiny ovarian follicles in animal ovaries. Small creatures, such as insects, could be studied minutely.
Work in such fine detail encouraged the careful comparison of structures in one species with structures in others. The English botanist Nehemiah Grew was the first comparative anatomist of note. In 1675, he published his studies comparing the trunk structure of various trees, and in 1681 studies comparing the stomachs of various animals.
CELL THEORY
The coming of the microscope introduced biologists, in fact, to a more basic level of organization of living things—a level at which all ordinary structures could be reduced to a common denominator. In 1665, the English scientist Robert Hooke, using a compound microscope of his own design, discovered that cork, the bark of a tree, was built of extremely tiny compartments, like a superfine sponge. He called these holes cells, likening them to small rooms, such as the cells in a monastery. Other microscopists then found similar cells, but full of fluid, in living tissue.
Over the next century and a half, it gradually dawned on biologists that all living matter is made up of cells and that each cell is an independent unit of life. Some forms of life—certain microorganisms—consist of only a single cell; the larger organisms are composed of many cooperating cells. One of the earliest to propose this view was the French physiologist René Joachim Henri Dutrochet. His report, published in 1824, went unnoticed, however; and the cell theory gained prominence only after Matthias Jakob Schleiden and Theodor Schwarm of Germany independently formulated it in 1838 and 1839.
The colloidal fluid filling certain cells was named protoplasm (“first form”) by the Czech physiologist Jan Evangelista Purkinie in 1839, and the German botanist Hugo von Mohl extended the term to signify the contents of all cells. The German anatomist Max Johann Sigismund Schultze emphasized the importance of protoplasm as the “physical basis of life” and demonstrated the essential similarity of protoplasm in all cells, both plant and animal, and in both very simple and very complex creatures.
The cell theory is to biology about what the atomic theory is to chemistry and physics. Its importance in the dynamics of life was established when, around 1860, the German pathologist Rudolf Virchow asserted, in a succinct Latin phrase, that all cells arise from cells. He showed that the cells in diseased tissue had been produced by the division of originally normal cells.
By that time it had become clear that every living organism, even the largest, begins life as a single cell. One of the earliest microscopists, Johann Ham, an assistant of Leeuwenhoek, had discovered in seminal fluid tiny bodies that were later named spermatozoa (from Greek words meaning “animal seed”). Much later, in 1827, the German physiologist Karl Ernst von Baer had identified the ovum, or egg cell, of mammals (figure 13.2). Biologists came to realize that the union of an egg and a spermatozoon forms a fertilized ovum from which the animal eventually develops by repeated divisions and redivisions.
Figure 13.2. Human egg and sperm cells.
Larger organisms, then, do not have larger cells than smaller organisms do; they simply have more of them. The cells remain small, almost always microscopic. The typical plant or animal’s cell has a diameter of between 5 and 40 micrometers (a micrometer is equal to about 1/25,000 inch), and the huma
n eye can just barely make out something that is 100 micrometers across.
Despite the fact that a cell is so small, it is by no means a featureless droplet of protoplasm. A cell has an intricate substructure that was made out, little by little, only in the course of the nineteenth century. It was to this substructure that biologists had to turn for the answers to many questions concerning life.
For instance, since organisms grow through the multiplication of their constituent cells, how do cells divide? The answer lies in a small globule of comparatively dense material within the cell, making up about a tenth its volume. It was first reported by Robert Brown (the discoverer of Brownian motion) in 1831 and named the nucleus. (To distinguish it from the nucleus of the atom, I shall refer to it from now on as the cell nucleus.)
If a one-celled organism was divided into two parts, one of which contained the intact cell nucleus, the part containing the cell nucleus was able to grow and divide, but the other part could not. (Later it was also learned that the red blood cells of mammals, lacking nuclei, are short-lived and have no capacity for either growth or division. For that reason, they are not considered true cells and are usually called corpuscles.)
Unfortunately, further study of the cell nucleus and the mechanism of division was thwarted for a long time by the fact that the cell is more or less transparent, so that its substructures cannot be seen. Then the situation was improved by the discovery that certain dyes would stain parts of the cell and not others. A dye called hematoxylin (obtained from logwood) stained the cell nucleus black and brought it out prominently against the background of the cell. After Perkin and other chemists began to produce synthetic dyes, biologists found themselves with a variety of dyes from which to choose.
In 1879, the German biologist Walther Flemming found that with certain red dyes he could stain a particular material in the cell nucleus which was distributed through it as small granules. He called this material chromatin (from the Greek word for “color”). By examining this material, Flemming was able to follow some of the changes in the process of cell division. To be sure, the stain killed the cell, but in a slice of tissue he would catch various cells at different stages of cell division. They served as still pictures, which he put together in the proper order to form a kind of “moving picture” of the progress of cell division.
In 1882, Flemming published an important book in which he described the process in detail. At the start of cell division, the chromatin material gathers itself together in the form of threads. The thin membrane enclosing the cell nucleus seems to dissolve; and at the same time, a tiny object just outside it divides in two. Flemming called this object the aster, from a Greek word for “star,” because radiating threads give it a starlike appearance. After dividing, the two parts of the aster travel to opposite sides of the cell. Its trailing threads apparently entangle the threads of chromatin, which have meanwhile lined up in the center of the cell, and the aster pulls half the chromatin threads to one side of the cell, half to the other. As a result, the cell pinches in at the middle and splits into two cells. A cell nucleus develops in each, and the chromatin material enclosed by the nuclear membrane breaks up into granules again (see figure 13.3).
Figure 13.3. Division of a cell by mitosis.
Flemming called the process of cell division mitosis, from the Greek word for “thread,” because of the prominent part played in it by the chromatin threads. In 1888, the German anatomist Wilhelm von Waldeyer gave the chromatin thread the name chromosome (from the Greek for “colored body”), and that name has stuck. It should be mentioned, though, that chromosomes, despite their name, are colorless in their unstained natural state, in which of course they are quite difficult to make out against the very similar background. (Nevertheless, they had dimly been seen in flower cells as early as 1848 by the German amateur botanist Wilhelm Friedrich Benedict Hofmeister.)
Continued observation of stained cells showed that the cells of each species of plant or animal has a fixed and characteristic number of chromosomes. Before a cell divides in two during mitosis, the number of chromosomes is doubled, so that each of the two daughter cells after the division has the same number as the original mother cell.
The Belgian embryologist Eduard van Beneden discovered in 1885 that the chromosomes do not double in number when egg and sperm cells are being formed. Consequently each egg and each sperm cell has only half the number of chromosomes that ordinary cells of the organism possess. (The cell division that produces sperm and egg cells therefore is called meiosis, from a Greek word meaning “to make less.”) When an egg and a sperm cell combine, however, the combination (the fertilized ovum) has a complete set of chromosomes; half contributed by the mother through the egg cell and half by the father through the sperm cell. This complete set is passed on by ordinary mitosis to all the cells that make up the body of the organism developing from the fertilized egg.
Even though the use of dyes makes the chromosomes visible, they do not make it easy to see one individual chromosome among the rest. Generally, they look like a tangle of stubby spaghetti. Thus, it was long thought that each human cell contained twenty-four pairs of chromosomes. It was not until 1956 that a more painstaking count of these cells showed twenty-three pairs to be the correct count.
Fortunately, this problem no longer exists. A technique has been devised whereby treatment with a low-concentration salt solution, in the proper manner, swells the cells and disperses the chromosomes. They can then be photographed, and that photograph can be cut into sections, each containing a separate chromosome. If these chromosomes are matched into pairs and then arranged in the order of decreasing length, the result is a karyotype, a picture of the chromosome content of the cell, consecutively numbered.
The karyotype offers a subtle tool in medical diagnosis, for separation of the chromosomes is not always perfect. In the process of cell division, a chromosome may be damaged or even broken. Sometimes the separation may not be even, so that one of the daughter cells gets an extra chromosome, while the other is missing one. Such abnormalities are sure to damage the working of the cell, often to such an extent that the cell cannot function. (This imperfection is what keeps the process of mitosis so accurate—not that it really is as accurate as it seems, but the mistakes are buried.)
Such imperfections are particularly dire when they take place in the process of meiosis, for then egg cells or sperm cells are produced with imperfections in the chromosome complement. If an organism can develop at all from such an imperfect start (and usually it cannot), every cell in its body has the imperfection: the result is a serious congenital disease.
The most frequent disease of this type involves severe mental retardation.
It is called Down’s syndrome (because it was first described in 1866 by the English physician John Langdon Haydon Down), and it occurs once in every thousand births. It is more commonly known as mongolism, because one of the symptoms is a slant to the eyelids that is reminiscent of the epicanthic fold of the peoples of eastern Asia. Since the syndrome has no more to do with the Asians, however, than with other ethnic groups, this is a poor name.
It was not until 1959 that the cause of Down’s syndrome was discovered.
In that year, three French geneticists—Jerome Jean Lejeune, Marthe Gautier, and Raymond Turpin—counted the chromosomes in cells from three cases and found that each had forty-seven chromosomes instead of forty-six. It turned out that the error was the possession of three members of chromosome pair 21. Then, in 1967, the mirror-image example of the disease was located. A mentally retarded three-year-old girl was found to have a single chromosome-21. She was the first discovered case of a living human being with a missing chromosome.
Cases of this sort involving other chromosomes seem less common but are turning up. Patients with a particular type of leukemia show a tiny extra chromosome fragment in their cells. This is called the Philadelphia chromosome because it was first located in a patient hospitalized in that city. Broken chromosomes,
in general, turn up with greater than normal frequency in certain not very common diseases.
ASEXUAL REPRODUCTION
The formation of a new individual from a fertilized egg that contains half its chromosomes from each of two parents is sexual reproduction. It is the norm for human beings and for organisms generally that are at our level of complexity.
It is possible, however, for asexual reproduction to take place, with a new individual possessing a set of chromosomes derived from one parent only. A one-celled organism that divides in two, forming two independent cells, each with the same set of chromosomes as the original, offers an example of asexual reproduction.
Asexual reproduction is very common in the plant world, too. A twig of some plant can be placed in the ground, where it may take root and grow, producing a complete organism of the kind of which it was once only a twig.
Or the twig can be grafted to the branch of another tree (of a diflerent variety sometimes) where it can grow and flourish. Such a twig is called a clone from the Greek word for “twig”; and the term clone has come to be used for any one-parent organism of nonsexual origin.
Asexual reproduction can take place in multicellular animals as well. The more primitive the animal—that is, the less diversified and specialized its cells—the more likely it is that asexual reproduction can take place.
A sponge, or a freshwater hydra, or a flatworm, or a starfish, can, any of them, be torn into parts; and these parts, if kept in their usual environment, will each grow into a complete organism. The new organisms can be viewed as clones.
Even organisms as complex as insects can in some cases give birth to one-parent young and, in the case of aphids, for instance, do so as a matter of course. In such cases, an unfertilized egg cell, containing only a half-set of chromosomes, can do without a sperm cell. Instead, the egg cell’s half-set merely duplicates itself, producing a full set all from the female parent; and the egg then proceeds to divide and become an independent organism, again a kind of clone.
