Denis R. Alexander has spent the past forty years in the biological research community, most recently as the head of the Laboratory of Signalling and Development at The Babraham Institute in the U.K., where he also served as chair of the molecular immunology program. Dr. Alexander’s interest in human genetics was sharpened during a period (1981–1986) spent as associate professor on the American University of Beirut Medical Faculty. While there he helped to establish the National Unit of Human Genetics, which performed specialized diagnostic work and carried out research on the genetic diseases found in Lebanon. In 2006 Dr. Alexander established The Faraday Institute at St. Edmund’s College, Cambridge, where he is a fellow. Since that time, he has served as director of the Institute.

The Birth of Genetics

The birth of scientific ideas is never straightforward. Theories twist and turn. Blind alleys are pursued. The different results that seem so obviously connected with the benefit of hindsight are at first kept in splendid isolation, or even in opposition.

The birth of genetics—the word itself derived from the Greek "to give birth"—illustrates all these complexities. This is no heroic tale of one triumphant discovery after another, but a story about a dark maze full of groping investigators whose insights gradually enabled us to understand the language of genetics, a research field that now continues to expand its range of discoveries at a breathless pace.

Our own curiosity about what we now call "heredity" and "genetics" is not as modern as it may at first seem. Four thousand years ago the Assyrians and Babylonians were manipulating genes when they pollinated date palms, not knowing a thing about genetics. An Assyrian bas-relief sculpture shows the artificial pollination of date palms at the time of King Ashurnasirpal II of Assyria, who reigned from 884 to 859 BCE. The foundation we stand on today is built on a rich history, which began with questions about inheritance of traits in humans, animals, and plants. In time, the search was on for the pattern of this inheritance, and finally—in the twentieth century—the mechanism that eventually provided the basis for genetics. The birth of genetics is a story that takes us from ancient Greek speculation about twins, through the key discoveries of Gregor Mendel in the nineteenth century, and on to the 1953 discovery by James Watson and Francis Crick of the structure of DNA, the double-helix, which has become the biological icon of our age.

Early Ideas about Heredity

The early Greek philosophers speculated extensively about the mysteries of human heredity. Hippocrates (c. 460–370 BCE), considered the father of modern medicine, expounded an idea that much later came to be known as pangenesis, in which the material of inheritance is collected from throughout the body, delivered to the reproductive organs, and passed to the embryo at the moment of conception. As Hippocrates wrote, "The offspring resembles its parent because the particles of the semen come from every part of the body."

Aristotle (384–322 BCE) opposed this idea of inheritance by reassembled particles, objecting, not unreasonably, "How could there be such particles for abstract characters as voice or temperament, or from such nongenerating sources as nails or hair?" Instead Aristotle saw inheritance in more qualitative terms in which sperm provided the "active element," bringing the offspring to life, whereas the female contributed the nutrition that would help the offspring to grow. Aristotle considered two types of explanation for development. In the preformationist idea, a miniature individual exists in the egg or sperm, and then begins to grow into the offspring upon stimulation. In the theory of epigenesis, which Aristotle himself favored, the new organism develops from an undifferentiated mass by the addition of parts. As happens so often in the history of ideas, the Greek philosophers thus set the general agenda for the discussion about inheritance for the next two thousand years. Was it a question of physical particulate inheritance; or the passing on of preformed miniature individuals, like preformed Russian dolls, one inside the other; or the development of new organisms out of an undifferentiated mass? All these suggestions played important roles in the discussions that followed over the centuries.

Accurate observations of familial inheritance were more common than satisfying explanations of how the pattern of inheritance worked. Rules to prevent the consequences of what we now call hemophilia, in which blood fails to clot properly, can be found in the Jewish Talmud, and in 200 CE Rabbi Judah the Patriarch exempted a third son from circumcision if two elder brothers had bled to death. Even more striking is the Talmudic exemption that was also provided to the boy's male cousins, providing that they were sons of his mother's sisters, but not sons of his mother's brothers or his father's siblings. This exemption recognizes what we now call an X-linked pattern of inheritance, which is explained below.

Identical twins also drew much early attention and speculation. St. Augustine (354–430) argued against astrology on the grounds that twins born at virtually the same time, under the same planets, could have very different personalities. Much later Martin Luther (1483–1546) echoed the same argument, ridiculing astrology by pointing out that Esau and Jacob in the Old Testament were twins, yet had very different characters.

As the experimental method gained broader application with the scientific revolution of the sixteenth and seventeenth centuries, so some key findings were made that helped to lay the groundwork for the later science of genetics. James I's personal physician, William Harvey (1578–1657), who described the heart as a pump and explained its role in the circulation of the blood, also published On the Generation of Animals in 1651, arguing that all living organisms arose from eggs. Such was the fascination with the very small, aroused by new discoveries with the microscope, that preformationist ideas gained more attention, with either eggs or sperm being touted as the location of the "homunculus," the preformed miniature individual destined to become the new offspring. But as critics pointed out, the theory did not explain why offspring were such a mingling of the features of both parents.

The Swedish botanist Carl Linnaeus (1707–1778) first published his famous system of classification of all known living things in 1735, a classification that provides the basis for all further classifications right up to the present day. At the time Linnaeus believed that the number of species had been fixed at the time of the creation. But as Vítezslav Orel comments, "Subsequent experimental crossing of plants convinced him that hybridization gave rise to combinations of parental traits. He thought the genus rather than the species to be the basic unit of creation, and now admitted the possibility of new species appearing in nature and disappearing from it. He formed an open system, interpreting it in harmony with the Creator's design."

The introduction of the microscope opened up a fascinating new world of detailed biological structure that readily lent itself to mechanical types of description. Using the microscope, the polymath Robert Hooke (1635–1703) described for the first time in his famous work Micrographia (1665) the existence in...