... an analysis that puts the final link in the chain, for here we see correlations between cytological evidence and genetic results that are so strong and obvious that their validity cannot be denied. This paper has been called a landmark in experimental genetics. It is more than that—it is a cornerstone.
Describing the paper 'A Correlation of Cytological and Genetic Crossings-over in Zea mays' published by Barbara McClintock and her student Harriet Creighton in the Proceedings of the National Academy of Sciences (1931), demonstrating that the exchange of genetic information that occurs during the production of sex cells is accompanied by an exchange of chromosomal material.

A million million spermatozoa,
All of them alive:
Out of their cataclysm but one poor Noah
Dare hope to survive.
And among that billion minus one
Might have chanced to be Shakespeare, another Newton, a new Donne—
But the One was Me.

Among innumerable footsteps of divine providence to be found in the works of nature, there is a very remarkable one to be observed in the exact balance that is maintained, between the numbers of men and women; for by this means is provided, that the species never may fail, nor perish, since every male may have its female, and of proportionable age. This equality of males and females is not the effect of chance but divine providence, working for a good end.

As a scientist and geneticist I started to feel that science would probably soon reach the point where its interference into the life processes would be counterproductive if a properly designed governing policy was not implemented. A heavily overcrowded planet, ninety-five percent urbanized with nuclear energy as the main source of energy and with all aspects of life highly computerized, is not too pleasant a place for human life. The life of any individual soon will be predictable from birth to death. Medicine, able to cure almost everything, will make the load of accumulated defects too heavy in the next two or three centuries. The artificial prolongation of life, which looked like a very bright idea when I started research in aging about twenty-five years ago, has now lost its attractiveness for me. This is because I now know that the aging process is so multiform and complex that the real technology and chemistry of its prevention by artificial interference must be too complex and expensive. It would be the privilege of a few, not the method for the majority. I also was deeply concerned about the fact that most research is now either directly or indirectly related to military projects and objectives for power.

As long as museums and universities send out expeditions to bring to light new forms of living and extinct animals and new data illustrating the interrelations of organisms and their environments, as long as anatomists desire a broad comparative basis human for anatomy, as long as even a few students feel a strong curiosity to learn about the course of evolution and relationships of animals, the old problems of taxonomy, phylogeny and evolution will gradually reassert themselves even in competition with brilliant and highly fruitful laboratory studies in cytology, genetics and physiological chemistry.

Beadle believed that genetics were inseparable from chemistry—more precisely, biochemistry. They were, he said, 'two doors leading to the same room'.

Biologists have long attempted by chemical means to induce in higher organisms predictable and specific changes which thereafter could be transmitted in series as hereditary characters. Among microorganisms the most striking example of inheritable and specific alterations in cell structure and function that can be experimentally induced and are reproducible under well defined and adequately controlled conditions is the transformation of specific types of Pneumococcus.

Cell genetics led us to investigate cell mechanics. Cell mechanics now compels us to infer the structures underlying it. In seeking the mechanism of heredity and variation we are thus discovering the molecular basis of growth and reproduction. The theory of the cell revealed the unity of living processes; the study of the cell is beginning to reveal their physical foundations.

Evolutionary plasticity can be purchased only at the ruthlessly dear price of continuously sacrificing some individuals to death from unfavourable mutations. Bemoaning this imperfection of nature has, however, no place in a scientific treatment of this subject.

Fossil bones and footsteps and ruined homes are the solid facts of history, but the surest hints, the most enduring signs, lie in those miniscule genes. For a moment we protect them with our lives, then like relay runners with a baton, we pass them on to be carried by our descendents. There is a poetry in genetics which is more difficult to discern in broken bomes, and genes are the only unbroken living thread that weaves back and forth through all those boneyards.

Genetic engineering is to traditional crossbreeding what the nuclear bomb was to the sword.

Geneticists believe that anthropologists have decided what a race is. Ethnologists assume that their classifications embody principles which genetic science has proved correct. Politicians believe that their prejudices have the sanction of genetic laws and the findings of physical anthropology to sustain them.

Genetics has enticed a great many explorers during the past two decades. They have labored with fruit-flies and guinea-pigs, with sweet peas and corn, with thousands of animals and plants in fact, and they have made heredity no longer a mystery but an exact science to be ranked close behind physics and chemistry in definiteness of conception. One is inclined to believe, however, that the unique magnetic attraction of genetics lies in the vision of potential good which it holds for mankind rather than a circumscribed interest in the hereditary mechanisms of the lowly species used as laboratory material. If man had been found to be sharply demarcated from the rest of the occupants of the world, so that his heritage of physical form, of physiological function, and of mental attributes came about in a superior manner setting him apart as lord of creation, interest in the genetics of the humbler organisms—if one admits the truth—would have flagged severely. Biologists would have turned their attention largely to the ways of human heredity, in spite of the fact that the difficulties encountered would have rendered progress slow and uncertain. Since this was not the case, since the laws ruling the inheritance of the denizens of the garden and the inmates of the stable were found to be applicable to prince and potentate as well, one could shut himself up in his laboratory and labor to his heart's content, feeling certain that any truth which it fell to his lot to discover had a real human interest, after all.

Genetics is the first biological science which got in the position in which physics has been in for many years. One can justifiably speak about such a thing as theoretical mathematical genetics, and experimental genetics, just as in physics. There are some mathematical geniuses who work out what to an ordinary person seems a fantastic kind of theory. This fantastic kind of theory nevertheless leads to experimentally verifiable prediction, which an experimental physicist then has to test the validity of. Since the times of Wright, Haldane, and Fisher, evolutionary genetics has been in a similar position.

Genetics is to biology what atomic theory is to physics. Its principle is clear: that inheritance is based on particles and not on fluids. Instead of the essence of each parent mixing, with each child the blend of those who made him, information is passed on as a series of units. The bodies of successive generations transport them through time, so that a long-lost character may emerge in a distant descendant. The genes themselves may be older than the species that bear them.

I am quite sure that our views on evolution would be very different had biologists studied genetics and natural selection before and not after most of them were convinced that evolution had occurred.

I assume that each organism which the Creator educed was stamped with an indelible specific character, which made it what it was, and distinguished it from everything else, however near or like. I assume that such character has been, and is, indelible and immutable; that the characters which distinguish species now, were as definite at the first instant of their creation as now and are as distinct now as they were then. If any choose to maintain... that species were gradually bought to their present maturity from humbler forms... he is welcome to his hypothesis, but I have nothing to do with it.

I immediately loved working with flies. They fascinated me, and followed me around in my dreams.

I should like to compare this rearrangement which the proteins undergo in the animal or vegetable organism to the making up of a railroad train. In their passage through the body parts of the whole may be left behind, and here and there new parts added on. In order to understand fully the change we must remember that the proteins are composed of Bausteine united in very different ways. Some of them contain Bausteine of many kinds. The multiplicity of the proteins is determined by many causes, first through the differences in the nature of the constituent Bausteine; and secondly, through differences in the arrangement of them. The number of Bausteine which may take part in the formation of the proteins is about as large as the number of letters in the alphabet. When we consider that through the combination of letters an infinitely large number of thoughts may be expressed, we can understand how vast a number of the properties of the organism may be recorded in the small space which is occupied by the protein molecules. It enables us to understand how it is possible for the proteins of the sex-cells to contain, to a certain extent, a complete description of the species and even of the individual. We may also comprehend how great and important the task is to determine the structure of the proteins, and why the biochemist has devoted himself with so much industry to their analysis.

I'd lay down my life for two brothers or eight cousins.

If we assume that there is only one enzyme present to act as an oxidizing agent, we must assume for it as many different degrees of activity as are required to explain the occurrence of the various colors known to mendelize (three in mice, yellow, brown, and black). If we assume that a different enzyme or group of enzymes is responsible for the production of each pigment we must suppose that in mice at least three such enzymes or groups of enzymes exist. To determine which of these conditions occurs in mice is not a problem for the biologist, but for the chemist. The biologist must confine his attention to determining the number of distinct agencies at work in pigment formation irrespective of their chemical nature. These agencies, because of their physiological behavior, the biologist chooses to call 'factors,' and attempts to learn what he can about their functions in the evolution of color varieties.

In a sense, genetics grew up as an orphan. In the beginning botanists and zoologists were often indifferent and sometimes hostile toward it. 'Genetics deals only with superficial characters', it was often said. Biochemists likewise paid it little heed in its early days. They, especially medical biochemists, knew of Garrod's inborn errors of metabolism and no doubt appreciated them in the biochemical sense and as diseases; but the biological world was inadequately prepared to appreciate fully the significance of his investigations and his thinking. Geneticists, it should be said, tended to be preoccupied mainly with the mechanisms by which genetic material is transmitted from one generation to, the next.

In its essence, the theory of natural selection is primarily an attempt to give an account of the probable mechanism of the origin of the adaptations of the organisms to their environment, and only secondarily an attempt to explain evolution at large. Some modem biologists seem to believe that the word 'adaptation' has teleological connotations, and should therefore be expunged from the scientific lexicon. With this we must emphatically disagree. That adaptations exist is so evident as to be almost a truism, although this need not mean that ours is the best of all possible worlds. A biologist has no right to close his eyes to the fact that the precarious balance between a living being and its environment must be preserved by some mechanism or mechanisms if life is to endure.

In the course of individual development, inherited characters appear, in general, earlier than adaptive ones, and the earlier a certain character appears in ontogeny, the further back must lie in time when it was acquired by its ancestors.

The foundations of population genetics were laid chiefly by mathematical deduction from basic premises contained in the works of Mendel and Morgan and their followers. Haldane, Wright, and Fisher are the pioneers of population genetics whose main research equipment was paper and ink rather than microscopes, experimental fields, Drosophila bottles, or mouse cages. Theirs is theoretical biology at its best, and it has provided a guiding light for rigorous quantitative experimentation and observation.

The fundamental problem in the origin of species is not the origin of differences in appearance, since these arise at the level of the geographical race, but the origin of genetic segregation. The test of species-formation is whether, when two forms meet, they interbreed and merge, or whether they keep distinct.

The nucleus has to take care of the inheritance of the heritable characters, while the surrounding cytoplasm is concerned with accommodation or adaptation to the environment.

The outlook seems grim. Natural selection under civilized conditions may lead mankind to evolve towards a state of genetic overspecialization for living in gadget-ridden environments. It is certainly up to man to decide whether this direction of his evolution is or is not desirable. If it is not, man has, or soon will have, the knowledge requisite to redirect the evolution of his species pretty much as he sees fit. Perhaps we should not be too dogmatic about this choice of direction. We may be awfully soft compared to paleolithic men when it comes to struggling, unaided by gadgets, with climatic difficulties and wild beasts. Most of us feel most of the time that this is not a very great loss. If our remote descendants grow to be even more effete than we are, they may conceivably be compensated by acquiring genotypes conducive to kindlier dispositions and greater intellectual capacities than those prevalent in mankind today.

The prize is such an extraordinary honor. It might seem unfair, however, to reward a person for having so much pleasure over the years, asking the maize plant to solve specific problems and then watching its responses.

The problem [with genetic research] is, we're just starting down this path, feeling our way in the dark. We have a small lantern in the form of a gene, but the lantern doesn't penetrate more than a couple of hundred feet. We don't know whether we're going to encounter chasms, rock walls or mountain ranges along the way. We don't even know how long the path is.

The process of mutation is the only known source of the raw materials of genetic variability, and hence of evolution. It is subject to experimental study, and considerable progress has been accomplished in this study in recent years. An apparent paradox has been disclosed. Although the living matter becomes adapted to its environment through formation of superior genetic patterns from mutational components, the process of mutation itself is not adaptive. On the contrary, the mutants which arise are, with rare exceptions, deleterious to their carriers, at least in the environments which the species normally encounters. Some of them are deleterious apparently in all environments. Therefore, the mutation process alone, not corrected and guided by natural selection, would result in degeneration and extinction rather than in improved adaptedness.

The science of genetics is in a transition period, becoming an exact science just as the chemistry in the times of Lavoisier, who made the balance an indispensable implement in chemical research.

The theory of evolution by natural selection is an ecological theory—founded on ecological observation by perhaps the greatest of all ecologists. It has been adopted by and brought up by the science of genetics, and ecologists, being modest people, are apt to forget their distinguished parenthood.

The three of us have worked on the development of the small and totally harmless fruit fly, Drosophila. This animal has been extremely cooperative in our hands - and has revealed to us some of its innermost secrets and tricks for developing from a single celled egg to a complex living being of great beauty and harmony. ... None of us expected that our work would be so successful or that our findings would ever have relevance to medicine.

The worst thing that will probably happen—in fact is already well underway—is not energy depletion, economic collapse, conventional war, or the expansion of totalitarian governments. As terrible as these catastrophes would be for us, they can be repaired in a few generations. The one process now going on that will take millions of years to correct is loss of genetic and species diversity by the destruction of natural habitats. This is the folly our descendants are least likely to forgive us.

We are compelled to drive toward total knowledge, right down to the levels of the neuron and the gene. When we have progressed enough to explain ourselves in these mechanistic terms...the result might be hard to accept.

We are now witnessing, after the slow fermentation of fifty years, a concentration of technical power aimed at the essential determinants of heredity, development and disease. This concentration is made possible by the common function of nucleic acids as the molecular midwife of all reproductive particles. Indeed it is the nucleic acids which, in spite of their chemical obscurity, are giving to biology a unity which has so far been lacking, a chemical unity.

We are survival machines—robot vehicles blindly programmed to preserve the selfish molecules known as genes. This is a truth which still fills me with astonishment.

We may consequently state the fundamental theorem of Natural Selection in the form: The rate of increase in fitness of any organism at any time is equal to its genetic variance in fitness at that time.

We spend long hours discussing the curious situation that the two great bodies of biological knowledge, genetics and embryology, which were obviously intimately interrelated in development, had never been brought together in any revealing way. An obvious difficulty was that the most favorable organisms for genetics, Drosophila as a prime example, were not well suited for embryological study, and the classical objects of embryological study, sea urchins and frogs as examples, were not easily investigated genetically. What might we do about it? There were two obvious approaches: one to learn more about the genetics of an embryologically favourable organism, the other to better understand the development of Drosophila. We resolved to gamble up to a year of our lives on the latter approach, this in Ephrussi's laboratory in Paris which was admirably equipped for tissue culture, tissue or organ transplantation, and related techniques.

What politicians do not understand is that [Ian] Wilmut discovered not so much a technical trick as a new law of nature. We now know that an adult mammalian cell can fire up all the dormant genetic instructions that shut down as it divides and specializes and ages, and thus can become a source of new life. You can outlaw technique; you cannot repeal biology.
Writing after Wilmut's successful cloning of the sheep, Dolly, that research on the cloning of human beings cannot be suppressed.

When there are two independent causes of variability capable of producing in an otherwise uniform population distributions with standard deviations s₁ and s₂, it is found that the distribution, when both causes act together, has a standard deviation vs₁² + s₂². It is therefore desirable in analysing the causes of variability to deal with the square of the standard deviation as the measure of variability. We shall term this quantity the Variance of the normal population to which it refers, and we may now ascribe to the constituent causes fractions or percentages of the total variance which they together produce.

While our behavior is still significantly controlled by our genetic inheritance, we have, through our brains, a much richer opportunity to blaze new behavioral and cultural pathways on short timescales.