We are approaching the end of our lecture series. One major event remains to be discussed: the complete description of the human genome, announced in 2003.
A discussion of the genome has to begin with the mechanisms and laws that govern biological inheritance. This takes us back to Lecture 25, which described the revolution in biology. In that lecture we saw how evolution of the living world was discovered as a result of the explosion of knowledge about plant and animal species from all continents. The discovery of the genes as the carrier of genetic information fell into the same period - the mid-19th century - but only bore fruit half a century later.
The completion of the human genome sequence is the culmination of a branch of science that combines biology, chemistry, physics and mathematics to describe the laws of nature for the living world. It has given us answers to many questions and tools for experimentation that raises serious ethical questions. This lecture begins with a look at the historical development of the science and then proceeds to a discussion of scientific ethics as well as ethical applications of the results of science.
In 1856, three years before the publication of Darwin's Origin of Species, the Augustine monk Gregor Mendel began a series of experiments in the garden of his monastery in Brünn (today's Brno in the Czech Republic) in which he crossed varieties of the garden pea Pisum sativum under carefully controlled conditions. Mendel was a good mathematician and a good observer. The breeding of plants and animals through the crossing of varieties had of course been practiced for millennia before him. It had always been very much an empirical exercise. Mendel was convinced that it follows laws and that these laws are the same that control the occurrence of random events, in other words the laws of statistics. To understand what controls the biological inheritance of parental traits one therefore had to look not at a few well-bred specimens but at a large number of individuals.
Mendel derived three discoveries from his experiments. The fact that some traits disappeared completely in the first generation of hybrids but reappeared in a small number of individuals in later generations led him to conclude that units of heredity are transferred from both parents and continue to exist (and can therefore be inherited by future generations) in the offspring even if the associated trait is suppressed. He called these units gametes; today they are known as genes, and the word gametes is used for the sex cells that contain the many genes of a species.
Mendel's second discovery was that some traits, which he called dominant, suppressed the action of others, which he called recessive. The purple-flower trait in the garden pea, for example, is dominant, while the white-flower trait is recessive, which explained why the first generation of hybrids in his experiments had only purple flowers.
Mendel assumed that the transmission of traits follows the rules of random events. This allowed him to apply the mathematical laws of statistics and predict the appearance of traits over successive generations. By performing his experiments with thousands of plants Mendel also discovered that each parent transmits exactly half the available number of genes (called alleles today) to their offspring, which thus again have the full complement of genes.
After nearly a decade of experimentation with thousands of plants Mendel had unravelled the laws of biological inheritance and formulated the three laws known today as Mendel's Laws:
When he presented his findings in 1865 to the Natural Science Society of Brünn - that had only be founded three years before - he said of the work of other biologists:
Mendel's discoveries were a breakthrough in genetics but remained unknown to the scientific world for half a century. Charles Darwin was at a loss when it came to the laws of biological inheritance; in his most famous work On the Origin of Species by Means of Natural Selection he wrote in 1859:
In 1863 Darwin published Variations of Animals and Plants under Domestication. Its discussion of heredity followed Hippocrates' "pangenesis" theory that described inheritance as a blending of continuous elements: Minute particles from every part of the body were assumed to enter the seminal fluid of both parents and by fusion give rise to a new individual with both parents' traits. Mendel was aware of Darwin's theory of pangenesis, but his experiments and mathematical analysis allowed him to prove it wrong.
Mendel had discovered the rules of heredity, but he did not know how the rules were implemented in practice. This required two additional steps, the discovery and understanding of cell division, and the discovery of chromosomes as carriers of hereditary information. While the ground for these discoveries was laid during the 19th century, nearly all essential research that led to our present understanding of the physics and chemistry of heredity occurred in the second half of the 20th century. This research was pursued in several laboratories that were well supported financially, and new results no longer came from eminent scientists like Mendel but from gifted researchers in several laboratories, and the history of research that led to the mapping of the human genome contains many names.
Some of the processes that occur during cell division can be observed through ordinary light microscopes. Since 1848 it had been known that just before a cell splits into two, the cell nucleus divides into rodlike bodies that separate and provide the starting point for the two new cells. When experiments showed that these bodies absorb certain dyes they were named chromosomes. Later research showed that the number of chromosomes in every cell is constant for every species.
The property of chromosomes to be passed on during cell division made them strong candidates as carriers of genes. But to function in the way Mendel discovered, genes must not only be passed on during cell division; there also has to be a mechanism that splits genes into pairs of alleles and later recombines alleles into genes. This was confirmed when it was shown that cell division occurs in two forms.
In normal cell division ("mitosis") the chromosome duplicates itself, and two identical copies are handed over to the new cells. A second process of cell division ("meiosis") is responsible for the formation of sex cells (gametes). During meiosis chromosomes split into pairs that contain the alleles of their genes. Gametes therefore carry only half the amount of hereditary information. The full size of a chromosome is restored when gametes unite during fertilization; the result is a new individual with a new individual-specific chromosome.
An important process during meiosis is the "crossing over" of hereditary information. Chromosomes carry paternal and maternal information. When they divide during meiosis some of the paternal hereditary material is exchanged with maternal material, so that the information transferred to gametes contains a new hereditary mix. This opens the possibility for a practically limitless number of variations between individuals of a species, particularly in species with a large number of chromosomes.
Once the behaviour of chromosomes during cell division was understood it was clear that they were the physical carriers of Mendel's genes. When this state of understanding was reached between 1902 and 1909 several researchers began to study inheritance processes in species with a rapid turnover of generations and a small number of chromosomes. The fruit fly Drosophila melanogaster became particularly popular.
The large number of statistical observations on such species showed that not all inherited traits followed the distributions expected from Mendel's laws. This led to the realization that some genes, now called linked genes, are not assorted independently but transmitted together. Subsequent research showed this to be a function of the location of the genes in the chromosomes: Genes are linearly arranged in chromosomes, which also influences the probability of genes being involved in cross-overs.
The realization that genes are arranged in a determined pattern in chromosomes naturally posed the challenge of producing a chromosome map that shows the position of the various genes and their distances from each other (a map of the "genome"). The only way to produce such a map was to obtain the frequency distribution of recurring traits through many generations, from which conclusions can then be drawn how the genes have to be arranged to produce such a distribution. By the end of the 20th century this was achieved for species such as the fruit fly, the house mouse and corn (maize) but appeared impossible for humans.
The knowledge that genes are contained in chromosomes does not in itself explain how the genes achieve the transfer of hereditary material. The answer, and with it the key to genome maps of species with many chromosomes, was found in the study of cell chemistry, an area of research known as molecular genetics. By the mid-19th century it was known that cells contain proteins or amino acids. In 1869 another substance was extracted from cell nuclei. It contained nitrogen and phosphorus and was initially called nuclein; its modern name is deoxyribonucleic acid or DNA.
DNA is made up of the four basic building blocks adenine (A), guanine (G), cytosine (C) and thymine (T). Proteins are made up of 20 different amino acids. For the next eighty years after the discovery of DNA most biologists were convinced that the structure of DNA is far too limited to carry the huge variety of information and that this could only be achieved through the proteins. The demonstration that DNA is the carrier of hereditary information did not occur until about 1950 when experiments with radioactively labelled protein and DNA proved that only the DNA could penetrate into a cell, while the protein remained outside.
Once biologists had accepted DNA as the carrier of hereditary information their attention turned to the molecular structure of DNA. The modern model of DNA as two spirally wound chains (the "double helix") was developed in 1953. It describes the DNA molecule as a pair of complementary and identical strands linked through chemical bonds between T and A and between G and C. During replication before cell division the two strands separate, and each strand serves as a template for a new strand that forms.
Mapping the human genome became possible with the development of somatic cell genetics. Biochemists had known for some time how to grow certain organisms such as bacteria in cultures and investigate how their cells multiplied. In the late 1950s this technique was extended to cells of higher organisms. White cells taken from blood, marrow cells taken from bone, fibroplasts taken from skin could now be placed in cultures and multiplied.
The consequences were twofold. Cells multiply by dividing and handing on their complete DNA. Growing cells in cultures meant that identical copies of cells with identical DNA known as clones could be produced. It also meant that scientists had a large number of identical cells at their disposal for genetical study. Somatic cell genetics also learnt to fuse cells from different species (for example from humans and Chinese hamsters) and study how the properties of the resulting hybrid cell affect future "generations" of the cell culture. This opened the way to identify the genetic role of each gene in the human chromosome, in other words to produce a map of the human genome, by speeding up the collection of statistical data, eliminating the need to collect information over thousands of generations.
The mapping of the human genome was an international effort. Its completion in 2003 marked a major milestone in the development of science. Knowledge of the genome map lays the foundation for the understanding of many hereditary diseases and may lead to their avoidance or treatment.
The application of the new cell culture techniques has opened other possibilities often collectively referred to under the term genetic engineering. The most common application is the production of recombinant DNA in which one or more genes from one species are introduced into the DNA of a host species with the aim to achieve a certain change of host behaviour (for example increased resistance against herbicides). This has created wide-ranging debates about the ethical aspects of such procedures, questions to which we shall return later in this lecture.
The genetic information of an individual is carried in the sequence of the building blocks A, T, C and G on each DNA strand. This "code" contains instructions for the production of the 20 proteins that determine the structure and function of the organism. In principle, arranging three building blocks in all possible combinations allows the specification of 64 different instructions, more than enough to control the production of 20 proteins. (Two building blocks would allow only 16 combinations.) There is thus some redundancy in the system, but as the code is read from the beginning to the end and does not contain separators between instructions it is important that its sequence remains intact, or errors will occur. Such errors are called mutations and form the basis for the evolution of the species.
Given the high rate of cell divisions that occur during an individual's life it may be surprising that the occurrence of mutations is not much larger than observed. Cells have mechanisms to repair copy errors in DNA sequences. Of those mutations that remain, many affect recessive genes, so their existence does not become apparent immediately and then only in a relatively small number of individuals. The average mutation rate in humans is estimated as four in every 100,000 sex cells.
Mutations are not only the result of random accidents during DNA replication, they can also be triggered by environmental effects. This was demonstrated experimentally in 1926 when fruit flies exposed to X-ray radiation reacted with a high rate of mutation. Since then other forms of radiation and many chemicals have been shown to act as mutation agents.
An individual that carries mutated DNA will only affect the evolutionary history of the species if the mutation is retained over many generations and eventually becomes prominent. An understanding of hereditary evolution thus requires the statistical study of populations.
The foundations for the scientific study of populations were laid independently by Godfrey Harold Hardy and Wilhelm Weinberg in 1908. Using the scientific method to ignore secondary complications and reduce a problem to its essentials, they formulated what is now known as the Hardy-Weinberg Law: In the absence of agents for change the frequency distribution of gene alleles in a population does not change with time.
In a sexually reproducing population the conditions of the Hardy-Weinberg Law are met if marriage partners are chosen at random, all individuals have the same advantages and disadvantages with respect to reproduction and survival regardless of their individual DNA, there is no immigration or emigration, the population is large enough to absorb chance fluctuations, and mutations do not occur. Evolution becomes possible if any of these conditions is not met.
Mutations can establish themselves as a new trait of a species through selective mating and reproductive selection. Selective mating is the result of individual preferences, reproductive selection results from differences in reproductive success. Both lead to changes in the gene pool of a population. This is the basis of Darwin's process of natural selection.
This discussion of genetics and heredity has been by necessity brief and compressed, but it is sufficient to expand on questions left open in earlier lectures. It has clarified Darwin's idea of natural selection and can give meaning to the misleading slogan of the "survival of the fittest" coined by Herbert Spencer if the idea is applied to populations rather than individuals.
Philosophers have often wondered how the "survival of the fittest" can operate in a society that values compassion and altruistic acts. Such behaviour does not appear to give an individual an advantage in the "struggle of life." Seen from the perspective of the population as a whole it can be beneficial: Being compassionate and altruistic can be attractive to other members of the population, and selective mating is then one mechanism that enhances such traits in the population's gene pool.
One recurring theme in a political contest between the various classes in a society is the issue whether human traits are inherited or acquired from the environment. The debate about the "nature-nurture problem" does not question Mendelian genetics; on the contrary, the proponents of the hereditary character of traits such as obesity or intelligence base their arguments on Mendel's laws.
Much of the nature-nurture debate does not have much to do with science but is only a vehicle for the justification of ideological positions. Why spend large funds on the public school system if most children can only be expected to have inherited average intelligence; wouldn't it be better to establish a few elite schools for the gifted few? If, however, intelligence is not inherited but can be acquired it would be in society's interest to make best use of all available talent by exposing every child to the same level of education.
A scientific approach has to quantify the question: How much of a trait is inherited, how much of it is due to environmental influences? With some organisms the question can be answered experimentally. In a first experiment individual organisms are raised in carefully controlled identical environments; any variations between individuals are then clearly the result of genotype differences. In a second experiment individuals from identical genotypes are grown in widely varying environments; observed variations between individuals then have to be due to environmental effects.
Such experiments are of course easier to perform with plants or animals than with humans. (Some plants can guarantee identical genotype of individuals if they are taken from cuttings of a single plant.) The results show that heritability of traits varies considerably for different traits. That the same is true for humans has been established through studies of identical twins that were raised under different environmental conditions. The results can be summarized as:
Much of the work that led to the discovery of DNA and population dynamics was done during the period when the Soviet Union was a leading world power. The USSR government placed much emphasis on scientific research, which it hoped to use for the development of its resources. It therefore requires an explanation why one searches in vain for names of Soviet scientists in the history of genome research.
One of the foremost concerns of the Soviet government was the development of the country's agriculture under the difficult conditions of the short Siberian summer. Finding and selecting suitable plants was the task of the Institute of Applied Botany and New Crops in Saint Petersburg. Its director Nikolai Vavilov, a principled supporter of science in the service of the country's socialist development, based the institute's work programme firmly on Mendelian genetics. Assuming that most agricultural crops had originated from ancient civilizations he organized plant collections from many parts of the world and established 400 research and collection outposts in the USSR itself. As a result the USSR was leading in the organization of expeditions for the purpose of species collection and conservation and had samples of 50,000 varieties of wild plants and 31,000 grain specimens in its institutions.
A second centre of plant research was the Ukrainian All-Union Institute of Selection and Genetics in Odessa. One of its employees was Trofim Lysenko, a biologist who promised much faster development of new grain varieties suited to Siberia's climate. He promoted Lamarck's idea that traits acquired by a plant in response to environmental conditions are inherited by future generations. That Lamarck's theories were shown to be erroneous was of course well known in biological science, and Lysenko's claim that rye will result if wheat is grown under the right conditions was refuted by most Russian scientists. (An equivalent idea would be that dogs living in the wild give birth to foxes.)
But Lysenko was a political opportunist who exploited the climate of terror and fear under Stalin to foster his career. He accused Vavilov of separation of theory from practice and contempt of practical work and in 1935 managed to have him removed from his position as president of the Lenin All-Union Academy of Agricultural Sciences.
In 1936 a special session of the Academy was held to reconcile scientific genetics with Lysenko's teachings. Vavilov rightly refused to accept Lamarckism, and reconciliation proved impossible. In 1938 Lysenko became president of the Academy, and his supporters began a campaign against genetics as being part of the "powers of darkness" and in support of fascism. Two years later Vavilov was arrested and brought to trial in 1941. Sentenced to death, he died in prison of malnutrition in 1943. (Sheehan,1993)
The rise of Lysenko to gain control of biological science in the USSR is the worst legacy of the Stalin regime in the area of science. For nearly three decades it prevented Soviet geneticists from developing new grain varieties suitable for Siberian conditions and did immeasurable damage to the welfare of a whole generation.
Today Vavilov's work is an important cornerstone of the International Plant Genetic Resources Institute (IPGRI), a world institution to advance the conservation and use of plant genetic resources for the benefit of present and future generations. The IPGRI is located in Rome, Italy, and cooperates closely with the Food and Agricultural Organization (FAO) of the United Nations. Russia again honours Nikolai Vavilov as one of its greatest scientists and contributes to the work of the IPGRI.
In the system of human inquiry ethics is the inquiry into the nature of ultimate value and human standards, an undertaking also known as moral philosophy. A lecture series on the interaction of science, civilization and society is not the place for a full treatment of ethics. But the success of biochemistry in unravelling the physical basics of heredity produced new challenges for moral philosophy, and it is impossible to discuss the interaction between science, civilization and society without addressing its ethical dimensions.
It has to be realized that there are no definite and clear-cut answers to ethical questions about life and death. Issues such as abortion, euthanasia and suicide have been debated for millennia and were addressed in Lecture 9. Modern biochemistry and genetic engineering created the new discipline of bioethics that deals with questions such as what should be done with frozen human embryos kept for in vitro fertilization if the parents die before the embryos can be used (as happened in Australia in 1984) or whether it is acceptable to raise embryos in the wombs of surrogate mothers. Another new discipline is environmental ethics, which attempts to attach ethical value to the extinction of species, the clearing of rainforest or the production methods and use of genetically engineered species in modern husbandry and agriculture.
The fact that moral philosophy finds it difficult to provide answers to pressing questions of today should not be construed to indicate a superiority of science over philosophy. There are still many questions science cannot answer, and our understanding of time and space has not advanced much since the time of the early Indian philosophers. The difference is that we can live without immediate answers to unsolved scientific problems, but we have to adopt some code of ethics if we want to live together as social beings and cannot wait until moral philosophy provides all the answers.
The idea of deliberate genetic manipulation of humans developed from the obvious successes of breeders to improve inherited traits in plants and animals for the benefit of humans. Suggestions that the same principles can be applied to improve the human race itself can be found in documents of early civilizations, for example in the Old Testament and in Plato's description of the ideal society in his dialogue Republic. They took a more definite form through the work of Francis Galton, who introduced the term eugenics in 1883 for "the scientific improvement of the human genetic stock."
The aim of Galton's work was to improve the living conditions of the human species through scientific application of the principles of evolution. Coming from a wealthy family in colonial Britain he could not totally free himself from the prejudices of his class and was convinced that "the feeble nations of the world are necessarily giving way before the nobler varieties of mankind." But he spent much effort on experimental and analytical studies of heredity that might underpin eugenics and made significant contributions to mathematical statistics and the study of twins.
The negative and eventually catastrophic effects of eugenics developed through Galton's support of academic institutions. In 1904 Galton endowed the University of London with a research fellowship in eugenics. After his death a Chair of Eugenics at University College was created from funds provided in his will. Both were occupied by Karl Pearson, a brilliant mathematician and co-founder of biometrics who declared the higher birth rate of the poor a threat to civilization and promoted that they should be supplanted by "higher" races. The English Eugenics Society, founded by Galton in 1907 as the Eugenics Education Society, opposed Pearson but was itself ambivalent in its views on the "values" of different races.
Racist eugenics influenced the immigration policy of the USA. Immigrants from different nations did not find the same opportunities for personal advancement on arrival in their new homeland, and poor districts of cities and ghettos became populated with people from certain national backgrounds, while people from other nationalities were found preferentially in affluent suburbs. The Immigration Act of 1924 set quota for different nationalities based on their perceived tendency towards crime or other unwanted aspects of society. Racism against blacks found its expression in the founding of the American Eugenics Society by white supremacists in 1926.
Pseudo-scientific eugenics culminated in its use by the Nazi regime in Germany. The promotion of a programme to produce a "master race" through preferential mating of selected "superior" individuals was a minor aberration compared to the systematic murder of millions of people considered to be of an inferior race.
The discoveries of genetic science show that the idea of human races is ill-founded. Scientifically it has been replaced by the concept of populations with overlapping gene pools. Although the frequency distribution of genetic traits differs between populations, it is always possible to find individuals with a given trait in all populations. With regard to intellectual capacity this is borne out by the fact that university students today come from all human populations and show comparable achievement levels if given the same social support and conditions. The same is demonstrated by the speed with which achievements of different civilizations are adopted by others. (Lecture 6)
Genetic scientists sometimes distinguish between positive eugenics that aims at manipulating the human species towards a supposedly better gene pool and negative eugenics that aims at avoiding the birth of individuals with severe disorders. All civilizations practice negative eugenics by placing taboos on marriages between close relatives (between parents and their offspring, between siblings, in some civilizations also between more distant relatives). Modern science has opened the possibility of terminating a pregnancy if a prenatal test shows a major physical deformation, a procedure generally accepted by society today. Court decisions in Britain and the USA since the 1980s have established the acceptance of Down's syndrome as justification for the termination of a pregnancy. (Singer, 1995)
Whether society should ever accept the proposition that parents be allowed to influence the traits of their children and produce "designer children" is quite a different matter. The desirability of certain traits changes as cultures evolve and is therefore not accessible to scientific measurement. If the majority of parents select their children on the basis of skin colour, musical ability, sports performance, or other desirable features, the resulting changes may not necessarily be in the interest of future generations, who may find other qualities more important. If only a select few parents are allowed access to the procedure, the ethical question is - why not everyone else?
The success of genetic research has made the establishment of ethical principles for future uses of genetics an urgent task. Far from attempting to complete this task, I nevertheless want to conclude this lecture by pointing out some principles that appear worthy of consideration.
To begin with, any proposed ethical principle should be free of contradiction and hypocrisy. In Lecture 9 it was said that it is hypocritical to show concern for the unborn life without showing the same concern for human life once it has gone through birth and has to be supported with food, clothing and shelter. To close one's eyes before widespread misery in the world while campaigning against abortion is a clear case of double standard, comparable to the ethics of a slave society that has one standard of ethical behaviour towards the free and another standard towards the enslaved.
A common observation in everyday life is the fact that people apply different ethical standards towards humans and animals. If we consider it unethical to inflict deliberate harm on humans, why do we accept cruelty if it is directed towards animals? Even if we believe what the Bible tells us, that the Earth and everything on it was created to serve the needs of the human race, does that include the right to cruelty towards animals? There can be no doubt that many practices in modern factory farming inflict cruelty on animals. Hens held in cages in which they can barely move, cows under constant pain so that they produce more milk, pigs held in concrete pens barely larger than their own body - is this how humans should treat the creatures of Earth?
Extending the argument, what makes us believe that we can treat plants as if they were inanimate nature? It is well known that some plants react to being attacked by animals by warning other individuals of their species of imminent danger. Science has not yet established whether this involves some type of consciousness in the plants and whether plants have feelings. We find it hard today to comprehend how Descartes could declare that animals have no feelings. Maybe science will some day find how plants feel, and future generations will judge us the way we judge Descartes.
How should science be applied in an ethical way in the face of so many imponderables and unknowns? Scientists faced with environmental imponderables have begun to accept what is known as the "precautionary principle" as a guide for action: If the consequences of a proposed action are not yet understood society should abstain from that action. It may well be that the proposed action can turn out to be beneficial for Earth. But this fact has to be established first, and all possibility of catastrophic adverse results has to be excluded, before a decision is taken to proceed.
The precautionary principle is based on the fact, already pointed out in other contexts, that scientific progress can wait. Society can decide not to go ahead with a new scientific idea or a new technological development, but it cannot wait for the ultimate insight into the laws of social systems and the ultimate answers to all questions of ethics to run its daily affairs. If scientific discoveries are used before their consequences are fully understood - nuclear power stations, built before science knows what to do with spent nuclear fuel; genetically engineered plants and animals, created before the consequences are understood - such developments never occur out of scientific necessity; they are driven by other forces. The next and final lecture will discuss these in some detail.
Dobzhansky, T., A. Robinson, R. C. Richmond and F. H. Osborn (1995) The principles of genetics and heredity, Encyclopaedia Britannica 15th ed.
Dunn, L. C. (1995) Gregor (Johann) Mendel. Encyclopaedia Britannica 15th ed.
Abbey of St Thomas, Brno, Czech Republic Mendel Museum of Genetics, http://www.mendel-museum.org/eng/1online/ (accessed 23 April 2004).
Sheehan, H. (1993) Marxism and the Philosophy of Science: A Critical History 2nd ed. Humanities Press International, New Jersey. Also at
http://www.comms.dcu.ie/sheehanh/lysenko.htm (accessed 16 June 2004)
Singer, P. (1995) Ethics. Encyclopaedia Britannica 15th ed.
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