Show me your genes and I will tell you who you are
Dr. David Heaf
URL source of this article: www.ifgene.org/heaf3.htm. Originally published in New View, 4th Quarter, Autumn 2000, pp 7-12"Monday 26th June 2000 will be remembered as the day when humankind learned, in a sense, what it is to be human."1 You might be forgiven for thinking something momentous has happened. You may even remember for the rest of your life what you were doing when the news reached you. Certainly some important people thought something important had happened. Bill Clinton said, "This is the most wondrous map ever produced by mankind." Tony Blair called it, "a breakthrough that opens the way for massive advancement in the treatment of cancer and hereditary diseases, and that is only the beginning."
So what in fact had happened? The leaders of the publicly sponsored Human Genome Project (HGP) and Craig Venter who leads the parallel private initiative of the company Celera Genomics chose that day to announce that they had completed the first working draft of the complete set of human genetic information, the human genome (see Box 1 for other basic terms). This feat has been likened to the 1953 conquest of Everest, but when what the HGP has accomplished is examined, a more apt comparison would be setting up base camp for the final ascent. 85% of the genome has had its base sequence worked out roughly and 24% has been sequenced to 99.99% accuracy, a standard that needs the whole sequencing process to be repeated about 10 times (see Box 2 on sequencing). Furthermore, with some 3.1 billion base pairs in the genome even when the whole genome has been sequenced to that accuracy, there could remain some 310,000 errors, and these in only a 'generic' genome of the few who contributed their DNA to the sample. There remain too the genetic differences between human individuals. These are important if Tony Blair's prediction for disease treatment is to be realised. These differences, most of which are accounted for by 'single nucleotide polymorphisms' (SNPs),2 are also receiving intensive research and with the extraordinary acceleration of the project through mechanisation combined with computing power, sequencing the genomes of individuals may be only a few years off.3 The remaining 15% of the genome which has not yet been sequenced is likely to prove very resistant to sequencing by present methods for technical reasons arising from the repetitive nature of the sequences it contains.4 Even imagining that the 26th June was the announcement of the accurate sequence, nobody knows what 97% of it does and only 38,000 genes are as yet known, less than a third of what may yet be discovered. So to return to our Everest metaphor, no summit flag has yet been planted.
Why then all the song and dance now? One likely factor is the last-minute rapprochement in Spring 2000 between the private and public efforts which until then appear to have been competing against each other. "An unseemly feud would have marred their effort to present the 'mapping' of the human genome as a noble and high-minded endeavour."5 Another likely factor is that most biotechnology research ventures need to keep up the hopes of investors public and private in order to keep the cash coming in. The final decision to sequence the whole genome was taken in 1990. In 1991 in the USA alone $130 million was spent on it. In 1998 the expenditure was $250 million. And there are now teams in some 18 other countries involved in the effort. Britain's Sanger Centre at Cambridge, funded to the level of £210m by the Wellcome Trust, contributed about a third of the sequence data obtained so far.6 Even when the whole sequence is known, which could be many years away, will we have the 'essence of mankind'?7
1. Chromosomes, genes and DNA
Basics: Figure 1 shows an artist's impression
of an electron microscope picture of a typical representative of one of the 100 trillion
or so cells in the human body. Coming from one of the chromosomes of the 23 pairs in the
cell's nucleus is a purely diagrammatic representation of a chain of DNA (Deoxyribose
Nucleic Acid). Each of the two strands in the DNA double-helix chain is made of a backbone
of repeating sugar and phosphate molecules (shown as a helical ribbon in Fig. 1).
Chemically, DNA is thus a polymer. To each sugar molecule is attached one of four
molecules called bases, designated by the letters, C, A G and T, the first letters of
their chemical names cytosine, adenine, guanine, and thymine. The group comprising
phosphate, sugar and attached base is called a nucleotide. Bases on opposite complementary
strands pair up, T always with A, C always with G. The weak attraction or bonding between
the two bases of the pair help to hold the two strands of the helix together. It is this
pairing and bonding of the bases combined with their linear distribution along the DNA
strand which makes it possible to determine the sequence of bases in DNA. There are some
3.1 billion base pairs in human DNA. The chromosomes vary in size having 50-250 million
base pairs each.
Figure 1: Artists impression of a cross section of a cell with chromosomes and DNAThe gene: a fuzzy concept. A classical geneticist sees a gene as a unit of heredity transmitting definite characteristics (e.g. eye colour) from parent to offspring according to Mendel's laws of inheritance. To a molecular biologist it is a stretch of bases on a DNA strand that codes for a unit of function in the cell. An evolutionary biologist regards a gene as a cell component robust enough to serve as the basis for evolution. And the biochemist's gene is a piece of DNA that the cell needs in order to make a protein, which could be either an enzyme needed to facilitate a chemical reaction or a protein which is part of the structure of cells and tissues of the body. Proteins are built up of chains of some 20 different amino acids, each coded for by its own triplet of adjacent DNA bases from among the foursome C, A, G and T.
The gene concept gets even fuzzier when the following properties are considered: Genes can split into several parts along the DNA chain or have base sequences which overlap with other genes. They often have no defined ends because of their associated flanking and control sequences. The fluidity of the genome and so called 'jumping genes' means that genes often have no permanent location in chromosomes or DNA. The totality of the genes making up the human genome is not yet known, but is likely to be between 40,000 and 140,000. Furthermore, 97% of the DNA is thought not to code for proteins and is sometimes referred to as 'junk DNA'. It probably plays an important part in the dynamic and structural organisation of the DNA such as controlling the expression of genes.
There is a 98.5% match between human and chimpanzee DNA and a 99.9% match between the DNA of different human individuals. According to the molecular geneticists then, individual genetic differences, including maleness and femaleness are therefore largely attributable to the remaining 0.1% of the DNA.
Box 2. Mapping and Sequencing the Human Genome
Mapping: One of the earliest maps of the human genome came from studying how characteristics are passed on in families. If two (or more) characteristics tend to crop up together, we might suppose that they were coded for by genes on the same chromosome. However, even if two characteristics are coded for on the same chromosome, occasionally they will occur separately because of the occasional jumbling up of the chromosomes (meiotic crossing over) that happens when sperm cells and egg cells are formed. If two characteristics that are on the same chromosome get separated frequently, then we can conclude that they are far away from each other on the chromosome. If they hardly ever get separated, then the two characteristics must be very close together on the chromosome. By looking at how characteristics are inherited in patterns, we can draw up a vague map of where the genes are on the chromosomes. The disadvantage of this approach is that humans take a long time to grow up and have children, so it is only usually possible to look at three or four generations of a single family at a time. Also, there are often not enough children in each family to work out the gene positions accurately.
Whilst the chromosome maps from this classical genetics approach provide useful orienteering information, to obtain the actual base sequences of the DNA in the genes of the chromosome, molecular biological techniques are necessary.1 One such technique involves working backwards from the protein coded for by a gene. There is a correspondence between the genetic code of bases in DNA and the amino acids, the building blocks of protein. From the amino acid structure of a protein a short strand of DNA can be synthesised, called a probe, which when mixed with the chromosomes or DNA containing the gene coding for the protein will bind firmly to it. If the probe has a marker attached to it which can be seen by microscopy, the position the marker shows on the chromosome or DNA indicates the position of the gene.
Sequencing: Because of the high degree of similarity of DNA from different people, DNA for working out its sequence of bases was obtained from the sperm and blood of only a dozen or so anonymous volunteers and extracted into a watery solution with added chemicals to protect it.2 Using enzymes it was 'cut up' into lengths of about 150,000 bases to make a living 'library' of human DNA stored in artificial chromosomes in bacteria (BACs). By bacterial cloning techniques the BACs can be multiplied, kept pure, sampled when needed and the human DNA recovered. As the human DNA in the BACs is still too long for the sequencing step it is cut into smaller fragments of 400-700 bases and this is done so that the sequences of the fragments overlap with one another. To obtain sufficient material for the next step each of the fragments is copied many times using the polymerase chain reaction (PCR).
Any length of DNA can be copied, provided it has a start signal at one end and a stop signal at the other end. The DNA is added to a test tube full of DNA ingredients, such as the four bases (A, C, G and T), sugars and phosphate. DNA polymerase, the enzyme that catalyses the formation of DNA, is also present. The mixture is heated, so that the weak bonds between the bases in the two strands of the DNA (see Fig. 1) are broken. Once these strands are separated, the mixture is cooled and each strand can act as a template for DNA polymerase, so complementary sequences are soon generated for each of the original strands. Then the mixture is heated again, so that the bonds are broken and the strands separate. This time, there are four strands of DNA to act as templates once the mixture is cooled. The cycle of heating followed by cooling is repeated many times, and the amount of DNA is doubled with each cycle.
To sequence a length of DNA, a copy of the DNA to be sequenced is added to four test tubes. Within each of these test tubes are all the ingredients to make new DNA (see previous para.). There is, however, one important difference between the contents of these test tubes, and the usual ingredients for making DNA. The difference is that in each of the test tubes, one of the bases A, C, G or T has been replaced with a modified version of the base which when inserted prevents the DNA strand from growing further. In the test tube where A has been replaced with the modified version of A, there will be DNA fragments of different lengths, each one terminating in one of the modified bases. Wherever there is an A in the original sequence, some of the growing chains of DNA in the A test tube will have been stopped at that position.
To identify the fragments of DNA that have been produced, the DNA pieces are separated in a gel through which the movement of DNA fragments is partially impeded because it is made up of long, polymer molecules. An electrical field is applied across the gel, so that one end of the gel is negatively charged and the other end is positively charged. The pieces of DNA are added to the gel at the negatively charged end. Because DNA is slightly negatively charged, the bits of DNA begin to move through the gel, away from the negatively charged end and towards the positively charged end. The speed with which the DNA moves depends on its size the smaller pieces of DNA are able to move more quickly through the gel. After a while, the pieces of DNA are spread out across the gel. The smallest ones have nearly reached the positively charged end while the largest pieces have hardly moved from their starting position.
Modern sequencing machines have the gel in capillary tubes. The reactions in our four test tubes can be combined and added to one capillary. In which case the emerging DNA chains, terminating in modified A, C, G or T, are detected electronically from the light they emit when mixed with fluorescent dyes specific for the four different bases and illuminated by a laser. The results are fed into a computer. Some labs still use multi-lane gels run between two glass plates. Here detection can be by radioactive tagging followed by radiography of the gel. In this case the contents of the four tubes are kept separate and placed in the gel's electric field in four separate lanes.
Figure 2: Radiograph of an electrophoresis gel of fragments of DNA showing the four lanes corresponding to the bases A, C, G & T. Each dark horizontal band on the radiograph is produced by the radioactive tag in a short strand of DNA, the longest strands at the top and the shortest at the bottom. The direction of flow was from top to bottom. The sequence, 'read' from the bottom, is TGTACAACTTTTA etc.
The base sequence emerging from the capillary or 'read' from the gel (see Fig. 2 above) is the sequence of just one of the millions of DNA fragments created at the beginning. The fragment sequences are fed into powerful computers programmed to do a huge linear 'jig-saw puzzle' by working out what the sequence of the DNA chain was before it was cut into fragments. The following diagram illustrates with three fragments of DNA how use is made of the overlaps in the sequences of the fragments:
1. The Sanger Centre web site: www.sanger.ac.uk/HGP/draft2000/how.shtml
2. www.sanger.ac.uk/HGP/draft2000/who.shtml and www.ornl.gov/hgmis/faq/seqfacts.html#whose
It was recognised at the outset of the HGP that once it had reached its goal it would have ethical, legal and social implications (ELSI). The ELSI program ran in parallel from the beginning, drawing on some 3-5% of the overall funding of the project. Already by 1991 the key concerns were being discussed in workshops: eugenics, racism, genetic discrimination, genetic determinism, reductionism, control of genetic information, screening, counselling, impact on procreative liberty, patent rights, gene therapy and enhancement.8 As this ground has already been dug over so much in the press, both lay and technical, we shall not visit it again here. For an excellent insight into the key issues the reader is referred to Bryan Appleyard's Brave new Worlds: Genetics and the Human Experience.9 As we have seen, the HGP is far from completion and has thus not had time to do any damage. We can only speculate at this stage what some of the consequences might be, good or evil. But we can look at it for what it is in itself, intrinsically, in principle. We can examine the world views behind it and its proposed applications. In doing so we come to the difficulties science has with understanding what being human and becoming ill mean, which will be the main focus of the remainder of this article.
The biological sciences have laboured for more than two centuries under a methodological problem in their underlying thinking. They have tended to assume that the mechanistic thinking which works well in physics can be transferred with a few modifications to biology. And biology has now become the study of the behaviour of molecules. It has long since given up any aspiration to cognitive faculties appropriate for the understanding of life. We can distinguish three different cognitive approaches which belong to different realms of science. In the science of physics we can find all the circumstances which are necessary to bring about a given phenomenon and by thinking about the connections arrive at a law. We can seek out primal phenomena in which the law becomes visible. Such is the approach to inorganic nature. But in organic nature, the realm of biology, to reach a comparable level of certainty we need to be able to apprehend the type at work in the organism concerned and follow it through in all its ramifications in the forms and functions under study. This is not to say that organisms are not also subject to the laws of physics. When we come to the human being, we rise to a new level in the scientific process. Of course, as with any animal, there is much about human beings which is purely representative of the type, but the science of the human being needs to take into consideration an additional factor the individuality. Here individuality takes on the role that type does for animals. Here we have briefly outlined a Theory of Knowledge Implicit in Goethe's World Conception as set out by Rudolf Steiner in 1886.10 Indeed, 'Down to the smallest particle of his substance, man in his form and configuration is a product of the organisation of the Ego'.11 Here is meant the essential self, that principle of individuality in each person. So just as the animal type stamps itself on the base sequences of its DNA, so too the human individuality, working as the incarnate ego through forces which form the physical body, can to a greater or lesser degree stamp itself on the 'smallest particles of his substance', the composition of his DNA. Therefore, when we have sequenced the whole of the generic human being, we will still be a very long way from knowing the 'essence of mankind' or 'what makes us human', as James Watson the co-discoverer of the DNA double-helix described the molecule.12 That essence, the human is the individual. And in all our considerations of what should be done with the information pouring hour by hour into the databases of the HGP at the very least we should not overlook that fact.
In thinking 'what it is to be human' is coded by the DNA, even if this idea is meant 'in a sense', we divert attention away from the reality of what it is to be human. We fall into the ongoing error in biology of collecting data, applying statistics and reaching generalisations within degrees of probability, albeit the 99.99% probability of the HGP's 'gold standard', which even if we were studying an animal, would leave us blind to the type manifesting in our sample. We become dependent on the inductive method. We collect observations of a sufficient number of instances and arrive at a generalisation about them which is always only provisional because a new instance may turn up which forces us to modify our generalisation. But once the type has been grasped, the result is never provisional. This is best illustrated by Goethe's correct prediction and discovery of the human premaxilla (intermaxillary bone) despite the scientific opinion of his time which held that the absence of the bone distinguished man from animal. He correctly realised from the inner lawfulness of the type that the human form too must manifest the bone.
The HGP takes the study of anatomy to its ultimate extreme. As with most anatomical research, what was once living has to be killed and fixed what once in-formed it is driven out. This shows vividly in Rembrandt's painting The Anatomy Lesson of Dr. Tulp (Figure 2. below) in which the various gazes into the middle distance seem to convey an atmosphere of wonderment for the whereabouts of the departed soul. In extracting and preserving the DNA, the sequence of the human genome at best represents a snapshot in the temporal stream that characterises every living process. It gives us human molecular anatomy of the 21st century and thus cannot be seen as finished for all time. After all, even the summit of Everest is not a fixed point, neither in space nor above sea level.
Figure 2: The Anatomy Lesson of Dr. Tulp by Rembrandt
Understanding that the human individuality stamps itself on its manifest form right down to the level of the DNA admittedly involves a radical departure from current western thinking about the human being. It involves looking at a broader time span than a single life. We are used to thinking of heredity as involving something being passed on to us by our parents. It is something done to us, so to speak. But Rudolf Steiner describes from spiritual scientific observation how the incarnating individual works down through the stream of heredity many generations in advance of the one in which he will manifest on earth, preparing the qualities he is ultimately to inherit. In a sense, he inculcates these qualities into his ancestors albeit in concert with other beings, including future siblings, who are active in his hereditary stream until a physical body can be born to which he feels drawn.13 Dominic Lawson, former editor of The Spectator had a sense for the deep connection of individuality and bodily form when he wrote:
"Two emotions coursed through me as the consultant gave me a guided tour of the stigmata of Down's Syndrome. The first was anger. While I understood that the doctor was only doing his professional duty to explain as clearly and as quickly as possible the condition of his patient I wanted to shout out, " This is my daughter you are prodding, not some random strip of flesh." The second emotion was love...I felt an intense, almost physically painful love for this third daughter....the Down's baby is as much the product of his or her parent's genes as any other child... There is no possible alternative Domenica Lawson without Down's Syndrome. That is her identity, her very essence, along with all the other genes she has inherited from us."14 And yet no matter how individual it is, the DNA cannot be the origin of the individuality. This runs counter to the view amongst certain biologists that higher order attributes of an organism are an 'emergent' property of the lower order attributes. Put simply, properties of molecules are supposed to emerge from the association of its individual atoms, properties of organs from collections of molecules, consciousness from interaction of organs and so on. It is reductionism in new clothes. In contrast to this, ideas of causation originating from Aristotle and, later in the Middle-Ages, Thomas Aquinas, are used in Catholic ideology to argue that the human soul is present in the embryo right from the moment of conception.15 Their point being that cells in the embryo cannot 'cause' the higher level of order of the soul. The soul provides the ordering influence from the start, right down to the level of the cells. Personhood starts at conception.16 Rudolf Steiner too describes how the ordering element, the form of the human body what he calls the 'spirit germ' enters at conception. This cosmic origin of form thus transcends heredity. But in contrast to Catholic ideology, Steiner points out that the spirit soul elements delay their entry into the embryo until the 17th - 20th day.17 Incidentally it is worth noting here that in the UK, experimentation on the human embryo is permitted only up to the 14th day of development when a visible change takes place in the embryo. The primitive streak forms, evidencing the rudiments of the nervous system and marking the beginning of a new phase of development.
The DNA-thinker has been seduced by the admittedly huge informational complexity of the DNA, albeit with its simple code based on A, C, G or T. Molecular biological dogma long held that information flow was from DNA to protein to organic form. The DNA was supposedly the blueprint. More and more phenomena are being discovered that erode this simplistic picture. Not only does control information flow in the reverse direction that is from cell periphery to the DNA , but also processes totally outside the DNA, so called epigenetic processes play an important part in the stream of heredity.18 With the help of enzymes, the organism manages its DNA to suit its purposes. The DNA comes into existence, is repaired, copied and maintained by the organism. Like all substances in the organism, it is in a state of constant flux and turnover, something which the fixed models such as in Fig. 1 conceal from our imagination. And no single molecule, despite its size or complexity, deserves to be given pride of place in this organismic view. The organism is primal. But such a thought sorely challenges the DNA-thinker. Where then is the organism? What material object represents it? And the answer is of course that it is a nexus of relations between perceptible entities and events which can be grasped only in the ideal realm of human cognition, and yet is no less real for that.
A further problem with DNA-thinking is the idea that what happens now is programmed by something which happened in the past. 'Our fate is in our genes' thinks Watson.19 This shows the kind of concept of causality which is appropriate only to inorganic nature. The bullet moves impelled by a previous explosion. But life is not like that. It no doubt takes up what is there, but its fluidity transcends such narrow ideas of causality. The river of life flows round obstacles. Appleyard in the book already mentioned touchingly describes this from his own experience of how his niece lived her shortened life to the full despite the fate prepared for her in her genes. And such destiny events are in their turn an opportunity for transformation for all those caring for the sufferer.
So in contrast to whatever 'corrosive'20 powers have been dreamed by reductionists into Deoxyribose Nucleic Acid to dissolve away any idea of higher order, of a true human essence or entelechy, we can see that the DNA is of secondary importance in forming the human being. It is no less necessary for that, as are formative factors such as nourishment, warmth and the social context. Indeed, disturbances in the DNA are often associated with dramatic changes in the form and function of the human being, an aspect we shall come to later.
Discussing illness in the context of genes soon leads us into the nature versus nurture debate, or in this context to trying to establish whether an illness is genetic or environmental. But a science of the human being, anthroposophy, finds neither of these poles of presumed explanation or causation adequate. It follows from the foregoing that a third, most important, factor is involved, namely the incarnating individuality in relation to which the admittedly indispensable conditions of genes and environment are subordinate. Man is a master of his heredity, not it's slave.21 Anthroposophical medicine recognises not only the physical body and ego, but also the subtler 'bodies' working in between them into the physical. Therefore in anthroposophical medicine, the origins of illness are sought in how harmoniously or otherwise the ego mediates its use of the body through these subtle bodies.22 Too strong or weak in-forming by the ego or a predominance of either of the intermediate bodies can leave its mark on the physical and is manifested as illness. When 'mere heredity prevails', it is a sign of illness the ego is shirking its task.23
Neither does an anthroposophical approach ignore the importance of the genes. Indeed, we have already seen how the genes are an essential part in an evolutionary-karmic process and are not just an accident that happens at conception. However, I believe that placing so much hope for the future of medicine on knowing the human or the individual's genome is a big mistake. Tony Blair hopes that it will advance the treatment of cancer. But a recent study of medical records of 44,788 pairs of twins born in Sweden, Denmark and Finland since 1870 concluded that overall, if one identical twin had cancer, his or her sibling had a less than 10% chance of contracting the same disease.24 Clearly, this statistic alone shows that knowing genomes is not going to solve the cancer problem for most people. Incidentally, the authors concluded from this finding that environmental factors are of overwhelming importance in the aetiology of cancer, but in the light of comments in the previous paragraph that would be too simple a conclusion. Taking a broader perspective, we can say that cancer occurs, where the formative influences of the higher members of the human being, are no longer able to regulate the aspect of the body responsible for effecting the living vegetative processes (cf. note 17). This manifests as unformed prolific growth in a tissue. And this embraces the fact that environmental factors such as chemicals and electromagnetic radiation (e.g. microwaves) can oppose the working of normal bodily formative processes, leading to mutations in the genes. It is worth noting in this context that the HGP in the USA was initiated by the Department of Energy which has continued to contribute a major share of the funding. The US DoE's interest is in wanting fundamental genetic information about the human being for research on how environmental radioactivity, for instance from the nuclear power programme, might affect people via their DNA. We can also question how 'environmental' environmental factors really are. Of all living beings, man has the greatest ability to create his own environment. Consider the feat of taking an earth-like environment to the moon and back to support astronauts. That activity of environmental creation emanating from human ego-activity and desires affects individual and societal behaviour. This can result in excessive exposure to radiation or carcinogens from both the natural (e.g. sunbathing) and directly man-made environments, including substances ingested or inhaled. Here again is a way in which shortcomings in the higher activities of the human constitution create the conditions for disease.
One criticism made by a statistician of the Scandinavian twin study is that it was not possible to say if a particular case of cancer was entirely environmental or genetic.25 This facile criticism can be levelled at all genetic risk statistics. Already clinical geneticists can detect whether people carry in their DNA certain precisely characterised gene sequences associated with disease. Finding more of those sequences is an intended spin-off of the HGP. Screening for them will become a fast routine automated procedure in the near future. Already DNA micro-arrays or chips, coated with tens of thousands of different short DNA sequences called DNA probes can be dipped in a solution of a patient's own DNA. If a sequence is present which is a complementary match to a probe, it will stick to it through the tendency of the bases to pair (see Fig. 1). A suitable fluorescent marker and laser detection system 'reads' which disease-associated sequences are in the patient's DNA. But in many, if not most, instances the result will enable the clinician to tell the patient only that they have a certain statistical probability (or improbability) of getting symptoms of the associated disease. This life's-a-lottery approach, will say very little if anything about the susceptibility of the particular individual. Whereas pessimists will worry, perhaps becoming ill as a consequence, optimists will simply ignore the information,26 indeed, perhaps even have children in the face of a high risk of passing on the DNA sequence.27 However, even if this approach is looking in the wrong place for disease aetiology, the general concept in the hoped-for fallout of the HGP that medical treatment will be totally individualised cannot be dismissed out of hand. When medicine gradually realises that illness is intimately connected with individual biography and is meaningful in such a context, increasing individualisation of the study of the symptomology, even if only initially at the DNA level, will be a complementary part of the quest for a treatment. But the treatment, if DNA based, i.e. through gene therapy or pharmaceutical control of gene expression, risks remaining within the current paradigm of treating merely symptoms, as happened, for instance, when proponents of the germ theory of disease hit upon antibiotics. Put simply, this bottom up approach needs to be complemented with the top down approach for a truly holistic science and art of medicine to arise. But currently almost all the wealth available for medical research goes on bottom up approaches like the HGP.
Holtzman and Marteau, writing in the prestigious New England Journal of Medicine draw on a large body of evidence from genetics to argue that "the new genetics will not revolutionize the way common diseases are identified or prevented. Mapping and sequencing the human genome will lead to the identification of more genes causing Mendelian (see Box 1) disorders and to the diagnostic and predictive tests for them.28 But most of the human bodily form and function cannot be accounted for in terms of Mendelian inheritance, that is, the linking up of characteristics or traits which geneticists call phenotypes, abstracted from the totality of the organism, with associated inheritable markers called genotypes. Note that consistent with the foregoing discussion we do not speak of genes for or causing a disorder here, but of association. The gene, more correctly viewed, is one factor in an organism's environment, albeit its intimate environment, which along with other bodily substances, nutrients, warmth, light, its parents, society etc is essential for that organism to manifest. Amongst the bodily substances the imprinting of the form is not a monopoly of any specific substance. Of course, disturbing or accidental influences from any of the factors, including genes can impede full manifestation of the ideal form or type of the organism, or individuality in the case of humans. The association between a particular gene and its related disease can be stronger or weaker as measured by the statistical tests used in genetics. Mendelism works well for something like Huntington's disease which is due to a single, highly penetrant dominant gene. By high penetrance we mean here that if the gene is present, the observable characteristics associated with it, in this case a disease pattern, are highly likely to manifest. Furthermore, if the person affected has only one copy of the associated 'faulty' gene, i.e. on only one chromosome of the pair, in order for the disease to manifest the gene associated with it must be dominant. Holtzman and Marteau also challenge the notion that the HGP ushers in the era of genomic medicine by pointing out that in over 40 years since the molecular basis of the heritable disease sickle-cell anaemia was discovered, no definitive treatment for it has emerged. They point out that many combinations of genes strongly associated with disease, environmental factors and behaviour could all lead to the same pathogenic effect. And we can concur with this from our view that disease or its absence is administered at a much higher level in the organism's hierarchy than at the level of 'external factors', amongst which we must include genes. And that higher level, human individuality working alone or socially with others creates the differences in lifestyle, environment and social structure to which Holtzman and Marteau attribute the lion's share of the conditions for disease as compared with genetic differences. And as regards our early years, it would not be stretching the imagination to regard our surroundings and the people in it as part of our inheritance.
If neither genomic medicine nor knowing what it is to be human are to be likely benefits to humanity from the HGP we can safely conclude that it would have been better to spend the billions on developing a holistic approach to understanding disease in parallel with educating to change lifestyles as well as reducing social deprivation and environmental pollution. But this kind of investment in the future would mean a widespread change in the mind set of a society that has largely accepted the DNA myth and raised it to the level of a cultural icon.29 Such a change would take many decades to effect, rather than the 10 years for the technical fix of the HGP. We must now watch the project reach its conclusion before the limitations of its approach come home to its proponents, as indeed we had to do with atomic power. Meanwhile, I'm with Tom Shakespeare when he says 'William Shakespeare still has more to tell us about human nature than genomics'.30
David Heaf is UK co-ordinator of Ifgene the International Forum for Genetic Engineering. (Ifgene home page: www.ifgene.org).
Acknowledgements: The author wishes to thank his wife Pat Cheney for her help with the text; Rudolf Saacke for his bibliographic search on his electronic database of the Rudolf Steiner Gesamtausgabe and Don Powell of the Sanger Centre, Cambridge for advice on the HGP.
Notes1. New Scientist, 1 July 2000, p4. www.newscientist.com 2. Wellcome News, issued by the Wellcome Trust, Issue 20, 3rd Quarter, 1999, pp14-15. 3. Eric Lander, the Whitehead Institute, quoted in New Scientist, 1 July 2000, p4.. 4. New Scientist, 20 May 2000, p16 5. Darnovsky, M. & Hayes, R. (2000) Techno-Eugenics Email List newsletter, No. 10, August 4. Subscription enquiries to email@example.com. 6. Wellcome News, issued by the Wellcome Trust, Issue 23, 2nd Quarter, 2000, pp2 & 8/9. 7. Mike Dexter, Wellcome Trust, quoted in New Scientist, 1 July 200, p4. 8. Annas, G. J. & Elias, S. Eds. (1992) Gene Mapping Using Law and Ethics as Guides. Oxford University Press. (Enhanced proceedings of a workshop, January 1991, Bethesda, Md.) 9. Appleyard, B. (1999) Brave new Worlds: Genetics and the Human Experience. HarperCollins Publishers, London. Review 10. Steiner, R. (1886) A theory of knowledge implicit in Goethe's world conception. Anthroposophic Press, New York. 1978
11. Steiner, R. & Wegman, I. (1925) Fundamentals of therapy. An extension to the art of healing through spiritual knowledge. Rudolf Steiner Press, London, 1967.
12. Watson, J. D. (1989) quoted by Susan Lindee in The Future of DNA, Wirz, J. & Lammerts van Bueren, Eds. Kluwer Academic Publishers. Chapter 3: The cultural powers of the gene identity, destiny and the social meaning of heredity. www.ifgene.org/confer.htm
13. Steiner, R. (1910) Macrocosm and microcosm, 11 lectures, Vienna, 21-31 March, lecture 5. Rudolf Steiner Press, London, 1968.
14. Lawson, D. (1995) All you need is life. The Spectator, 17th June.
15. Heaney, S. J. (1992) Aquinas and the presence of the human rational soul in the early embryo. In Abortion: a new generation of Catholic responses. Chapter 3. Heaney, S. J. Ed. Pope John XXIII Medical-Moral Research and Education Center, Braintree, Mass.
16. Watt, H. (1998) The Origin of Persons. In Identity and Statute of Human Embryo. Proceedings of the 3rd Assembly of the Pontifical Academy for Life, Vatican City, 14-16 February 1997. Correra, J de D. V. & Sgreccia, Eds. Liberia Editrice Vaticano.
17. Weihs, T. J. (1986) Embryogenesis in myth and science. Chapter 9. Floris Books, Edinburgh. The spirit-soul elements called by Steiner 'ego', 'astral' and 'etheric', correspond to Thomas Aquinas' concepts of rational, sentient and vegetative souls respectively.
18. See for instance Vines, G. (1998) Hidden Inheritance. New Scientist, 28 November, pp27-30. www.newscientist.com19. Watson, J. D. (1989) Ibid.
20. Van der Wal, Jaap (1997) Back to the future towards a spiritual attitude for managing DNA. In The Future of DNA, Wirz, J. & Lammerts van Bueren, Eds. Kluwer Academic Publishers. Ch. 5. www.ifgene.org/confer.htm
21. See for instance Popplebaum. H. (1977) New light on heredity and evolution, St George Publications, Spring Valley. Popplebaum takes a phenomenological approach to heredity which generally stands the test of modern developments in molecular genetics, but the emphasis of some of his conclusions would need revising in the light of some more recent discoveries.
22. Bott, V. (1978) Anthroposophical medicine. An extension of the art of healing. Rudolf Steiner Press, London. The subtle intermediate bodies referred to are 'astral' and 'etheric' (see also note 17).
23. Popplebaum, H. Ibid.
24. New Scientist, 22 July 2000, p10 reporting on Lichtenstein, P. et al. (2000) New England Journal of Medicine 343, July 13, 78-85.25, Richard Peto, quoted in New Scientist (see note 24).
26. Bascou, J. (1999) Les progrès de la génétique: un défi pour notre temps. Première partie: L'entrée dans l'ère du génie génétique. Association de Patient de la Mèdecine d'Orientation Anthroposophique. Bulletin no. 38, Summer 1998, pp3-10. www.ifgene.org/artsf.htm
27. Shakespeare, T. (2000) My two children and I share a genetic abnormality. So why does this week's scientific milestone scare me so much? Daily Mail, 28 June, p12.
28. Holtzman, N. A. & Marteau, T. M. (2000) Sounding board: Will genetics revolutionize medicine? The New England Journal of Medicine, 343(2), pp141-144.
29. Nelkin, D. & Lindee, M. S. (1995) The DNA Mystique. The gene as cultural icon. Freeman, N.Y.
30. Shakespeare, T. (2000) http://www.sanger.ac.uk/HGP/draft2000/commentary.shtml (Tom Shakespeare is the director of the Policy, Ethics and Life Sciences Research Institute, Newcastle University and was born with a genetic abnormality called achondroplasia he is 4ft 5in high.)
© David Heaf, 14th October 2000
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