Editors: Norio Fujiki, M.D. & Darryl R.J. Macer, Ph.D.
Professor, RenŽ Descartes University; Member of the European Parliament, Paris, FRANCE.
I learned in Kobe during the last presentation by Victor McKusick, chairman of the HUGO Ethics committee, and from my co-chair, Nancy Wexler, some interesting ideas and especially "The gap between what we think we know and what we really know".
This is true for scientists and patients as well. Scientists have a faculty to anticipate their observations in order to insure the progress of their works. Patients naturally anticipate the quality of the results because of their confidence in the relief of suffering. Thus, both physicians, directly confronted to the patients and their families, and journalists dealing with public opinion, must draw a particular attention to the fairness in the use of genetic information.
Thanks to the role of the MURS, chaired by Professor Jean Dausset, which informs clearly lay people to avoid misuse of science. Another gap exists between the new possibilities of diagnosis in genetic diseases and the success in the treatment i.e., gene therapy. Lastly, a gap exists between the prediction of multifactorial polygenic diseases and the occurrence of such a disease in the parents of a foetus before birth. There is a long way between gene localisation, gene sequencing, mutation identification, diagnosis, treatment and, at last, the cure of the genetic disorder.
Physicians and journalists have an obligation to present the reality and to discuss frankly with the persons involved, or with the public opinion anxious to knowing more about the results. The scientists, for their own part have to stick to a rigourous and objective scientific approach. This will be presented in the next lecture by Prof. Fujisawa during his talk on Science and Ethics.
I would like now to present the problem of gene patenting in such a specific context. Forty years have elapsed between the discovery of the DNA double helix by Watson and Crick and the award of the Nobel Prize for chemistry to Mullis for the discovery of gene amplification. The period has been a rewarding one for the development of research on the human genome, the components of which have now been located on the chromosomes and chemically identified in the form of nucleotide sequences.
We are now at a crossroad and we must know where do we draw the line regarding research on gene patentability and use of the patented products. Although there are still some areas of obscurity, the chemical sequence of several thousand genes has been identified, thanks to human genome research programmes. The work has been carried out in Europe and particularly in France, as well as in the United States and in Japan, particularly thanks to the efforts of HUGO.
The gene has two vital functions: the transmission of hereditary material to descendants and induction, through the transcription of a specific synthesis, expressing a precise function.
The commercial potential of the use of genes and their nucleotide sequences is obvious, particularly in the preparation of human products such as insulin, growth hormone or antihemophilic factors, and for developing diagnosis kits for genetic diseases and prenatal diagnosis and ultimately gene therapy. In view of the high commercial stakes, and in the absence of an exact knowledge of the function of all nucleotide sequences identified from the human genome, we are faced with the problem of how to protect such sequences while ensuring that ethical rules are respected. These rules are founded on the need to recognize the integrity of the human body and the identity and autonomy of individuals.
The application by Craig Venter and the NIH in the United States for patents on 3500 nucleotide sequences without any known function, so called 'naked genes', is difficult to justify since no precise claim has been made for each sequence. In the UK and Japan, governments or firms, despite of the recommendation by the scientific community, adopted the same position for a partial part of their results. The scientific community proposes that efforts should be made to find other solutions.
In my presentation I shall discuss: the ethical principles; the difference between discovery and invention; the need to recognize and protect human intelligence; the respect for the integrity and identity of the human being and his components; with a view to formulating proposals.
The concept of ethics goes far beyond the individual or professional moral code; it involves defining the place occupied by the human being in relation to his activities. Ethics could be defined as the moral code of action. How far can the human being go to defend himself against adversity and to maintain his autonomy? How should advances in science and medicine be used to combat disease, without encroaching upon personal freedom? Where does a medicine of personal convenience begin? How far should society go in exercising its power to constrain, while remaining at the service of human beings?
Human bioethics are founded on three principles:
1) respect for human dignity, i.e. respect for the human being and the identity of the individual;
2) respect for knowledge, and in particular intelligence and the scientific approach;
3) a rejection of disproportionate financial gain and respect for fair reward, whether in terms of payment or social recognition.
Learning, the instrument of knowledge, allows man to take possession of what he is and of his surroundings. Knowledge requires intelligence and intuition; it is for human beings a means of discovering the universe and invent its own modalities of expression. These may be languages, or software as tools or instruments ... as one part of the expression of his own identity. The process of discovery leads man to identify natural laws, mechanisms or objects which already exist independently of human beings.
Invention on the other hand is the process whereby humans can construct new elements that they can use. Invention is the result of human ingenuity and know how. Under these circumstances, no one can have the right to monopolize a discovery, as every discovery is part of the natural order to which human beings themselves belong. Human beings must treat any discovery with an attitude of humility rather than one of ownership.
On the other hand, any inventive process requiring intelligence can be claimed for ownership and expected for a fair reward - it is this principle which is behind patent law. According to No‘lle Lenoir, "the patent was initially regarded as a form of social contract concluded between the inventor and society. Society protected the inventor by guaranteeing him a reward for disclosing his invention and, in return, the inventor agreed that free use could be made of his invention".
The first statute of the inventor was adopted in Venice in 1474, followed by the first patent laws enacted in the United Kingdom in 1623 (Statute of Monopolies), in the United States in 1790 and in France in 1791. Since then, the industrialized countries and most of the developing countries have adopted patent legislation which has become increasingly complex.
I shall confine myself to the three main criteria governing patent legislation: novelty, inventiveness and industrial applications (or more broadly, 'utility' in the United States) insofar as these can be demonstrated and are not simply speculative.
The patent recognizes the inventor's role, ensures that he is fairly rewarded and prevents any misuse within the framework of the patent. The patent is ethical insofar as it recognizes the value added through the exercise of the intelligence or ingenuity of the human being. But the patent offices have not to pronounce themselves on the ethical value on the invention. The use of the limitations by public order or moral must be done very carefully. It has been recently proposed by the "opposition division" of the European Patent Office to take account of the horrific or outrageous aspects of some inventions. This gives a better opportunity to escape arbitrary and subjective positions for these experts. The use of inventions protected by patent is probably the area in which the greatest ethical problems arise, in that market factors come into play. This area concerns the industrial exploitation of patents with a view to their commercial use and this commercial gain.
The problem is all the more complex because we have a situation in which ethical principles are confronted with socio-cultural developments and purely economic considerations. In the light of this, I have a number of propositions to put forward.
The human genome cannot be patented as such, nor can its components. This is true not only for the human genome but for those of all living creatures. Identification of the genome, and of the genes of which it is made up and of the nucleotide sequences which describe the composition of these genes, constitutes a discovery. In a specific sociocultural context, the genome is responsible for the transmission of inherited characteristics. This gives the identity to the individual. It explains that in the organism, the gene occupies a unique position far more different than its function of biochemical machinery involved in the transcription mechanism for the synthesis of specific products. The genome cannot be patented any more than a natural living being can be.
In addition, the human body (and its component parts) cannot be regarded as an asset, it cannot be marketed and hence cannot be a source of financial gain. Despite the fact that society inevitably remains hierarchical, slavery has been abolished forever. Whereas the donation of an organ is probably the highest form of compassion towards the sick, the traffic in organs would lead to a resurgence of slavery, which must be resisted with determination at international level.
On the other hand, the use of the function of a gene or of a DNA sequence as part of an inventive process which is new and useful may give rise to a patent. It is in such a context that the first patents concerning living matter, which had been genetically modified, were granted on the grounds of the progress in genetic engineering: Chakrabarty case (1980), following the discovery of plasmids used in bacteria to decompose components of oil.
Under these circumstances, the problem facing us can be put very simply. On the one hand the functions of the gene or the nucleotide sequence are known. In this case patenting is possible, provided that the claim relates to its use in an inventive manufacturing process which is new and can be applied. On the other hand, the function is not yet known and patenting is not possible : it is necessary to find out an other mean of protection of intellectual property.
Referring to the first case, it has thus been possible to patent the use of the human insulin gene or the antihemophilic factor gene, with a view to obtaining pure products which can be used to treat diabetes or haemophilia. In the second case, the patentability of genes or gene sequences with no known function raises problems of a very different order. Although no biological property has yet been identified, these partial sequences may be recognized as having the potential for industrial applications or uses. For example, the use of short DNA sequences could be envisaged as a nucleic probe or physical marker in the mapping of a genome.
In principle, patent law cannot apply to such partial DNA sequences. Institutes and scientists should be thus tempted to protect their intellectual property by keeping their results for their own use. Any obstacle to the free movement, or exchanges of data relating specifically to such sequences, will impede scientific progress. It is therefore necessary to protect DNA data banks, for instance, by devising a signature process specific to each sequence.
Copyright law is probably not suitable since it primarily protects reproduction and not the use by a third party. Something more akin to the legal systems for the protection of software might be more appropriate. Assimilating genetic sequences to chemical molecules would probably be a quicker way of arriving at a system of protection, particularly since, alongside natural sequences, artificial nucleotide sequences can now be generated by computer, as for drug design. The new and inventive character of the latter is obvious. A genome sequence could be regarded as a chemical product and this would require it to be treated as such from the point of view of industrial property.
The main problem would then be to prevent patents overlapping. One of the ways of doing so, suggested by Professor Pierre Louisot, would be to rule "that the patented gene was being patented only because it formed a part of a whole, made up of a chain of production. It is thus considered as a patented finished product, but its informative contents would remain open to all without reference to the initial patent".
This would require us to examine, as rapidly as possible and at international level from the outset, the ways of protecting intellectual property relating to research on the human genome.
This would in no circumstances minimize the real ethical problems linked to the use of results of research on the human genome, and in particular the consequences of the industrial and commercial use of patents granted judiciously. A Patent is not a licence. A Patent does not give the right for commercialisation. The use on the market has to be controlled by the law and applications are of the judge responsibility. This implies the respect of confidentiality, the freedom of choices and the enhancement of the modes of consent as well as the limitation of the human genome research to the fight against diseases.
The scientific responsibility is thus involved by human genome research. It is necessary not to interfere with the progress of science and to promote innovation and creativity. But the different States must be attentive to the use of the scientific data. The product of intelligence must be protected. Any justified claim must be protected through patents, but the use of these patents has to be looked after by the governments taking into account the ethical, social and legal aspects of the use of the discoveries on the human genome. The governments are also involved in the financing of research. And works which are threatening humanity should not be financed.
Thus a number of general principles emerge: 1) the need to respect human dignity and the identity and autonomy of the individual; 2) the need to recognize science and the scientific world and not to obstruct the progress brought about by scientific research; 3) the need to take action against the risks of disease, while rejecting a medicine of personal convenience.
The role of scientists is to advance the frontiers of knowledge and of science, but the use of such knowledge is not solely the responsibility of scientists: it is up to society to fulfil the expectations of the men and women who make up that society. And this, it seems to me, is the responsibility of individual States and will depend on the socio-cultural context of each of them.
Respect for ethical rules is necessary; respect for the identity and autonomy of individuals must be guarantied in the same way as recognition of intelligence and of intellectual property.
Research on the human genome will lead to genetic testing, prenatal diagnosis, gene therapy and to research into predisposition to disease. Even if it is vital to make allowances for socio-cultural developments, respect for the broad ethical principles will prevent different countries outbidding each other in a world dominated by economics and industrial competitiveness. Thus every government has a duty to take account of the ethical, social and legal aspects of the scientific progress, in the frame work of a new relationship between science and society.
It seems necessary to distinguish: science and technology, patents, and use and commercialisation. Science and technology is a consequence of knowledge and know-how. They are the consequences of human intelligence, it must be recognized as a factor of progress for humanity. Patents recognize the human intervention for the realisation of a process and, or a product; The production and unfair use of which is prevented by this patent. The criteria are novelty, inventiveness and utility. Use and commercialisation is not only possibility of utilisation but also usefulness. Patents should be the exclusive responsibility of patent office. But the patent office should be responsible for nothing but the patent. Patent Offices are not in charge of ethical aspects but only of the protection of intellectual and industrial properties.
Human bioethics is involved in the the two other aspects. Science and technology cannot be developed for the only respect of science and ingenuity.
Scientists are responsible for science by their own but, if they seem to push their ideas forward too far, the society has to put them in the picture. The control of financing is a useful mean. Thus, an ethical way of thinking is necessary for science and scientists as well as for engineers. Utility should not be limited to utilitarianism and the use of the results of science and technology should be more and more controlled by the society. This is the role of national laws or national guidelines taking into account the social cultural aspects. This has to be done in the respect of general bioethics principles, internationally accepted and related to human value. A medicine of personal convenience, information to insurance companies or employers are risks that cannot be ignored. Hence , I insist for the need to rules of confidentiality, to respect independent and informed choices and for limiting the use of genetic testing to combating disease.
Today, advances in science and medicine make it necessary to lay the foundations for a new social contract failure to do so will not only undermine the relationship of trust between doctor and patient between scientists and public perception of science but, more broadly, that between man and society. It might thus seriously undermine the very society in which we live and lead to conflicts whose consequences are unpredictable.