Darryl R. J. Macer, Ph.D. Eubios Ethics Institute 1990
There are many biotechnology companies established, for instance at the beginning of 1989 there were more than 84 companies in Japan alone making and testing products made by GMOs (FDA 1989) and several hundred in the USA. Most governments are promoting the use of biotechnology as it covers huge markets. Almost all the notable US biologists researching in the area are working in some way with businesses. Genentech's Herbert Boyer tops the list of former University professors turned millionaires, with an estimated fortune of US$ 88 million (Fowler et al. 1988). This could make it very difficult to find really independent expert advice.
Different Universities have decided on various proportions of commercial proceeds to share with inventors. The most generous policy in this regard is that of the University of California which allocates a 50:50 split at all levels of income (Weisbach & Burke 1990). This is certainly a strong incentive for researchers to obtain intellectual property rights, such as patents. The basic research may be channelled to commercial organisations. This technology transfer has been the cause of the establishment of the multitude of companies. The collaboration between University research and biotechnology is at a high level in the USA, and the industrial contribution to academic research is four to five times greater in biotechnology than in other fields. Part of the reason is that there is still much basic biological research required before we understand the details of gene regulation, which is necessary to be able to exploit genetic technology fully.
During 1988 at least 24 US biotechnology companies filed for bankruptcy protection. Within ten tears it is expected that half the 500 US biotechnology companies will be gone. This is occurring long before the companies have refined their processes or have come up with any products. In fact the delay of several years before there is any product is one of the important causes of bankruptcy. In a survey conducted by Ernst and Young in the Wall Street journal (Gupta 1989) most firms were going to have to reduce their spending levels within the next two years. The key concerns are summarised in Table 10-1.
One of the main reasons is that they have run afoul of public fears, regulation and patents confusion. Few companies expected the negative public reaction. The regulations are also complex. It takes two months to prepare a study for the EPA, which typically takes 5-6 months to review it and approve a field test of a GMO. If any information is left out the process starts again. In a 1990 survey of U.S. researchers and institutes, there were a number who were ready to field test a GMO but because of uncertainty over regulations had not applied to release the GMOs (Ratner 1990).
Another concern that is important is the fear of legal claims. The development of new contraceptives in USA has been greatly inhibited by this, as will be discussed in chapter 11. In the medical field the financial damages have become astronomical. This is also a concern for the use of GMOs. When they are introduced as foodstuffs there should not be any novel compounds in the food, and they are of negligible risk, if approved safe. In the case of vaccines, there is more risk as the vaccine may be of novel structure. Despite the great success of vaccines in combating disease, companies are scared out of research by product liability fears. It has been suggested that we should immunise the manufacturers from these claims so that they will perform such research and introduce useful vaccines (Earley 1990).
Americans are worried that the multitude of small companies could be bought for US$ 6 billion, when the potential is for their sales to be worth much more. There are a number of companies that have been taken over by multinationals, and a few examples are given in Table 10-2. In some of these takeovers the results have been more positive than expected. This is because the increased funds allow freer research into longer term projects involving more basic research, because this is less immediate demand for financial success (Barianga 1990). In addition to the research delays, and regulatory delay, there are long delays for consideration of intellectual property rights. There are about 7,000 biotechnology patent applications awaiting approval in the USA, and it may take 5-6 years to resolve the backlog (Naj 1989).
Concern Most Crucial Issue %
Finance
Limited R&D funds 19
Expensive Capital 13
Other financial 4
Government
Complex regulatory environment 14
Patents 5
Reimbursement unclear 2
Liability insurance 1
Operational
Product pricing 4
Other marketing 4
Others have R&D lead 3
High manufacturing costs 3
Attract/retain key people 3
Product lives too short 1
Strategic
Lack of marketing partners 11
Other strategic 1
Competitive
Competition from estab. industry 8
International competition 2
Other 2
Company; Year Founded; Acquired by; Date; Price; Employees
DNAX; 1980; ScheringPlough; 1982; $29 M; 150
Hybritech; 1978; Eli Lilly & Co.; 1986; $375 M; 800
Oncogen; 1983; Bristol-Myers; 1986; unavail.; 209
Genentech; 1976; Roche; 1990; $2.1 B; 1770
GenProbe; 1983; Chugai Pharm.; 1989; $110 M; 166
In 1989 a new commercial product appeared in the United Kingdom, consisting of pairs of frozen beef cattle embryos which are being sold at US$70 a pair (including implantation) to dairy farmers. They are able to implant the embryos into their dairy cattle so that beef calves are produced, which are worth more money, yet maintain the requirement for dairy cows to have a calf each year to maintain the high milk production. The initial annual production will be 50,000 embryos, made by collecting cow ovaries from the abattoirs. From each ovary about twenty useful eggs is obtained, which are subject to IVF. A cow has a 70% chance of becoming pregnant, about the same as the rate for artificial insemination (Newark 1988).
There is a movement in society that wants to refocus attention on less economically-orientated goals (Hallen 1990). If they do become politically powerful, as the Green party; in Europe has become, then the situation will change. There is also a philosophical movement against the rapidity and extent of changes to society, which is opposed to the use of genetic engineering. This reaction is stronger against corporations that are seen to be trying any method to make money without considering other factors. This criticism is justified against some corporations, and will change only if a greater amount of responsibility is felt by them. It may also change due to public reaction which will reduce profits, as is being seen in the consumer reaction against using bBovine somatotropin; in cows.
People are more suspicious of commercial companies than independent groups. As mentioned before, the OTA survey in the USA of public attitudes to GMOs found that people are more likely to believe environmental groups than companies. This trend may be reflected in the lower public credibility over statements about environmental risks made by commercial scientists compared with government scientists, in the New Zealand public attitude survey (Couchman & Fink-Jensen 1990). People are also probably less supportive of field trials of GMOs if conducted by commercial companies than if they are performed as small scale experiments by University researchers (OTA 1987b).
Increased yields of agricultural products will mean that farmer subsidies for excess production may need to be changed. The average yield increase per year is 1-2%, however biotechnology may allow greater increases. The present production levels have led to a variety of "food mountains", or "milk lakes". Governments have attempted to control this. There will be further exacerbation of these problems so that the area of land required to grow some crops will substantially decrease. This in itself may be environmentally advantageous, but many individual cases will not be. This will change the structure of farming. The first test is the use of BST to increase milk production. It will favour large scale farmers, as discussed later. The way that small farmers can compete is by shifting to higher profit products. For example if BST-milk is labelled as such, which it should be, then small farmers can market their milk to the consumer preference for more "natural" products.
It has been estimated that should BST be used in the USA, by the year 2,000, the U.S. dairy market should require 30% fewer cows, and 51% fewer dairy farms, 195,000 fewer dairy farm employees, and 9 million fewer acres of land for dairy feed production (Banville 1988). In other sectors there may be a shift in farming practise, but it is also inevitable that there is less land, and hence less farmers, required (Kimbrell & Rifkin 1988). Productivity is a ratio of output to input, and it is the increase in productivity rather than production, that is the goal of applying technology in developed countries.
As productivity is increased there will be less land required for agriculture. This may mean fewer farmers. There are already major differences between countries in the size of farms. Anyone who has travelled across the vast farming land of North America must have been impressed with the size of the farms, as will anyone who travels through the countryside of Japan with the tiny fields among the houses. There are obvious reasons for very different production costs, aside from any differences in wages and living standards. There must be questions about whether the new crops, or animals, will be best suited for large scale farming, or will also be used by small farmers. Society must ask whether it wants to subsidise small farmers and retain their existence, or decide not too, with the social disturbances as the rural community disappears. Where will the limits be placed. There is a limit to this, and productivity is not the only pursuit. When you walk in the big cities of the world and see the social problems, you must ask is it better for people to live in smaller rural communities or not. A few people reject modern urban life and return to communes in the countryside, this is an expression of this idea. We must think in terms of broad social policy about the limits to our development of a modernised world, while also acknowledging the benefits to people that can come from new technology. Perhaps we should develop varieties that can be produced easily by smaller farmers, rather than in the larger farms. This possibility is presented to us by biotechnology, we must open our eyes to alternative ways of pursuing it. We should look at utilitarian ethics, and consider the greater loss of preferences to those who lose their jobs, and vocation, versus the greater number of people who have relatively little to lose from the decision not to switch more to big farming enterprises. We should support the so-called family farms, though we do not need to use the agrarian argument, that farming is a prefered occupation, rather it is protecting people in one particular lifestyle.
This food surplus will have broader ramifications. As food production in developed countries increases, there will be greater surpluses to dispose of. We can hope that benefits are shared by developing countries who, because of their high population growth, will have ever greater shortages of food. The economic system will thus be challenged, affecting much more than agricultural policy.
The initial beneficaries of increased use of technology will be the businesses that receive the royalties for the technology used. In the case of biotechnology they may have invested considerable sums of money in the research, so if we want further research to continue there must be some renumuration of the companies investment. The farmers may be beneficaries of the new techniques if it is cheaper to produce, and less labour intensive. The consumers are also beneficaries as the price of the products falls because of cheaper production costs (Madden & Thompson 1987). A local community where the farming is being conducted also benefits, and conversely a community which does not use higher productivity techniques may suffer. The national economy of a country may also benefit .
One concern is over patenting laws. Patents for individual molecules are held by different genetic engineering companies, similar to patents obtained for pharmacological drugs. Of all the biotechnology patents issued in the USA in 1989, about half were for drugs and health care products. The others were primarily for agricultural and environmental cleanup products. The first patent obtained for a living organism was obtained after the court case Diamond v. Chakrabarty in 1980 (Curry 1987). Industrial competitiveness leads to secrecy, and results may not be published until the patentable results are obtained. The closing of results from other workers is against the principle of scientific openness. On the positive side, the financial interest has created more funding for research (Yoxen 1987), and faster overall progress in research in these areas has been the result of the intense research efforts.
Patents can generally be sought either on products or processes used to manufacture the product. It is easier to obtain a process patent, but it has been harder to prove that a competitor is using your process, as access to their production facilities may be restricted. The US Process Patent Law, effective from February 1989, shifted the burden of proof in process patent cases from the company with the patents, to the importer of the competing product. The importer must prove that they are using a different process. There are still differences between the systems used in Europe, USA and Japan, as well as other countries (Cook 1989). For example, under the old US patent system inventors can apply for US patents any time up to a year after the disclosure of their finding (e.g. in a scientific journal), but in Europe or Japan, prior publication invalidates the claim. It is likely that this grace period will be removed, so that many more research results will be first published as patent applications, before they appear in scientific journals (Hodgson 1989b).
During 1987 the US Patent and Trademark Office made the following announcement: "The Patent and Trademark Office now considers non-naturally occuring non-human multicellular living organisms, including animals, to be patentable subject matter ...". The conflict between economic advantage and moral objection is further highlighted in the granting of animal patents. Some animals are now under patent, the first patent to be issued for animals, applies to all non-human animals made containing an activated oncogene inserted by genetic engineering techniques, and was based upon one such mouse made, later called "Oncomouse" (Editorial 1988) It was U.S. Patent number 4,736,866 (Clark 1989). These animals can be used as more suitable research "materials" for testing sensitivity to carcinogens. Du Pont, the licensee of the Harvard patent, is taking orders and selling the mice at US$50 an animal. The question of the patenting of animals is very contentious, and there have been some major studies on it (OTA 1989). After the Oncomouse patent, 29 congressmen sent a letter to the US Patent Office labelling the decision as "arbitrary and capricious". Both the Senate and the House of Representatives have considered bills calling for a moratorium on patenting animals. Over forty other applications were held up while policy decisions were made.
The legal situation varies between countries, but it appears that there will be an increasing number of animals under patent in the United States. The OTA Report said that existing regulations can be adapted for most of the practical considerations of animal patenting, such as whether farmers should pay royalty fees for breeding patented livestock. There had been earlier attempts to obtain animal patents, but they were hampered by the lack of a precise definition of how to repeat the procedure. The claim of the "Oncomouse" patent is worded: "A transgenic non-human mammal all of whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal, or an ancestor of said mammal, at the embryonic stage." It is precisely worded, and based on a genetic description, which is the reason it was accepted (Clark 1989). The first step in the creation of such an animal is easily definable, so that a chance mutation on a farm is not going to violate the patent. The deposited item is actually the plasmid used in transformation, which is sufficient, rather than embryonic cells. Classically bred animals might be protected by animal variety rights legislation, but it is unlikely that they could be patented.
There have been several pieces of legislation proposed in the USA to regulate animal patents, ranging from a ban on them, to a system with similarities to plant variety act legislation (Czarnetzky 1988). Under the Animal Patent Act, a patentable animal is an organism with one or more characteristics that are distinct from all other known animals. The US House of Representatives passed a bill in 1989 which, if enacted, bars the granting of patents to humans and provides for a farmer's exemption from patent infringement with respect to transgenic farm animals. The only standard exception to the US Patent Office's "anything goes" interpretation of the law on the patentibility of animals lies in the reluctance of the US Patent Office to allow a claim to an animal broad enough to encompass human beings. The Commissioner has asserted that the "grant of a limited, but exclusive property right in a human being is prohibited by the Constitution" (Armitage 1989). A legal point that has not been defined is what is the definition of a human being, in the case that animal-human hybrids are made (Fishman 1989).
There are two basic approaches to applying patent law to biotechnology inventions. In the USA the normal patentibility criteria shall apply, that is the invention has the attributes of novelty, non-obviousness, and utility, and the invention should be deposited in a recognised depository. The second type of regulation is to apply special criteria. While a country may accept the first type of criteria, some countries have specifically excluded certain types of invention. This is the case in the Europe Patent convention, and in particular countries such as Denmark which have stronger worded exclusions.
According to European Patent Convention Article 53(b), microorganisms are patentable, but "plant or animal varieties or essentially biological processes for the production of plants and animals" are expressly barred. Since the animals need to be reproduced by a natural biological process, reproduction, then they can be regarded as unpatentable. However, property rights have long been recognised for breeding animals such as prize bulls and racehorses. There are still signs in 1989 that moves are underway to make animals potentially patentable in Europe, even though the European patent office in Munich has turned down the application for a European patent for Oncomouse. It is possible to interpret the clause 53(b) in a different way, and the OECD has recommended that this be done. In this case a new plant or animal would be considered a new variety only if it was explicitly described as such (Dickson 1989a). There is public rejection of the idea in some countries, and there is an explicit law in Denmark against animal or plant patents. The European Council has drafted a directive to change the laws on biotechnology patents. The draft declares living matter is no reason for nonpatentibility. Animal or plant varieties will not be patentable, but the insertion of a particular segment of DNA into the genome of a seed will still be patentable even if the resulting new plant constitutes a variety and is not itself patentable (Whaite & Jones 1989). At least ten countries permit animal patents, including Japan and Canada, and another 53 have not prohibited the granting of patents (Lesser 1989).
It is important that patenting protection does not prevent the widespread application of important new strains. This includes both those organisms important for scientific research, and the increasing number of new agricultural varieties that have been made. Many companies are involved in the work solely for the fortune that they will make from using what are essentially natural genetic resources, which are merely moved around. There has to be some limit to how the patents are enforced, especially in areas such as agriculture where companies could be seen to be making a profit from world food needs. However, these are conditions that could be practically solved, and similar problems have been dealt with plant variety licensing in many different countries. A recent OECD report highlights the finer details of competition policy, and the law will need further development in the area of biotechnology patents. Monopolies on patents are discouraged, but there will be complications with patents and agreements with farmers (Phillips 1989).
Public Attitudes to Patenting
There is an unresolved ethical question whether corporations have the right to create and patent new forms of higher life for profit. Just because courts in some countries support the patenting, it does not resolve the ethical dilemmas. In the USA, the constitution, a document 200 years old, is applied to this question and used to justify the patenting of lifeforms. This does not necessarily provide any ethical answer to the question. It may be consistent with existing capitalistic ideas, and support inventors to encourage creativity, but this does not solve the underlying question. The question is whether the limit of applying patents has been reached with the case of animals, or will the limit be placed at humans? The opponents of animal patents include animal rights groups, and people who have a high inherent respect for animals such as religious groups.
The public attitudes to the patenting of different types of things, including living organisms was measured in New Zealand. The results are presented in Table 10-3. 90% of the public had heard of inventors being able to obtain a financial reward through patents or copyright. Those who had heard of patents or copyrights were asked if they agreed whether patents should be obtainable for the five classes of items (Couchman & Fink-Jensen 1990).
The survey of the general public was conducted with face-to-face interviews, the rest were written questionnaires among different occupation groups. Of those people who had heard of patents, the question was asked, how many agreed that patents should be obtainable for the following areas:
Occupation of Respondents, and % in agreement:
Public; Teachers; Farmers; Scientists;
New inventions 92.5 88.1 93.9 95.3
Information 84.6 71.8 82.2 80.6
New plant varieties 70.8 49.1 82.7 65.9
New animal breeds 59.1 50.9 68.5 62.8
Genetic material 51.2 33.9 64.5 53.1
The Ethics of Patenting Animals
We should examine the ethical arguments that are commonly expressed when talking about patenting of animals. The ideas have been discussed throughout this section, it is useful to list the key points.
The major arguments for patenting animals include (OTA 1989);
* Patent law regulates inventiveness, not commercial uses of inventions
* Patenting promises useful consequences (e.g. new products/research)
* Other countries support patents, so our country needs to if the biotechnology industry is to compete
* If patenting is not permitted, useful information will become trade secrets
* Patenting rewards innovation
The arguments against animal patenting include;
* Metaphysical concerns about promoting a materialistic conception of life
* Patenting will lead to increased animal suffering
* Patenting promotes inappropriate human control over animal life
* Some countries do not permit animal patents
* Patenting promotes environmentally unsound policies
* Patenting produces excessive burdens on agriculture (increased costs to consumers, payment of royalties for succeeding generations)
Most of these issues will not be affected by permitting patents, as the issues are similar to those existing prior to the patenting debate (e.g. animal rights, adverse effects of high technology on agriculture, the distribution of wealth, international competitiveness). This issue remains contentious and the fact that different countries have conflicting policy reflects this. The issue is closely related to the commercialisation of genetic engineering, but some sort of breeding protection is already accepted for farming, we need to ensure that farmers can continue to use new animal varieties and that the research that produces them is paid for so that there is an incentive to develop new varieties of benefit to society.
Patenting of Genetic Material
As stated to qualify for a patent an invention must be novel, non-obvious and useful. If the claimed invention is the next, most logical step which is clear to workers in that field, than it cannot be inventive in the patent sense. If a protein sequence is known, than the DNA sequences that code for it will not in general be patentable, unless there is a sequence which is particularly advantageous, and there is no obvious reason to have selected this sequence from the other sequences that code for the protein (Carey & Crawley 1990). The invention must also be industrially useful. In the case of natural products there are often difficulties because many groups may have published progressive details of a molecule or sequence, so it may have lost its novelty and nonobviousness.
There are some patents on compounds that have a relationship to genetic material, such as chemicals 5-fluorouracil which is related to ordinary nucleotides. It is an antiviral agent, and integrates in DNA, but is essentially the same as an ordinary drug. There are patents on short oligonucleotide probes used in genetic screening. These are essentially short pieces of the human genome. There are also patents on protein molecules which have medical uses, such as erythropoietin. In this case the protein structure is patentable if it, or the useful activity, was novel when the patent was applied for. If someone can demonstrate a use for a larger piece of DNA than they can theoretically obtain a patent on it. An example of a larger patentable section of genetic material would be a series of genetic markers spread at convenient locations along a chromosome (Saltus 1986). If the molecules are new, non-obvious, and can be chemically defined and their use described, then they are individually or collectively patentable. Another set of genetic markers can be found on the same chromosome and separately patented if they also meet those criteria.
There are different areas for which a patent may be obtainable. The direct use of products, such as therapeutic proteins, is well established. The information may be used in the study of a particular disease. An example of this is the introduction of a gene into an animal to make the animal a model of a particular human disease, and it was for this reason "Oncomouse" was patented. A third field is the use of genetic information to cure a disease, for example using the technique of gene therapy with a specific gene vector. However, with the completion of the genome sequence of many organisms, including humans, any new genetic material will no longer be novel as it will be available in a database (Carey & Crawley 1990). If researchers decided to apply for patents on every new protein sequence, they may also fail because of the lack of fulfilling the usefulness criteria. It is therefore likely that in the near future patents will be difficult to obtain on gene products, though it is expected that prior to the sequence determination there will be many applications for these different types of patent.
There are major questions which remain unclear, such as the scope of patents. Whether altering a few amino acids in a protein to improve the efficiency is patentable and the limits of this. Such changes may be obvious to anyone with knowledge of enzymology and may fail under that aspect of patent requirement. The issues of infringement of existing patents is also difficult, as new methods to effect similar genetic changes are developed (Adler 1989). The interaction between the system of plant variety rights, and the newly emerging area of animal variety rights, is important. Patent laws are very important as they influence the pace of developments in biotechnology, and are a fundamental part of the driving force behind the new technology. However, such decisions are also political,and will remain so (Smith 1988).
Biotechnology is a global issue. It can be used in positive or negative ways. It is most likely that it will be similar to other technologies and serve the interests of the rich and powerful more than it serves the needs of the poor. As it becomes commercially tied to companies which enforce patents or protection rights it is not likely to aid the third world so much as it would if equal access was given and may be inconsistent with human welfare. There is much potential, such as for universal vaccination programs and improved crops, but the companies will be trying to make a profit - that is their function. The solution probably involves the use of United Nations agencies that could provide a fairer distribution of benefits. New crops do have associated problems, they may aggravate genetic erosion, and accentuate inequalities in the farming population. Farmers will become more dependent on transnational agrobusinesses (Bogeve 1987, Fowler et al. 1988).
The potential impacts of advances in biotechnology will not only be irreversible, but they will introduce major and unpredictable changes in the global organisation and distribution of production. Countries which rely on the export of high value commodities are likely to be affected by these advances. Since the growth of agricultural complexity in the sixteenth and seventeenth centuries there have been plant and seed collectors who have taken useful plants to Europe and North America. In fact, plants were collected and planted for their products by Queen Hatsheput of Egypt in 1495 BC, and there are worldwide examples of such movements. The appearance of botanic gardens in Europe in the sixteenth century aided this process. An interesting example is that from a single coffee tree in the Amsterdam gardens came the seeds to plant most of the coffee in South America (Juma 1989). The movement of plants is closely associated with major European empires as a basis for more economic expansion. Thomas Jefferson said "the greatest service which can be rendered to any country is to add a useful plant to its culture". This idea is still being pursued, which has and will continue to have, a powerful effect on third world countries. The raw resources of the new biotechnology industry are genes, which are often introduced from third world countries with no renumeration. The gene banks and germ plasm stores are mostly under the control of developed countries.
There are a few examples of technology transfer to the third world. One interesting example which was cited by Gibbons (1990) is the use of potato tissue culture in a remote Vietnamese village, in people's homes. Important routes of technology transfer include the sending of students and scientists from the third world to do research in laboratories in the developed world. One cited reason for a failure to transfer to the third world from biotechnology companies is that many third world countries are under no obligation to follow the patents issued elsewhere, so companies results can get stolen if they were to transfer them there, hence they do not. There will always be a conflict between financial interests and human welfare, one of them has to be compromised. A danger with the long regulatory delays in developed countries, is the people in the third world may directly try GMOs if they are seen to be needed.
The medical advances using new genetic techniques do have implications for the third world. More than other types of medical research in new technology, genetic engineering should contribute to health. While genetic screening services are in the distance in developing countries, they will come, when cheap screening methods have been developed. For example the use of the polymerase chain reaction (PCR) to amplify DNA means that radioactive DNA probes do not need to be used (radioactive isotopes may not be available, as well they decay), rather colourimetric enzyme assays can be linked to the tests. This offers much promise. The research in tropical diseases will be aided. The development of safe vaccines will also be of great benefit.
The genetic information, especially of the human being, belongs to all humanity. The benefits that come from its discovery and use should show us how all humanity is one. We will see how the genetic constitution of all humans from different races is the same. We will see how all of us have mutations, no one is perfect in their genetic structure, or should I say perfectly normal. Decisions on the use of genetic manipulation in one country will affect other countries, because people move, change their countries. It is therefore imperative that the decisions about any future germline genetic manipulation, especially of humans, take into account people's opinions worldwide. This may be best handled by an international forum, which national committees should interact with.
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