Biotechnology and gene technology

• Genetically modified organisms (GMOs)
• Transgenic animals and insects
• DNA vaccines
• Human biotechnology
• Diagnostics
• Gene therapy
• Stem cell research
• Debate and institutions
• Patents
• Commercialisation and empirical research

Genetically modified organisms (GMOs)

Gene technology today is an important part of modern biotechnology and is used, among other things, to give bacteria, plants and animals new properties. This is possible by inserting a gene from, for example, a bacterium, into a plant or animal (transgenes). In some cases, genes from closely related or the same species are also transferred (cisgenes). The producers develop GMOs for the purpose of giving us vaccines and medicines, more effective aquaculture and agriculture, and cheaper food.

Insect-resistant and pesticide-tolerant plants or plants with a combination of these properties are the most common GM plants. Soon the market will offer GM plants that tolerate drought, are more suitable for producing ethanol, medicines and vaccines and industrial products (for example the Amflora potato, which has an altered starch content), and plants with an altered fatty acid composition.

Norway has adopted restrictive regulations concerning the use of GM plants in agriculture. In the period 2007–2014, feed producers in the aquaculture industry had authorisation to use processed GM plants in the manufacture of fish feed. The licence was valid for one year at a time and only allowed producers to use GM plants for feed production in emergencies (i.e. if it became difficult to procure non-GM feed ingredients). Since the producers did not use GM plants during this period, the licence was withdrawn in 2014. By the same token, in 2015, the Norwegian authorities recommended approval under the Gene Technology Act of GM maize for import and processing. Before this maize can be used for food and feed it has to be approved under the Norwegian Food Act.

The producers of GM plants promise higher quality and greater efficiency in agriculture, while the sceptics are concerned about unforeseen effects on health, the environment and society. The expected consequences are short-term benefits, while the unintended consequences (for health and the environment) are often poorly investigated and may emerge over time.

GM plants form part of a complex ecological system. Animals that graze on GM plants or other animals higher up in the food chain, may suffer unintended effects. The possibility of dissemination of genes from a GM plant via pollen or seeds to adjacent farms is also important, bearing in mind our need to cultivate plants in a responsible manner. For organic cultivators with fields near GM cultivation fields, the possibility of pollen and seed from GM plants spreading to their own means that the farmer can no longer guarantee that the crop will be organic. It is still unclear who must compensate for any loss of income due to the spread of genes from GM plants. This issue is discussed today under the key word "coexistence". The development of resistance among target organisms is also considered an unintended effect. It has been reported that insect pests have developed resistance to the insect toxin in insect-resistant plants, while in fields of herbicide-tolerant plants, herbicide-tolerant weeds have begun to turn up. The development of resistance will lead to a need to use stronger insecticides and herbicides.

The greatest research challenges presented by GM plants are the need to identify good methods and establish model systems that can be used to study possible adverse effects on health and the environment. Possible consequences may be influenced by a number of climate and environmental parameters, so the research has to be carried out where the GM plants are to be cultivated. At the same time, research on the effects of GM plants raises a number of more fundamental questions such as: What research methods should we use for investigation of possible risk? Should this type of research be conducted by those developing the plants? Should we only consider potential harm today, or also harm that may develop in a longer time frame, such as 10 to 50 years from now? What standards should we use for assessing the risk presented by GM plants? Is the level of harm associated with traditional agriculture an acceptable standard, or do we want to make ecological agriculture the standard? Different standards could give us different answers. Who is to be responsible for conducting this research? Who is to pay the costs (producers, general public, authorities) of any undesirable health and environmental effects? On the other hand, if scepticism implies not wanting to use a GM plant, who is responsible for the ensuing lost environmental gain or economic growth if the GM plant proves to be safe? This raises research ethics questions relating to risk and uncertainty. Different types of uncertainty have led to increased emphasis on exploring different types of uncertainty, and to discussions on how to handle the identified uncertainties. In the event of uncertainty, the precautionary principle is often cited. However, there is disagreement with regard to how this principle should be applied and whether it has any implications for how the research should be carried out. (See also Risk and uncertainty, Uncertainty, risk and the precautionary principle in Research ethics guidelines for natural science and technology, and Risk and Uncertainty - As a Research Ethics Challenge)

Apart from the risk aspect, there are other ethical aspects that are relevant in relation to GMO. The Norwegian Gene Technology Act is unique in that it has five criteria (environment, health, societal benefit, sustainability and ethics) for approval of a GMO. Work has been conducted in Norway to elucidate what should form the basis for an evaluation of sustainability. In the EU and countries that have ratified the Cartagena Protocol, there is a growing focus on socioeconomic effects. Little is known today about GMOs and their relations with socioeconomics, societal benefit and sustainability. It is therefore highly relevant for this research to be initiated, and there is a need for more transparency on the part of those who are developing and selling GMOs in terms of experience associated with cultivation in countries that have approved GMOs.

Transgenic animals and insects

Animals that have had new genes introduced by means of gene technology are called transgenic. This type of technology is used in five areas:

1. Gene technology is used in agriculture and aquaculture to modify characteristics such as growth rate, resistance to the cold and to disease, and nutritional content. Internationally there has been most focus on transgenic, fast-growing fish.
2. In the medical industry, gene technology is used to produce medicines and organs. An animal can for example be induced to produce hormones or proteins (recovered from the animal's milk or urine, also called "zoopharming"), which can be used to treat various illnesses. As of today, one product has been approved, ATryn. It is obtained from goats, and is used to treat humans with an anti-thrombin deficiency.
3. In order to address the shortage of organs, there has been research into possibilities for xenotransplantation, i.e. transplantation of organs from transgenic animals to humans. To enable the human body to accept these transplanted organs, the genetic composition of the animal organ is altered by insertion of human genes.
4. Gene technology is a tool in the study of diseases, where transgenic experimental animals are developed for use as models in order to understand the development of a disease and to improve treatment. Transgenic mice, in particular, have been used to study the development of cancer (oncomice).
5. In order to combat serious insect-borne diseases and pests, gene technology is used today to alter genes related to the development of disease in and/or the fertility of pests.
6. An important ethical issue relating to the use of gene technology to alter an animal's genes is whether the animal suffers, and whether a possible worsening of its welfare can be justified. It has been reported that transgenic salmon (those with the fastest growth rate) have deformities of the head, jaw and gills, and that their body shape has changed. These are defects that have a bearing on their food uptake, gill function and ability to swim.

The possibilities of producing medicine with the aid of transgenic animals probably have little effect on the animals' welfare, but animals that are modified so that they can be used to study the development of human and animal diseases may experience pain and suffering. A fundamental ethical question associated with the use of experimental animals generally is whether it is acceptable to conduct research that entails an animal losing its intrinsic value, when it is used as a means to other ends. Other relevant questions are whether there is sufficient similarity between humans and experimental animals for the research to yield transferable results. The question therefore arises of whether it is acceptable to use experimental animals when the resources could have been used on alternative research. (See also Animals in research).

Xenotransplantation raises a number of ethical questions regarding people's acceptance this as appropriate treatment. Would it feel unnatural to have an animal organ transplant? Could infectious viruses be transferred from animals to humans? What restrictions on private life should be introduced to prevent any infection transferred from pig to patient through xenografts from spreading further? Is it right to modify higher animals in order to meet our own needs? Is it wrong to create a hybrid between human and pig? What requirements should be made with regard to the scope and content of informed consent in connection with xenotransplantation (particularly since it cannot be possible to withdraw from infection monitoring?) The requirement of informed consent, which is fundamental with respect to medical interventions in people's bodies and private life, is an important guarantee of due process for the individual. What type of information must be given about a particular technological application in order for consent to be regarded as "informed"?

The use of gene technology to modify pests represents a new possibility in biological control. This strategy is also called GM biocontrol. The organisms in question are developed to be able to spread and reproduce so that they can be used to gain control of invasive species that, in new environments, have become pests (like possums in New Zealand and rabbits in Australia), and to reduce the transmission of disease from insect species that transmit disease-bearing microbes and viruses to humans (for example mosquitoes that transmit malaria and dengue fever). Since these GM biocontrol organisms are developed to be able to spread, they also represent a risk. They will have a far greater capacity to spread than the GMOs we use in agriculture. This presents challenges as to how we should conduct research on unforeseen effects on wild species and on the ecosystem.

Another important topic is the relationship between benefit and risk. We have a strong need for biological control of pests and invasive species, but how do we weigh the potential benefits (less malaria etc.) against the uncertainty associated with unforeseen environmental effects? The implications for ecosystem services and the function of the various species in the system are also relevant in this connection. Since GM biocontrol organisms can disseminate across national boundaries, they also present challenges in connection with legislation and procedures for approval, surveillance, information and responsibility.

DNA vaccines

DNA vaccination is defined as intentional transfer of genetic material (DNA or RNA) to somatic cells in order to influence the immune system. In recent years, DNA vaccines have received a great deal of attention, especially since they represent a novel possibility for preventing diseases against which there are no reliable vaccines at present. There are many uncertainty factors with regard to what consequences DNA vaccination may have for the organism that is vaccinated, and whether other organisms in the surrounding environment will be affected. It is also unclear at present how DNA vaccines should be defined and regulated, and whether the vaccinated organism can be defined as GMO, which may have implications for market acceptance. If DNA-vaccinated salmon is labelled as a GMO, will this affect exports to other countries? Is it conceivable that amending the legislation will result in greater acceptance for the use of DNA vaccines? And may such amendment influence the use of other DNA treatments, such as gene therapy?

Human biotechnology

In connection with humans, modern biotechnology includes methods for producing medicines, for detecting a genetic disposition or a disease or disorder, methods for curing diseases, and methods for enhancing human characteristics.

Diagnostics

With the aid of modern biotechnology, new diagnostic and therapeutic options have increasingly become an integral part of the general range of health services. Genetic tests include:

1. Preimplantation diagnosis (PGD) on fertilised eggs to detect diseases.
2. Prenatal diagnostic testing conducted on foetuses in order to detect/exclude the possibility of deformities or diseases such as cystic fibrosis, Folling's Disease etc.
3. Diagnostic tests conducted on a person in order to detect hereditary diseases, either presymptomatically, meaning the detection of a disease that will not turn up until later in life (like Huntington's chorea), or predictive, where a person's disposition for a hereditary or semi-hereditary disease (such as breast cancer) is identified. Predictive tests do not provide a definite answer as to whether a person will become ill.
4. Genome sequencing. A person's entire genome can be sequenced, and unlike points 1–3, which only concern certain genes, genome sequencing can provide information about all genes. How this can be used in the diagnosis and treatment of disease is not clear.

PGD and prenatal diagnosis, in particular, have raised major ethical questions, since they entail preventing disease and disabilities. Whereas some maintain that PDG is preferable to later selective abortion after amniotic fluid tests, others believe that the decision is taken away from the woman herself, and makes the choice a purely medical question.

Another matter is the question of which values should be made the foundation for and be expressed through the tests that are offered. For example, one concern is that unlimited choices may lead to respect for the integrity and diversity of the individual being put at risk. Others point out that diagnostics can lead to a reductionist view of humanity, where a worthy life for a human is equated only with the absence of disease or disability. This in turn can affect the frameworks for the support offered to children and parents with serious diseases. Since the development of good tests entails research on unfertilised eggs, the question also arises of whether this type of research may influence perception of the value of the unborn life.

The purpose of genetic tests is to detect disease at an early stage. The focus of diagnostics has thus changed, from detecting disease to detecting the risk of disease, which opens the way for the possibility of preventing future diseases, for example through close monitoring and changes in lifestyle. Access to genetic information creates opportunities, but also a responsibility to relate actively to the genetic aspects of one's own existence, and may have consequences for the individual's future and family relations. This has led to concern that knowledge of a possible illness may lead to unnecessary invalidisation, and change our perception and definition of the concepts of illness and wellness. How does one live with the knowledge early in one's life that one has a high risk of Alzheimer's Disease? How will knowledge of genetic disposition for disease or disorders affect our perception of ourselves and our behaviour in relation to sick and disabled people? Might this possibility of predicting future risk of illness lead to increased pressure to introduce new mass screening? Will this lead to an increased supply of self-tests, marketed, for example, through the Internet, without any offer of guidance in genetics and subsequent follow-up? Medical tourism is a growth industry today where medical centres offer a variety of services such as experimental treatment (stem cells and gene therapy), genetic testing, egg donation and surrogacy. This is possible because of different medical legislation in different countries, but alongside the research ethics issues, it also raises problems related to follow-up in the home country in the event of medical complications, and also presents legal challenges.

Increased understanding of hereditary diseases opens the way for new value-based choices. How should society's resources be distributed between research and other needs? And what considerations should govern the distribution of resources? Will the research and its applications benefit those who need it most, or will it help to exacerbate social inequalities? Research and technology development is market-oriented, and therefore automatically targets markets and groups with strong purchasing power and those who have the ability to influence the spending of public resources. Needs that are not in demand by strong pressure groups or do not have a high market value may accordingly be neglected. Which alternative systems and mechanisms can help to balance these discrepancies? Should it be lawful to use products and services from other countries that are based on research that is not permitted in Norway?

Another issue raised by this research is the implicit perception of the manipulability of processes that were previously regarded as natural, such as aging. Whereas senile dementia and a certain frailty of the body have been perceived up to now as natural consequences of growing old, the new knowledge of our genetic make-up means that these processes can be regarded in the same way as other hereditary diseases. Expectations of possible treatment accordingly arise. Thus research has begun to question what was previously regarded as a natural lifespan.
This increased access to information also raises new questions relating to consent, management of personal information and prevention of abuse. Can insurance companies require clients to divulge the results of genetic tests and genome sequencing? Should the police be able to use genetic knowledge to solve crimes? Should it be possible for employers to use the knowledge, and can this knowledge be used to prioritise use of resources in the health services?

Gene therapy

Gene therapy makes it possible to alter one or more genes that cause illnesses that cannot otherwise be treated. A distinction is made between gene therapy on somatic cells (all the cells in a body apart from gametes (sex cells)) and on gametes. In gene therapy on somatic cells, the procedure on humans aims to repair the gene that causes disease. Gene therapy on gametes (ova (egg cells), sperm)) or fertilised ova is most controversial, as the intervention will be passed on to future generations. Recently developed technology such as CRISP/Cas can also alter genes, and should therefore also be covered by the term 'gene therapy'.

Gene therapy and PGD make it possible to prevent and treat on the one hand and to 'design' on the other. For example, PGD can be used to select gender. The same applies to the possibility of deselecting disabilities and diseases. Tissue typing, for picking characteristics intended to ensure that tissue or organs from a future child can cure its brother or sister of a serious illness, is another example. These examples show that it is possible to design children with particular biological characteristics that, to a greater or lesser extent, are intended to realise particular social purposes. Where is the distinction between therapy, improvement and prevention? Where do we draw the line? These are questions that challenge our view of nature and normality, and require ethical, legal and empirical evaluations related to the perception of identity and possible instrumentalisation of human beings. Can we regulate research so that we find satisfactory solutions to these problems?

Another dilemma is that the potential latent in gene therapy can lead to expectations and promises being linked directly to questions of access to grants, and give rise to uncritical and unrealistic hope dynamics, with underestimation of time-consuming innovation processes. This may overshadow the need for quality assurance, for prudent regulation and for development to take place in accordance with important social needs and accepted ethical norms. In a future where we may have the opportunity to cure serious diseases, it is easy to forget that gene therapy also entails a risk of unexpected effects. For example, there have been reports of gene therapy having unexpected effects such as early death and the development of rare diseases.

Stem cell research

Today research takes place on stem cells from adults, children, umbilical cords and cloned embryos. The most promising area, but also the most controversial, is curing diseases like Alzheimer's and Parkinson's with the aid of stem cells from cloned embryos. With stem cells from cloned embryos, the patient gets fresh cells, tissue or organs from his or her newly produced twin. For many, the ethical problem associated with therapeutic cloning appears to be the cloning itself, while for others it is the fact that in carrying out therapeutic cloning we are also accepting the production of human life exclusively for research purposes. The question of whether embryos are covered by protection in their capacity as human beings with moral worth is a difficult one. Do we have an absolute obligation to treat them as goals in themselves, as we do with adult individuals? (See also Embryo, stem cell and foetus.)

Research ethics in the field of medicine has concentrated on protecting the individual and preventing immoral actions from being performed in the name of research (see the Declaration of Helsinki). In Norway, therapeutic cloning is prohibited, and this has given rise to an interesting debate around the questions: Should we refrain from using the potential opportunities in therapeutic cloning and research on fertilised eggs? Should we be able to use the published research results from countries where such research is legal? For example, if treatment of Parkinson's disease becomes possible in Denmark, it will hardly be possible to prevent Norwegian patients from going there for treatment. Have we then turned ourselves into a sort of ethically dubious free riders?

Debate and institutions

In recent years, great emphasis has been placed on promoting a wide-ranging public debate on the use of new technology. New forums have emerged (like consensus conferences, workshops and questionnaire surveys. See also Research and society) for discussion, dialogue and consultation. Public attention has provided more insight into and knowledge of ethical and social aspects, and has influenced confidence in society's ability to regulate and control developments in modern biotechnology and gene technology.

A weakness of the present system is that institutions that are required on behalf of society to monitor, prevent risk and limit environmental, human and societal costs, are not involved until the technologies have largely acquired their form and applications. (See also Research and society.) As a result, the debates have emerged "downstream" of the innovation processes, and the ethical and social issues have accordingly been disconnected from the broad economic and political issues relating to joint societal goals, control, power and responsibility. In this phase, opportunities for negotiation may be limited, partly because of the large, locked-in investments in technological projects that are at stake.

We must increase our ability to identify and formulate more fundamental issues associated with societal development, to enable us to bring such questions and considerations as early as possible into the processes and institutional systems where technological development is shaped, controlled and regulated. This is important, because it is in the early, formative phase of developments ("upstream") that objectives are formulated, tasks assigned priority and resources mobilised under the sponsorship of the research and innovation actors. A challenging question in this connection is how public-oriented technological assessment can be brought into such processes at an earlier stage, and how good and responsible research can be organised and conducted with a view to securing greater influence on the design of technologies and choice of applications. (See also Methods and method development for ethical evaluation).

Patents

There is political disagreement in Norway surrounding patenting and intangible rights associated with modern biotechnology and gene technology where patenting of naturally occurring cell lines, microorganisms, plants and animals is desired. This was especially evident in the Bondevik government's divided opinion during the debate on the EU's controversial Patent Directive in 2003. Commercial exploitation of genes is particularly relevant with respect to exploitation to improve the quality, increase the growth or increase the resistance to diseases of production animals and food plants, for the production of medicinal and industrial products and the development of experimental animals for medical research.

Patents are regarded as a good thing because they promote innovation and the development of new products and processes. On the other hand, patents may entail problems for further research by preventing the free flow of information, and may delay the development of new products and tools that can be used in diagnostics. Commercialisation of university research may lead to a reduction in access to general scientific and technological knowledge. Some of the criticism regarding patents is also value-based ("Life cannot be patented") and often raises the question of who is the rightful owner. This latter issue is of particular relevance to bioprospecting. Bioprospecting involves conducting systematic surveys for valuable genetic and biochemical resources from plants used in traditional medicine, and from biodiversity in general. When the purpose of bioprospecting is commercial exploitation of biological material, it has been negatively termed biopiracy and gene robbery, because pharmaceutical companies have patented and exploited genetic material from natural resources without returning any benefits to the site of origin of the material. The counter-argument from the other side is that when this has taken place in poor countries, the valuable resources would not have become available to people in other countries without the assistance of pharmaceutical companies. This is a subject that requires more investigation and is also of great relevance to Norway since we are now going in for marine bioprospecting, where ownership rights and rights of use of resources will be an important topic.

Commercialisation and empirical research

In recent years, modern biotechnological research has been under strong pressure to promote the commercialisation of scientific results in the form of patents, licences and the establishment of spinoff enterprises. There has also been a desire to create closer collaboration between academia and industry. This has led to integration of the interests and motives of non-scientific, commercial and resource economics agents into the organisation of research and into its norms and incentives system. Some see this development as a matter for concern that can weaken the independence of science and traditional norms of pursuing truth as an end in itself. Are the traditional goals and norms of empirical research subject to particular pressure in biotechnological research? Is it important to uphold these norms in order to realise the technological and commercial potential of research?

Transparency is a goal of research, but given a greater degree of commissioned research and external funding of research projects, this principle may be undermined. Confidentiality means that information is restricted to those authorised to have access to it. This means that other research institutions have difficulty in testing information regarding the safety of a product. Whereas private actors refer to protection of business secrets, the authorities refer to rules and regulations, regional committees for medical research ethics refer to confidential case management, and researchers are bound by secrecy through protocols or prevented from accessing documentation. There is a great need for more transparency, as it is in the interests of society in general to acquire knowledge of the efficacy of medicinal products and treatments, and at the same time knowledge about potential side effects. The same applies to studies of how safe GM food products are for health and the environment.

It is also unclear whether there is a connection between increasing economic and social pressures and the increasing examples of scientific dishonesty in recent years. Are researchers in modern biotechnology subject to a particularly strong pressure to achieve fast and sensational results, with increased risk of undermining the ethical standards of research, and thereby creating fertile ground for cheating and dishonesty?

This article has been translated from Norwegian by Jennifer Follestad, Akasie språktjenester AS.