What is it and what is new?
Biotechnology is a descriptive term that covers a range of scientific tools which use living things to solve problems and make products. In the context of health and disability issues, this term covers many procedures that have existed for decades, including heart and kidney transplantation, blood transfusion, skin grafts, enzyme replacement therapy and bone marrow transplantation.
Recent developments in understanding the structure and function of DNA and genes, and the way in which cells grow and develop in the body, have led to a number of conceptual ideas about how new techniques in biotechnology may be applied to various diseases or disabilities.
Some of these newer techniques are described in this section. Our section on the medical uses of biotechnology gives some actual and some potential uses for the prevention and control of disease and disability. Read on for NZORD’s brief explanations of gene therapy, xeno-transplantation, cloning and stem cell technology, and genetic modification in medicine. To round out the whole picture, read our comments on The Human Genome Project which has acted as a catalyst to speed up the potential of these technologies.
Medical uses of biotechnology
Some of the things genome knowledge and modern biotechnology make technically possible for human health and disability:
- New tests to confirm a diagnosis of a disease or disability.
This means being able to accurately tell if the person has a particular condition or not.
- New tests to predict a disease or disability.
This means being able to tell if the person has a condition that will lead to the development of certain symptoms. The most well known form of predictive testing is newborn screening, and this is applied to all new babies for a limited range of conditions for which there is some treatment option.
- New tests for susceptibility to a disease or disability.
This means being able to tell if a person has the genetic makeup that means a particular condition is possible or even likely to develop, but in most cases, without any certainty that it will develop, or if it does, how mild or severe it will be.
- New test for carrier status for inherited conditions.
This means being able to tell if the parents or other relatives are carriers of the genetic characteristics that might lead to their children inheriting a particular disease or disability.
- New methods for prenatal testing of a foetus.
This means being able to tell if the foetus that is developing in a pregnant woman, is affected by a particular disease or disability.
- New technology and tests for pre-implantation genetic diagnosis.
This means using tests in conjunction with in-vitro fertilisation techniques, to determine if a fertilised embryo is affected by a particular disease or disability, prior to the implantation of an embryo into the woman so she will become pregnant.
- Enzyme replacement therapy.
This means producing an enzyme that is administered to the person as a medicine, and which takes over the function of a similar enzyme that the person's own cells are unable to produce in the right quantity, as a result of a genetic fault.
- Gene therapy.
This means using genes as medicine, for a person whose own genes have a fault in them. It involves introducing a new gene into the person to compensate for the incorrect expression of their own gene, and may also involve other action to stimulate an inactive gene, or restrict an overactive one.
- Stem cell therapy.
This means using stem cells, which are special cells that have properties that enable them to grow into a variety of different tissue types, and using them to replace or supplement particular tissue in a person with a genetic condition or health problem.
- Xeno-transplantation of cells from animals to humans.
This means taking tissue from other animal species and transplanting it into a person, to replace or supplement particular tissue that is affected by a genetic condition. This could also be used for other purposes such as heart valve replacements or skin grafts.
- Cloning of cells to assist with diagnosis or to improve the effectiveness of other treatments.
This means taking cells and using laboratory techniques to grow more of them to give a good sample to study for diagnosis. Cloning also includes combining part of one cell with part of another cell, to alter the characteristics of the cell that results from this combination.
- Targeted drug therapies.
This means using the precise knowledge of the function of a gene, and the protein or enzyme it produces, to produce a drug that is intended to act only on that particular enzyme or protein, and produce a correction to its absence, deficiency, or excess.
Gene therapy means introducing an active gene into the body's cells to compensate for the inactivity, or inadequate activity, of the person's own gene. Preparing replacement genes has been successfully managed, but devising an appropriate method of delivery into the appropriate cells of the body is a difficult technological task that has limited the application of gene therapy. As with all transplant procedures, immune reactions by the body are a significant issue to be managed for a successful outcome.
Trials of gene therapy have demonstrated the success of these techniques in a number of animal models of various disorders, and experimental trials have demonstrated success in human patients with Haemophilia A and Severe Combined Immuno-Deficiency.
Gene therapy has the potential to correct conditions that affect the brain and the central nervous system, and this has implications for a number of diseases such a Parkinson's disease and Alzheimer's, as well as for a number of conditions where the incorrect gene expression leads to intellectual disability.
Alternative methods of gene therapy are also under investigation. This includes trying to develop methods to activate inactive genes, or to correct overactive genes, without introducing foreign genes. This concept is known as gene repair, but is at experimental stages only.
A considerable amount of research is going on into ways of perfecting the technical issues so that gene therapy may be applied to a wider range of diseases and disabilities.
For further information visit the Human Genome Project site on gene therapy. This site contains more detail on how gene therapy works, what current research is being undertaken and has links to other useful resources.
Xeno-transplantation is the use of live cells, tissue or organs from non-human animal species, for transplantation into a human patient. Interest has grown in this area of biotechnology because up to 50% of people waiting to receive vital organ transplants, such as kidney, liver and heart, die while waiting for a donor organ.
Technical possibilities have increased as knowledge of immune reactions has grown. Increased technical capacity to combine genes from different species has also widened the options for this to occur.
In some parts of the world, including New Zealand, there have been experimental procedures undertaken to test the possibilities of xeno-transplantation. The New Zealand experiments were the transplant of cells from pigs to produce insulin in people with diabetes.
A 1997 report raised concern about possible disease transfer across species through the use of xeno-transplantation. As a result, limits have been put on the procedures, both in New Zealand and other countries, to ensure that more research into disease risks is carried out before further trials are undertaken.
In 2004 the same research team published a report suggesting the earlier concerns were misplaced. In 2005 the New Zealand Bioethics Council issued a discussion document on the Cultural, Spiritual and Ethical Aspects of Xeno-transplantation, and a significant public dialogue process took place. Details of this dialogue and references to the research on the topic can be found on the website of Toi te Taiao: the Bioethics Council [link no longer active]. In December 2005 The Bioethics Council recommended to the Government that xeno-transplantation decisions be made on a case-by-case basis.
Follow this link to the submission made by NZORD on the Bioethics Council consultation. A detailed submission from Diabetes New Zealand was endorsed by NZORD and is also posted on our site for information. Both called for approval to be given for further research and clinical trials of therapies derived from xeno-transplantation.
The Biotechnology Learning Hub provides an excellent resource that contains more details about xeno-transplantation, and the Science Media Centre discusses a recent case where a New Zealand-based biotechnology firm, Living Cell Technologies, is developing a treatment for Type 1 Diabetes derived from pigs.
Genetic modification in medicine
Genetic modification is the process of altering the properties of cells in an organism by changing the genetic makeup of the DNA in the nucleus of the cell. This can include deleting or changing genes, or transferring genes from one organism to another. When an organism has had these changes made to it, it will become a genetically modified organism.
Several techniques are used to make these changes. The one most relevant to medical applications is recombinant DNA technology. Special enzymes break the gene sequence out of the DNA strand and it is transported into plasmids which are small molecules in bacterial cells. Because the plasmids have the ability to move between cells and take their DNA with them, the wanted gene can then be transferred into other cells, usually bacterial cells, and the bacterial cells are now genetically modified.
The first use of genetically modified organisms in medicine was to use the bacteria as factories for the introduced genes. By fermentation techniques the bacteria could be multiplied many times over and the multiplication of the introduced genes would also multiply the protein or hormone that the gene would normally produce. This is the technique that allowed the mass production of products like recombinant human insulin for treatment of diabetics.
Other medical uses of this technology have been to genetically modify animals so that they express certain enzymes or proteins in their milk. This has been done to obtain medicine for human use, from rabbits, cows and other animals. When this occurs the animal becomes a genetically modified organism, but the medicine that is obtained, while the product of a genetic modification process, is not itself a GMO. It is a recombinant product but retains the characteristics of the original enzyme or protein.
The next step in the chain of possible applications of GMO technology is where a particular gene is used as a medicine in a person who has a disease or disability. This is gene therapy. The introduced gene will express the enzyme or protein that is absent or deficient, and in this way the person will be treated. As a result of this application of gene therapy, the person will, technically, be a genetically modified organism, as the introduced gene will have altered their genetic properties, but only in relation to the disease or disability they have.
The Australian Commonwealth Scientific and Industrial Research Organisation (CSIRO) provides a clear and short summary on genetic modification including a useful diagram and useful links to further information.
Cloning and stem cell technology
This expression has two distinct meanings. One is the creation of a genetically identical animal by replacing the nucleus in the egg, with the nucleus from an adult animal that is to be copied. This is the process that produced Dolly the sheep, and made the new-born animal genetically identical to its parent. This process is used in animal breeding in agriculture, but it is specifically prohibited by all existing legislation relation to human reproduction, including New Zealand legislation.
The other use of cloning techniques is known as therapeutic cloning and does not involve the production of a foetus. By using the cloning technique of transferring the nucleus from the person to be treated, into an egg, embryonic stem cells will be produced and can be multiplied in culture for medical application. It is anticipated that the resulting cells, when used for treatment of the person, will have compatible genetic characteristics and immune reaction will be reduced.
Stem Cell Technology
Stem cells are those cells which have the ability to continuously divide and develop into various kinds of tissue. They can be obtained from early embryos, foetuses from pregnancy terminations, umbilical cord blood, and adult tissues.
As these cells have the ability to develop into neurones as well as other tissues, there is interest in how they may be developed as treatments for a range of conditions for which there is particular complexity about providing effective treatment. The conditions for which they may provide promising advances are those that involve cell death, and for which the body does not seem readily able to provide its own repair. Examples are neurological disorders like Alzheimer's, Stroke and Multiple Sclerosis, vital organ damage such as heart disease, and inherited conditions like cystic fibrosis.
The value of stem cells may also be enhanced by additional techniques, such as genetically modifying them to ensure they express particular proteins. Or they might be cloned with cells of the transplant patient, to reduce the likelihood of immune rejection.
Therapies using cloned or genetically modified stem cells as a source of new cell development are not currently available and research on this approach is at early stages. However hematopoietic stem cells are used in transplant treatments as an alternative to bone marrow cells, and have proved effective in this.
There are ethical issues with stem cell research right at the early stages of the development of the technology. These issues arise because the sources of stem cells include fertilised embryos that are surplus to invitro-fertilisation procedures.
Cloning – the Human Genome Project website contains an excellent resource page on cloning. This includes a detailed description of what cloning is, and has links to ethics issues and recent research.
Stem Cell Technology – The National Institutes of Health in the U.S. provides a useful resource, which contains detailed information about stem cells. This site is logically ordered and easy to navigate. Closer to home, the Australian Stem Cell Centre, an institute funded by the Australian Government, provides a series of fact sheets as downloadable pdf files that cover a range of topics including a history of stem cell research and a detailed handbook for people considering undergoing stem cell treatment.