Understanding Biotechnology

What is Biotechnology

Overview of Biotechnology

History of Biotechnology

Why do we do biotechnology?

Biotechnology for the environment

Biotechnology for food and agriculture

Disease can occur when genes become defective through changes called mutations. These changes result in a new form of the gene – a new allele - which may cause it to function less effectively, or not at all.  In time, it may be possible to use gene therapy to replace an abnormal or faulty gene with a normal copy of the same gene.

Currently, gene therapy is an experimental procedure that aims to correct only defective genes that cause disease and not other characteristics. In the future, it may be used to treat ailments such as heart disease, inherited diseases or cancers.

None of us are perfect

Each human carries about half-a-dozen defective genes. Most of us do not suffer any harmful effects from our defective genes, because we carry two copies of nearly all genes. Scientists are looking at gene therapy as a treatment for genetic disorders. Absent or faulty genes can be replaced by working genes, so that the body can make the correct enzyme or protein and consequently eliminate the root cause of the disease.

How to do gene therapy

• Disabled viruses can transfer genes into a cell efficiently. However, it can be difficult to make a virus totally harmless, so some disease symptoms associated with the virus may also develop.

• Non-viral carriers include fat globules (liposomes) and artificial chromosomes (a sequence of DNA created in a laboratory). These can transport large amounts of DNA, but they are not as easily incorporated into the genetic material of the cell.

For background information on gene therapy, go to: http://www.ornl.gov/hgmis/medicine/genetherapy.html

The uses

• inherited disorders
  • severe combined immunodeficiency syndrome (SCID)
  • diabetes
  • thalassaemia
  • haemophilia
  • cystic fibrosis
• cancers of different types
• heart disease
• age-related diseases
  • arthritis
  • dementia

Mending a broken heart

Heart attacks cause damage to the muscle cells of the heart. Scar tissue forms , disrupting the heart's electrical system, and weakening the heart.

Recently, researchers have reprogrammed the scar tissue, making it behave like heart muscle cells.

The researchers, from the Children's Medical Research Institute (CMRI) in Sydney and the Children's Hospital Westmead, added two extra genes to the scar tissue cells. One gene programs the cell to be excitable, like a muscle cell, and the other allows the cells to communicate, passing on the electrical pulse of the heart.

Gene therapy trials

Ashanthi's cells were provided with genes encoding an infection-fighting enzyme that she lacked. Doctors removed white blood cells from her body, grew the cells in the lab, and inserted the missing gene into the cells using a viral vector. The genetically modified blood cells were then infused into her bloodstream.

This procedure is not a cure. The treated white blood cells only work for a few months, and the process must be continually repeated. Since that trial, more than 3000 people have received this treatment in human clinical trials.

Gene therapy is still an experimental procedure, and has suffered a number of major setbacks since this first trial. Some trial patients developed a leukaemia-like illness caused by the vector used to transfer the gene. Trials were temporarily halted to allow time for the development of safer gene transfer vectors, and are now underway again in several countries. Future techniques may be safer, and be able to deliver the correct gene, to the correct cells, in the correct tissues.

A 2007 gene therapy trial for inherited retinal disease had promising results. Patients had a modest increase in vision with no apparent side-effects.

The NHMRC is in the process of establishing an expert Cellular Therapies Advisory Committee to provide medical and technical advice to Human Research Ethics Committees on the clinical application of gene therapy. http://nhmrc.gov.au/about/committees/expert/ctac/index.htm

The challenges

It is important:

• to find the right gene
• to target the right cells in the body
• to deliver the DNA of the required gene into these cells
• to make sure the DNA is used correctly by these cells
• that the procedure is performed safely causing no injury or harmful side-effects.

To date, gene therapy has only been performed experimentally in human clinical trials, as there are several possible adverse consequences.

To see real benefit, future techniques will need to guarantee the safety of the technique and deliver the correct gene to the correct cells in the correct tissues.

Just your genes...?

The genetic change introduced by the therapy is not passed on to the patient's children. For the ‘new’ gene to be passed on to the patient's offspring, germline gene therapy has to occur - that is, a permanent transfer of the gene into the patient’s egg or sperm cells. This is illegal in Australia.

Currently, there is insufficient knowledge about the possible consequences for future generations of the use of these therapeutic techniques. A number of ethical considerations need to be taken into account before the therapy can be used widely.

These include weighing up the potential benefits for the patient against the harm that might be done to them or their children, and considering under what conditions it would be justifiable to make changes, so that they do not occur in future generations.

The genetics underlying most conditions is quite complex. Completely eradicating a particular form of a gene we believe to cause disease may have far-reaching consequences for future generations. That particular gene change may actually be advantageous in some circumstances.

For example, people who carry a copy of the allele that causes sickle cell anaemia have an increased resistance to the deadly infectious disease, malaria. If the sickle cell allele is removed from the population, many more people might die in areas affected by malaria.

Watch an animation from the Walter and Eliza Hall Institute of Medical Research that depicts aspects of the haemoglobin molecules and the mutant form that causes the disease sickle cell anaemia: http://www.wehi.edu.au/wehi-tv/dna/index.html and click on "Haemoglobin and
Sickle Cell Anaemia"

Gene therapies on humans are allowed under Australian legislation, but the National Health and Medical Research Council (NHMRC) sets strict guidelines for conducting trials and gene therapies on humans. These can be downloaded here:

Guidelines for Ethical Review of Research Proposals for Human Somatic Cell Gene Therapy and Related Therapies (1999) http://www.nhmrc.gov.au/publications/synopses/e38syn.htm

One possible future?

• hundreds of genes may be involved in any of these characteristics
• these genes interact with the environment in which we develop.

An example of concerns associated with gene therapy is ‘gene doping’ - the possibility of athletes abusing gene therapy to ‘genetically modify’ themselves to gain a competitive advantage.

Research is underway to use gene therapy to increase red blood cell production (and therefore oxygen delivery to cells) in people with severe anaemia – however, this therapy could potentially be used to boost the capacity of athletes.

Gene therapy which has so far been found to increase muscle size in animal models, and which is intended for patients with muscle wasting diseases, could in theory be adapted to strengthen particular muscles in athletes.

Read more:

ABC Health Report: http://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s1076995.htm

Scientific American: http://www.sciam.com/article.cfm?articleID=000E7ACE-5686-10CF-94EB83414B7F0000

Controversy exists as to whether ‘designer babies’ and gene doping will actually happen. Some people maintain that such genetic alterations are too complex and have too many serious ethical implications, while others claim it is ‘only a matter of time’.

A number of popular films have attempted to visualise a ‘genetically modified’ future. For example, the 1997 science fiction film, ‘GATTACA’, is about a futuristic society in which embryos are selected and modified for intelligence, physical perfection, resistance to disease and athletic ability. Children conceived in the normal way are treated as second-class citizens and relegated to menial jobs. While the film combines Hollywood action and adventure, it touches on a vision of a future that reflects many of the topical ethical issues and public concerns surrounding biotechnology today.