Drug Treatments and Genetic Modification
Some diseases, like depression and Parkinson’s disease, are thought to be caused by a lack of specific neurotransmitters in the brain. This means they can be treated using drugs which increase the concentration of neurotransmitters - some of these drugs will be manufactured using genetically-modified organisms.
Neurotransmitter deficiency diseases
Some diseases are known to be causes by a lack of particular neurotransmitters. Two examples of this kind of disease is Parkinson’s, which is caused by a lack of dopamine in the brain, and depression, which is caused by a lack of serotonin.
Parkinson’s disease is a movement disorder resulting from the destruction of neurones in regions of the brain which control movement. Neurones in this region of the brain produce dopamine, so neuronal death in this part of the brain results in a lack of dopamine. This means that when an action potential arrives at a neurone, the presynaptic neurone releases less dopamine into the synaptic cleft. Less dopamine receptors on the postsynaptic neurone are activated so less sodium ion channels in the postsynaptic membrane open. This makes it less likely for the threshold potential in the postsynaptic neurone to be reached, so a nerve impulse is less likely to fire. The reduction in neuronal transmission in parts of the brain associated in movement results in symptoms such as tremors and poor motor coordination. Parkinson’s disease is treated with drugs which increase levels of dopamine in the brain.
L-dopa is the main drug treatment for Parkinson’s disease. It has a similar structure to dopamine and is able to cross the blood-brain barrier and pass into the brain, where it is converted into dopamine by the enzyme dopa-decarboxylase. Dopamine cannot be given directly to patients since it cannot pass through the blood-brain barrier). L-dopa therefore increases dopamine levels in the brain, resulting in more nerve impulses along neurones in brain regions which are involved in movement.
Depression is a mood disorder which is thought to be caused, in part, by a lack of serotonin in the brain. Antidepressants have been developed to increase the levels of brain serotonin. A class of antidepressants known as selective serotonin reuptake inhibitors (SSRIs) work by binding to serotonin reuptake proteins within synapses, blocking the proteins and preventing them from reabsorbing serotonin.
Another substance which increases the brain’s serotonin levels is the party drug MDMA (ecstasy). MDMA prevents the neurone’s ability to reabsorb serotonin from synapses by binding to and blocking reuptake proteins on the presynaptic membrane. It also stimulates presynaptic neurones to release more serotonin. This increases serotonin levels in the brain and increases the frequency of nerve impulses along neurones in brain regions which are involved in mood.
Using genome sequencing to produce drugs
The Human Genome Project (HGP) was an ambitious target, set in 1990, to sequence all of the DNA found in humans. It took 13 years and has been used as an invaluable tool in medicine. Scientists are able to use the database to identify genes and proteins which are implicated in disease. This information can then be used to create new drugs to target those proteins. Genome sequencing has also identified tiny genetic variations between people where just one nucleotide differs - the fancy term for this is single nucleotide polymorphisms (SNPs). Some of these genetic variations are known to make some drugs less effective. This has resulted in a new area of healthcare called personalised medicine where doctors can prescribe a unique treatment plan depending on the genetic variations found in each individual patient.
However, there are social, moral and ethical issues for personalised medicine. There is the danger that a person’s genetic information may be passed onto third parties and used against them (e.g. if an insurance company knows that you have a mutation that is associated with breast cancer, or a SNP which means you may not respond well to a particular treatment, they may choose to charge more for a health insurance plan). There is also the concern that tailored medicine will increase research costs, making drugs more expensive and only affordable for more wealthy patients. In addition, more expensive drugs may be denied to certain patients on the grounds that they possess an SNP which indicates that they may not respond well to a treatment. Finally, if a patient knows that they have an SNP which means they may not respond well to treatment, it might have a negative psychological effect which means that the drugs responds worse than if they hadn’t been told about their genetic variation at all (kind of like a reserve-placebo effect).
Producing drugs using genetically modified organisms (GMOs)
Genetically modified organisms (GMOs) are organisms which have had their DNA changed so that they synthesise proteins which can be used as drugs. Restriction enzymes are used to cut DNA at specific sites to extract a gene of interest. The same restriction enzymes are used to cut plasmid DNA, creating complementary sticky ends. DNA ligase joins the two pieces of DNA together so that the gene of interest is now contained within a plasmid. This is called recombinant DNA. This is either placed in a virus, which will infect organisms with the recombinant DNA, or the plasmid will be taken up by bacteria. Plasmids and viruses which carry the DNA molecule are called vectors.
This process is used for the production of insulin.
The insulin gene is removed from human DNA using restriction enzymes.
A plasmid is also cut with restriction enzymes.
DNA ligase joins the complementary sticky ends to form the recombinant DNA.
The recombinant plasmid is taken up by bacteria.
The transgenic bacteria are grown in large fermenters to produce large amounts of insulin, which can then be extracted.
Bacteria aren’t the only organisms which can be genetically modified to produce drugs - plants and animals can be used too. For genetically modifying plants, a GM bacterium is first made using the process outlined above. The bacterium then acts as a vector, infecting a plant cell and inserting its DNA into the genome of the plant cell. The plant cell grows into an adult plant and all of its cells will contain the drug-producing gene. The plant cells will synthesise the protein which can either be extracted or the drug can be delivered to the patient by eating the plant. Cholera vaccines have been made using this method.
Genetically-modified animals are produced by injecting the gene for the protein (which will act as the drug) into the nucleus of a fertilised animal egg cell. This is then implanted into an adult animal and as the animal develops, every cell will contain the drug-producing gene. The protein produced from the gene is normally purified from the milk of the animal. This method has been used in goats to produce the drug antithrombin for treating people with defective blood clotting.
Issues with using GMOs in medicine and food production
GMOs are not just used for producing drugs, but also for improving agriculture. For example, genes can be added to crop plants to make them resistant to disease or more nutritious. However, the use of GMOs is controversial and there are some arguments for and against their use in medicine and agriculture:
Arguments for the use of GMOs:
Genetic modification can increase crop yield and make food more nutritious - this means that farmers can make more money and people will be healthier.
Genes for pest-resistance can be introduced into crops. This means that farmers save money on pesticides and the environmental problems associated with pesticide use are reduced.
Human proteins produced using GMOs do not result in allergic reactions - for example, insulin as a treatment for diabetes used to be extracted from the blood of pigs and cows. Nowadays human insulin is produced using GM bacteria which doesn’t produce an allergic reaction in patients and is more efficient.
Vaccines produced using genetically-modified plants do not need to be kept cold to stay effective - this is an advantage when vaccines are needed in remote regions where refrigeration is not possible.
Enzymes can be produced using GMOs and are often used in industrial processes e.g. in the manufacture of washing detergents and the textile industry. The use of GMOs makes these processes cheaper.
The process is cheap because once one genetically modified organism is made, lots more can be made through breeding the original GM organism. This makes drugs cheaper.
Arguments against the use of GMOs:
GMOs are often patented and the seeds are expensive to buy - this puts farmers in developing countries at a disadvantage.
If a GM plant cross-pollinated with another species, it could introduce the genes into other plants with unintended consequences. For example, cross-breeding a herbicide-resistant crop plant with wild plant species could create ‘superweeds’ which are resistant to herbicides. These could out-compete other plants with potential effects on the whole food chain.
There are ethical issues against the use of GMOs - should humans manipulate animals for our own benefit?
Religious reasons - do humans have the right to ‘play God’ and create new life?
Some people worry out the long-term impact of using GMO - there may be unforeseen consequences which are impossible to predict.
Did you know…
Scientists who have analysed shrimp in Suffolk, UK have found the presence of cocaine in every single one of them, with the presence of ketamine also widespread. The aquatic creatures are thought to absorb the drugs when the recreational drugs find their way into the water supply.
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