How is GM technology applicable in the biomedical sciences?
Some of the most promising and powerful applications of GM technology are in the field of biomedical sciences. Since 1982, microorganisms have been genetically modified to produce pharmaceuticals for the treatment of human diseases. More recently, through what is known as “biopharming”, scientists have explored genetically modifying plants and animals so that these become living “factories” producing pharmaceuticals. Gene therapy trials have also been used with some success for the treatment of diseases such as severe combined immunodeficiency (SCID).
Can you provide some examples of drugs developed from GM technology?
The first genetically engineered drug is human insulin, produced under the trade name Humulin®. Approved by the United States Food and Drug Administration (USFDA) in 1982, Humulin® is produced by genetically engineering Escherichia coli bacteria to express DNA encoding human insulin. Before genetically engineered insulin became available, diabetic patients had to rely on insulin derived from the pancreases of animals such as cows and pigs. Patients can sometimes develop allergic reactions towards insulin derived from animal sources, especially if the preparations are of low purity. GM technology has thus provided diabetic patients with a source of low-cost, reliable, and high-quality insulin.
Numerous genetically engineered drugs have been subsequently developed and approved for use. The list includes, among others, human growth hormones, Orencia® for the treatment of rheumatoid arthritis, Remicade® for the treatment of Crohn’s disease and Herceptin® for the treatment of advanced breast cancer.
In 1986, the USFDA’s approval of a genetically engineered hepatitis B vaccine marked the start of the use of genetically engineered vaccines for humans. Most recently, in May 2012, the USFDA approved the use of a drug meant to treat a disorder known as Gaucher disease, Elelyso - produced using carrot cells.
Many more genetically engineered drugs are in the pipeline.
What is biopharming?
Biopharming (or pharming) refers to the use of GM technology to insert genes encoding useful pharmaceuticals into host animals or plants that would otherwise not express those genes. The host animals or plants then become living “factories”, from which useful pharmaceutical products can be harvested.
Proponents believe that biopharming offers an easily controllable, safe, and cost-effective method for manufacturing pharmaceuticals. While genetically engineered drugs are most commonly produced today using microorganisms in bioreactors, pharming requires less expensive infrastructure and production can be scaled up quickly in response to demands.
In 2006, the European Commission approved the first transgenic animal-derived drug – ATryn®. Derived from the milk of GM goats, ATryn® is a recombinant form of human antithrombin and can be used therapeutically as an anticoagulant.
The USFDA approved the use of another drug in 2012. This drug which treats Gaucher disease, is named Elelyso and is produced using carrot cells. Gaucher disease is an inherited metabolic disorder that leads to liver and bone problems.
Scientists and industry players are looking forward to GM plants in developing treatments for some of the most serious diseases such as cancer, HIV, Alzheimers, diabetes, and arthritis. Ongoing developments in this area include plant biopharmaceuticals which target hepatitis C, influenza and antibiotic-associated diarrhoea.
What is gene therapy?
DNA is the blueprint determining the characteristics of living organisms. Genes are specific segments of DNA and each gene encodes a product with a biological effect.
Sometimes, individual genes may become defective, leading to disease manifestations. Many diseases including cystic fibrosis, severe combined immunodeficiency (SCID), thalassemia, and sickle-cell anaemia are the result of just one malfunctioning gene.
Gene therapy has the potential to treat these genetic diseases. In a nut shell, it consists of the following steps:
The gene responsible for the disease is identified
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Functional copies of the gene are made available. In principle, cells from a healthy person can be removed and the specific gene isolated. Copies of this functional gene can then be made in the laboratory.
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Target cells bearing the “faulty” gene are removed from the patient.
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A carrier (also known as the vector) is used to insert a copy of the functional gene into the DNA of target cells. Currently, the most common type of vectors are viruses. These viral vectors are genetically engineered to replace their disease-causing genes with the therapeutic genes.
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The target cells now bear two copies of the gene – the original, faulty copy, as well as the newly introduced functional copy. These target cells are reintroduced into the patient’s body.
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The newly introduced gene functions on behalf of the original, faulty one, leading to alleviation of disease symptoms.
Gene therapy holds great promise for a variety of diseases. However, the technology is currently still experimental and no human gene therapy product has been approved for routine clinical use.
If gene therapy is so promising, then why has it not been approved for routine clinical use?
Before the marketing of any new drug or therapy, regulators and scientists have the responsibility to carefully weigh the risks and benefits involved. Although gene therapy holds great promises, the biology involved can be very complex.
Potential risks of gene therapy include:
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Concerns with viral vectors
In gene therapy, viruses are commonly used for carry functional genes into target cells. Although these viral vectors have been genetically engineered to remove their disease-causing properties, there is concern that they may revert back to their harmful nature once inside the patient’s body.
The viruses may also trigger the patient’s immune and inflammatory responses resulting in inflammation, toxicity and more severely, organ failure. In addition, as viruses can infect more than one population of cells, there is possibility of infection for other non-therapy-targeted cells in the process, causing other illness or diseases which can include cancer.
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Possibility of inducing tumours (insertional mutagenesis)
If the functional gene is inserted into a wrong place in a target cell’s DNA, it may disrupt the functions of other existing genes. Such disruptions may in turn lead to tumour formation.
Despite the initial hurdles and also failures in clinical trials some 20 years ago, gene therapeutics have seen much improvement in minimising its risks. Research carried out on cellular mechanisms especially in the immunological response of cells in various disease and cancer models has helped scientists understand the associated cellular mechanisms and how the immune system respond to virus-infected cells (in relation to cells undergoing gene therapy). As such, many risks leading from viral vector infection can potentially be minimised or even eradicated in some cases.
Recent developments in gene therapy have seen successes in the trials targeting diseases such as the hereditary haemophilia B, HIV and various cancer models.
The potential uses of GM technology in the biomedical sciences sound impressive. However, how safe are such applications?
The potential dangers of gene therapy have been answered.
All pharmaceuticals, whether GM-derived or not, are subjected to stringent scrutiny for efficacy and safety before they can be approved for marketing. Countless people have benefited since the first genetically engineered drug was approved in 1982.
Biopharming can present risks in the absence of appropriate measures. Gene flows (i.e. transfers of DNA from one population to another) and human errors can result in the contamination of conventional crops and accidental releases of pharm crops into the food supply. These undesirable effects can be minimized by using self-pollinating crops such as rice and flax to avoid gene flows, or non-food crops such as tobacco.
It is difficult to establish the absolute safety of any new technologies and GM technology is no exception. However, with proper regulatory safeguards, it is possible to derive benefits without compromising on safety.
In Singapore, which are the agencies involved in ensuring the safe use of biomedical-related GMOs?
In Singapore, pharmaceuticals, medicinal products, and clinical trials, whether GM-derived or not, are regulated by the Health Sciences Authority established under the Ministry of Health.
The agriculture sector is modest in land-scarce Singapore. It is therefore unlikely that any pharm crop will be cultivated on a large scale here. Nonetheless, should any party wish to carry out such agricultural activity, the Agri-Food & Veterinary Authority will ensure that the necessary safety measures are in place. The Singapore Guidelines on the Release on Agriculture-Related GMOs will apply and GMAC will provide advice accordingly.
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