Genetic engineering continues to provide great promise for drug discovery, assessment and production, but faces a strong battle on its public image. The term Genetic Engineering often induces public fear with regard to ‘GM crops’ and ‘designer babies’ therefore there is a need to manage public perception of this technology, especially as DNA editing technologies continue to advance science fiction into science fact, as Hannah Murfet examines below.
Back to Base-ics
Genetic engineering, put simply, is the adjustment of the instructions of our cells, the smallest functional unit of life. The genome is the sequence of information required to code for an organism, this consists of a long code of DNA represented by four letters (G, A, T and C) – the nucleotide bases. The sequence of these letters codes for the proteins and how often they are expressed.
New technologies such as CRISPR/Cas employ the use of RNA to guide enzymes to the target editing site. Like DNA, RNA consists of a series of nucleotide bases (with U instead of T), that guide the enzyme on where to cut the DNA, thereby facilitating editing the genome. Changes in the coding of the DNA or bases take a range of forms – from single letter changes, insertions, translocations and duplications. There are many genome editing systems from ZFN to rAAV, but the apparent efficiency of the CRISPR-Cas system is driving investigation into its medical potential and also raising questions on the technical ability to ‘Pick ‘n’ Mix’ designer genes.
Genetic engineering is routinely applied in medical treatment, particularly with the mass production of human insulin in bacteria since 1982. The future of this technology has continued with antibody therapy, where immune proteins are engineered and produced for targeted treatment of cancer and autoimmune disease.
Scientists are also able to make use of changes in coding to further our understanding of disease models such as cancer, where changes in the nucleotides can lead to changes in the way our cells behave. Cell and animal models can be used in pre-clinical trials to determine toxicity, and resistance patterns of new drugs and drug combinations. Work in these cell line models continues to develop, providing greater insights into pharmaceuticals before they reach clinical trials.
The future of genetic engineering takes this a stage further to target the cells in our bodies. Commonly known as gene therapy, this technology utilises a virus to insert a gene to treat disease where the coding is defective. In 2012, Glybera became the first gene therapy to be recommended for approval in Europe and last year went on sale in Germany for a record-breaking €1.1 million. The treatment works to restore the activity of a defective enzyme in the rare genetic condition, lipoprotein lipase deficiency. Gene therapy is one of the hottest areas in biotech at the moment, with a number of companies re-entering the field and growing investor interest, as highlighted at the recent JP Morgan Healthcare conference. The cost of these therapies is currently high, but the field of genetic engineering continues to evolve as new technologies are being adopted.
‘Pick ‘n’ Mix’ Designer Babies
While currently any modification to germ line DNA is illegal in the UK, new techniques such as the CRISPR/Cas system continue to bring ethical debates on designer babies to public attention. The apparent simplicity of the CRISPR/Cas potential to cut and insert bases seems on face value almost as simple as cut and paste on a computer, and while it is not as simple as that, there is certainly clear potential for non-clinical use. There is no doubt that the level of debate increases when comparing the clinical utility for genetically inherited diseases such as sickle cell anaemia versus ‘Pick ‘n’ Mix’ options such as eye colour.
While the commercial offer of ‘Pick ‘n’ Mix’ designer babies may seem a long way off, it is close enough for a need to review the regulatory and governance framework. As with any new medical practice, from pharmaceuticals to medical devices to practices such as IVF, measures of verification and validation are necessary to ensure the safety and effectiveness for patient use.
A Question of Ethics
The current work in genome engineering in somatic cells is creating some positive enhancements for medicine. With careful control and regulation the prospects for clinical treatment have massive potential, perhaps even one day early medical invention at the germ line stage. However it is vital to take care of the ethical implications of genetic alteration, in particular with regard to gene editing of human germ lines to ensure appropriate regulation of both clinical applications and crucially the ‘Pick ‘n’ Mix’ possibility. As this technology becomes more and more possible, it comes largely down to a question of ethics over the boundary between clinical utility versus human enhancement.
Any opinions expressed are the authors own