Personalised Medicine: The Pros and Cons

Since the Human Genome Project (HGP) was essentially completed in April 2003 there have been vast improvements in DNA sequencing technology, making whole-genome sequencing (WGS) both technically and economically feasible.

In October 2006, the X- prize foundation united with the J. Craig Venter Science Foundation to offer the ‘Archon X Prize’; a $10 million reward to the team that can build a machine capable of efficiently and effectively sequencing the human genome for less than $1000. Competition is high and companies are expected to reach this goal within a couple of years, making direct- to- consumer WGS affordable.

Is the large amount of information, generated by personal genome sequencing, entirely necessary?

Will WGS revolutionise modern health care?

One of the main areas that has had a high influx of investment by pharmaceutical companies is the development of ‘personalized medicines’. WGS can be used to predict a patient’s response to certain drugs or possible side effects. By identifying these pharmacogenomic variants, drugs and therapy can be tailored to the specific patient.

Another area of interest is the possibility of diagnosing a patient’s predisposition to disease, this previously would have only been possible by looking at family history. Geneticists will be able to reveal a person’s carrier status for autosomal recessive diseases and determine risk factors for certain adult- onset diseases. The ethical question is raised, whether to tell someone of a disease they will inevitably develop in later life? This may result in some life- style changes but could also result in unwanted psychological implications.

There are still many challenges to overcome before whole- genome sequencing is fully effective and useful in a clinical context. One difficult aspect is how to relay information to the patient; they must be adequately informed before they decide to be tested and must have appropriate counseling afterwards when they receive the results. For example, with the relative frequency of recessive autosomal diseases, patients must realize that there is a significant probability that they will possess at least one or multiple harmful recessive alleles. This information could influence a person’s reproductive decisions.

Awareness should also be brought to the underlying fact that there is uncertainty in the results, every mutation in a disease- causing gene only presents a ‘risk’ of developing the disease. Large areas of the genome still have unknown meaning; areas that could either exacerbate or counteract a certain disease- causing mutation.

Another continuing matter is the ever-expanding knowledge of genetic information. Although this may sound advantageous, it poses the problem that an assessment of an individual’s genome today may be redundant within the next year, as new discoveries and advances are made. Clinicians are then under the obligation to report this to the respective patients.

Building on this, is the issue of whether there is sufficient infrastructure in place to support the growing demand for WGS. Primarily, this lies in a shortage of specialist staff to interpret and convey results to patients. However, with increased computerization of the process and more efficient methods, this problem can be solved. Furthermore, to deliver a fully comprehensive report on an individual’s genome would require an accessible database with accurate information on all the known genetic diseases. This information is difficult to obtain and to keep up to date.

Drawing on the points highlighted, clearly there is a promising future in clinical WGS and the potential use of personalized medicines. Cost and capable machinery are now less of a limiting factor; we have transitioned into an era where ethics, legislation and the de-coding of genetic information are the greater obstacles. Once these associated issues have been resolved we will be able to reap the advantages and hopefully open a new door of modern healthcare.

Extremophile no.1

If you found yourself infected with Helicobacter pylori, you would be joining a club of 3.5 billion others, half the world population. You could be lucky and feel no symptoms. Alternatively, you may feel the full force of agonising stomach ulcers, vomiting, heartburn and bad breath.

Up until the mid 1980s it was common thought that gastritis (inflammation of the stomach lining) was caused by a culmination of lifestyle choices. These include the obvious alcohol and smoking, but eating spicy food was also thought to be a factor.

The scientific community furiously rejected the proposal that bacteria may be the cause of these painful stomach ulcers, as it was believed that no microbe would be able to withstand the powerful acidity of the stomach. It wasn’t until a dedicated scientist gulped down a broth containing a petri dish full of H. pylori that scientists believed the ‘unthinkable’.

The scientist’s name was Barry Marshall and he’d been working with Robin Warren to establish the cause of gastritis. Shortly after drinking the bacterial concoction, Marshall developed mild nausea and then began vomiting; a subsequent biopsy showed inflammation and also cultured the H. pylori bacteria, proving that it is the major factor involved in gastritis.

We now know that Helicobacter pylori is conclusively linked to gastritis, but how does the bacteria cause the ulcerations?

There is still much debate over the actual formation of stomach ulcers but the most widely accepted notion is that the H. pylori bacteria reside in the protective mucous layer, close to the epithelial stomach cells. They are helix- shaped and attach themselves to this epithelial layer using their flagella and chemicals known as adhesins, which bind to cell surface membrane lipids and carbohydrates. The presence of the bacteria disrupts the fine balance between acidity levels and the mucous layer. The corrosive gastric acid then attacks the underlying epithelial layer, causing the area to become ulcerated.

Large drug companies were not happy with this new discovery as it meant that cheap, over- the- counter antibiotics could more effectively replace their expensive ulcer- relieving drugs. As well as a course on antibiotics, people affected should take acid- reducing medication.

Marshall and Warren were awarded the Nobel Prize in 2005 for their valiant effort of discovering H. pylori and its link with gastritis. The scientific community was astounded by this new bacterium that could survive in such extremes, since then a whole host of thermophiles have been discovered.

But are there more out there? Not referring to thermophiles… cases where information is being withheld from the public to embezzle millions. Almost certainly.