It’s All in the Genes

Genetics and its successor genomics is currently one of the most hotly tipped scientific fields, with an enormous potential to revolutionize medicine and provide new therapeutic treatment for diseases. In the long term, patient’s susceptibility to certain diseases might be determined enabling possibly the prevention, or at least the delay of potentially fatal illnesses.

The study of genetics can be traced back to the 1860s when Moravian monk Gregor Mendel pioneered the study of inheritance founding the basis for what would later become modern genetics. Considered by many as the ‘father of genetics’ Mendel studied pea-plants and formed a number of observations about the traits that would be retained when certain pea-plants were crossed. Although pioneering in content, Mendel’s theories were not given the recognition they deserved until the 20th century. Since then, science has advanced tremendously with landmarks such as the coining of the term ‘gene’ and the chemical composition of DNA being found in 1909, the connection between DNA and the inheritance of traits in 1944 and the discovery of the structure of DNA in 1953.

Another defining moment in the science has been the completion of a rough draft of the human genome, which was completed by the Human Genome Project in early 2001. The purpose of which was to identify all the approximatel20,000-25,000 genes in human DNA, determine the sequences of the 3 billion chemical base pairs that make up human DNA. “The human genome project is the latest development,” explains Dr A Saggar, Consultant Geneticist and Physician, The London Clinic and St George’s Hospital. “It involved the discovery of the sequence of the genome. We have also identified what the genes are, although we still have no idea what they do. The challenge is to understand what the protein is and does.”

Developments in the field are ongoing, but one of the biggest breakthroughs is that genetics has morphed into genomics. “Instead of solving single-gene (so-called “Mendelian”) diseases which all occur early in life, i.e. childhood, people are now finding the genes behind common adult diseases,” says David Moskowitz, FACP Chairman, CEO and Chief Medical Officer GenoMed, Inc. “These are called “Polygenic” because they’re caused by many genes, but nobody know just how “Poly” they are. It now appears that cancers are caused by several thousand interacting genes, not just the 10 or 50 that people thought might be involved.”

A genomics revolution brings with is a wealth of benefits. The enlightenment that increased knowledge brings will spur medical discoveries and breakthroughs. “There is a huge amount of increased knowledge that has come out of the genomics revolution,” informs Brian Zambrowicz, Executive VP of Research, at Lexicon Genetics, a biopharmaceutical company focused on the discovery and development of breakthrough treatments for human disease. “It is comparable to trying to do chemistry before the periodic table, verses after. Once you know the elements, it is much easier to make chemical compounds. With genomics, once you have the code for all potential genes then you have a huge advantage.”

Providing patients with knowledge about their susceptibility to certain diseases will not only improve, but certainly save lives–catching ailments prematurely. “Genetics provides a road-map of diseases, which medicine has never had before,” enthuses Moskowitz. “We will be able to predict who will get which disease. The same road-map of genes will also tell us what drugs to use to prevent, or at least delay, the disease.”

Information overload is one of the disadvantages. “There is so much information that people do not yet know how to use it all wisely,” warns Zambrowicz. “So, scientists can end up with huge amounts of data but no solid leads on moving forward into drug development.”

Work in progress

In time, genomics-based drugs are likely to make a huge impact on the health industry. Already many company’s have been working on new drugs from genomics these include Amgen which has introduced one new drug from genomics, Kepivance, for treating oral sores caused by chemotherapy.

However, as bringing new drugs onto the market is not only time-consuming (around 12 years), but costly (US$1 billion) a reconsideration of existing drugs may be the best way forward. “People don’t necessarily want new drugs. They just want better outcomes,” claims Moskowitz. “It’s possible that existing drugs used at new doses may do the trick. Genomics makes it possible to re-purpose already existing drugs. This cuts the time down to a few years at the most. For example, my lab found in November, 1993 that overactivity of Angiotensin Converting Enzyme, or ACE, was behind kidney failure. By March of the following year, four months later, I was using a high-dose hydrophobic ACE inhibitor in my kidney failure patients and reversing their disease.”

Public enthusiasm for genetics appears strong with patients keen for further research into anything that might help them. In the second annual CGAT survey conducted by Cogent Research in Cambridge, Massachusetts in 2005 much of the US public is keen for their personal genetic information to be used to optimize their health. “Patients are eager for anything to help them,” explains Moskowitz. “Most patients I talk to think science may benefit their children or grandchildren, but not them. People are quite resigned to the slow pace of clinical medicine.”

Awareness of the science amongst the general public is quite high although there is still much confusion as to its benefits. Those individuals that take certain drugs will undoubtedly be in full support of further developments in genetics and genomics.
“There is no doubt that some people recognized they are benefiting form things learnt from the genome. For instance, people that take Gleevec because they have Chronic Myeloid Leukemia (CML) and women with HER2 positive breast cancer also understand the importance as they take Herceptin and it is very valuable for them. Over time this will expand as more people benefit from genomics or know someone closely that is benefiting from genomics and genetics based medicine.”

Despite support, there are reservations from some about progress in the field. A chief concern regards the implications of knowing your genetic profile in advance. Discovering that you are likely to contract a life threatening disease could have an enormous impact on a patient and their family, particularly if nothing can be done about it.

There are others who disagree with genetics and genomic due to moral or ethical reasons. Many fear what predicament we may one day find ourselves if scientist continue to meddle with our genes – possible enabling us to choose the genetic traits of our children. Designing babies might become only for those that have the means to afford it – leaving those that can’t with the dilemma that their children may lead their lives at a comparative disadvantage. Opposition from religious groups takes the stance that life should take its natural course without interference.

Despite this kind of operation, the use of genetics offers enormous potential for doctors and their patients and their patients in the future. “There will be much more targeted drug development for individuals,” predicts Saggar. “As computer technology gets better we will be able to test an individual’s profile. For instance, around15 percent of the white, European population do not metabolize the drug Codeine. It does not work for them. In this sense, drug marketing will become more targeted.”

The targeting of specific diseases with new drugs based on genomics will likely bring life-changing consequences to those that have been suffering with debilitating illnesses. The reassurance that specific drugs are available will undoubtedly be a comfort to all whether a sufferer or not. “There will be more and more new medicines with mechanisms that will be relevant for specific problems,” explains Zambrowicz. “The availability of these types of medicines will help patients be proactive rather than reactive.”

As with much research, cost is always high and therefore can restrict progress. However, overtime these will fall. “It is only a matter of time before the cost of sequencing a genome comes down dramatically,” says Zambrowicz. “Because of this, people are going to have access to their genome and will begin to know their disease susceptibility, and will be able to work with their doctors before a disease manifests itself. Disease prevention will become a very important aspect of patient care.”

As with most medical landmarks, once society has adjusted to the many benefits they bring, it is difficult to remember how we lived without them. The same is likely to be with the genomics revolution. If genetics can help identify susceptibility to disease, consequently delaying or preventing the onset of any illness then there is unlikely to be any looking back.