Biological excitement: the international and Australian revolution in genetic science

I can then take a sample of breast cancer tissue and a sample of normal breast tissue, incubate them with the gene chips and see which genes have altered activity in the breast cancer sample, compared to the normal sample. I therefore make no prior assumptions about which gene or genes have gone wrong in development of this cancer and I can also identify new cancer causing genes which were previously unknown. This so-called discovery approach is therefore not limited by previous research.

In addition to identifying all the human genes, a major research effort is being undertaken to catalogue gene variations between different individuals and to correlate these changes with susceptibility to different disorders. Although we are all at least 99.9 per cent identical in our DNA sequence, the other 0.1 per cent still represents about 3 million differences. Some have no known effect; some influence our appearance, our behaviour, our metabolism, our susceptibility to different diseases and our response to medications.

Not only will this individualisation lead to early detection and better treatment of disease but, most importantly, to prevention. Furthermore, knowledge of genetic variation between individuals also promises to explain why some people respond better to certain drugs while others experience side effects. This will lead to cheaper, more effective clinical trials for new medications, better use of existing therapies, more specific targeted pharmaceuticals and the rational use of some so-called “alternative” or “complementary” medicines.

For example, at the Garvan Institute, we have recently signed a formal agreement with the Shanghai Institutes of Biological Sciences to undertake an extensive collaborative program. This program will look to combine Eastern and Western expertise to identify and develop the active ingredients in traditional Chinese medicines for the treatment of obesity and diabetes and to link such research to an understanding of the genes responsible for an effective response to such treatments.

The availability of this amazing database, the Human Genome Sequence, free to researchers around the world, is thus changing forever the way we think about health care. As new targets for specific pharmaceutical development are being identified from gene chip experiments and disease susceptibility and response to treatment being measured at the level of the individual, the focus of future health care will be prevention and personalisation.

From very early in life, we will be able to develop a matrix of our genetic risk for various diseases and act, both through lifestyle and targeted personalised pharmaceuticals, to counter this risk.

This of course is already happening, albeit in a fairly simple form. For example, many thousands at risk of heart disease take cholesterol-lowering drugs; in the US, anti-oestrogen drugs are approved for the prevention of breast cancer in women at high risk of developing the disease. We all justify an extra glass of wine on the basis that the antioxidants help prevent cancer and heart disease.

The technologies central to success in the human genome project, that is, the ability to rapidly determine the G A T C sequence of any DNA molecule, have also revolutionised research in infectious disease. Viruses and bacteria have much simpler, smaller genomes than a human. Their genetic makeup can therefore now be analysed very rapidly. The war against infectious disease will never be won totally, but each battle now should be more decisive and brief.

In the case of SARS, within a couple of months of isolating the virus responsible, researchers had determined the complete sequence of its genetic code, made diagnostic kits to detect an infection, and now have several vaccines in trials.

Stem cells

We have known for some time that every cell contains the complete set of genes, a complete genome. However, it was generally believed that once a cell became specialised during the development of a whole animal or human - that is, it became a blood cell, a nerve cell, a muscle cell - then its programming was locked and it could not change back to an embryonic type of cell capable of giving rise to many types of new cells. Unlike more primitive organisms, it was therefore considered that 'cloning' of higher animals was not possible. Then along came Dolly the sheep, followed by Molly the mouse, rats, pigs, cows, the whole farm.

Certainly, few issues in recent science have generated as much excitement and controversy as the potential use of stem cells to treat disease. The hope of course is that, one day, it will be possible to grow some of your own skin or blood cells in culture, reprogram them to become new nerve or muscle cells, then re-implant them to replace cells lost to Parkinson's or Alzheimer's disease or heart failure or stroke or spinal cord injury. The hope though is still very much a dream.

While few would argue that realisation of this dream is a noble goal, many in our society are deeply concerned about the use of stem cells isolated from embryos. While I believe we would all accept that fertilisation (the coupling of sperm and egg) is a key moment (for some, THE moment) in the creation of a unique individual, Dolly changed forever our view that only by combining genes from two parents can a new individual be formed. Dolly demonstrated that any cell in the body, under certain circumstances, could give rise to a new individual.