By Dzulkifli Abdul Razak
THE power that changes the world through life sciences is the major breakthrough in genetics understanding. Our understanding of genetics could be traced back to a monastery in Brunn, Austria, where an Augustinian (Moravian) monk was experimenting with common garden peas.
Fr Gregor Mendel, who had received excellent training in both physics and chemistry at the University of Vienna, also had a keen interest in botany. He spent many hours tending to his garden and cultivated nearly 30,000 pea (Psium) plants, carefully analysing seed and plant characteristics based on their breeding patterns.
He introduced a quantitative tool to his work, a dimension that was lacking then. He was able to conceptualise the idea of the gene (known as “factor” then) as the unit of inheritance and thus pioneered the study of inheritance.
His experimental findings and discoveries which were recognised after over 30 years (in 1902), turned out to be among the most important advances in genetic understanding.
By 1866, Mendel published in the Proceedings of the Brunn Society for Natural History what were to become his basic laws of heredity based on a series of laws. Based on what he called the First and Second Laws of Heredity, he suggested that “discrete factors” determined the traits and characteristics which would pass from an organism to its offspring. He formulated a simple model by which these laws could operate.
In fact, Mendel’s laws together with Darwin’s theory, gave biology for the first time a potential theoretical platform of its own. Although Mendel’s law was first tested in pea plants, evidence quickly mounted that they applied to all living organisms.
Today, the concept of genetics has become the “power” that could change the world. The achievement is being called one of the most significant scientific landmarks of all time, comparable with the invention of the wheel or the splitting of the atom.
The unveiling of genetic data confirms that there is no scientific basis for the concept of race. People from different racial groups can be more genetically similar than individuals within the same group. Genetic studies show that there is more variability in the gene pool in Africa than outside.
“From a genetic perspective, all humans are therefore Africans, either residing in Africa or in recent exile, “ said Dr. Svante Paabo of the Max Planck Institute of Evolutionary Anthropology, Leipzig, Germany.
Every person on Earth shares 99.99 percent of the same genetic code with all other people. The biological difference between individuals amounts to a fraction of the three billion letters in the human genetic code.
The genetic information will revolutionise medicine over the coming decades, giving us new tests and drugs for previously untreatable diseases.
It could save someone from life-threatening cancer, or could help someone who is suffering from haemophilia, or could produce animals which have the capability to donate organs to people. The potential of this new knowledge will undoubtedly help many suffering from genetically inherited disorders, and diseases. Pigs are already being tested and genetically altered so that their organs may be harvested for use in humans.
As it stands today, the human genome project has made advances far beyond our wildest dreams and with the advent of gargantuan supercomputers, capable of performing billions of calculations per second, the project is progressing faster than ever.
There is little doubt the unfolding of the human genome will benefit healthcare in the short and long term, though many treatments will be costly.
At the nearer end of the time scale, genetic test are allowing people to choose suitable therapies and lifestyles to beat disease.
And in between lie further tantalizing prospects:
¥ thousands of new drugs for previously untreatable diseases,
¥ drugs tailored to individuals, so with far fewer side-effects,
¥ the ability to replace faulty genes,
¥ short-circuiting diseases at source.
In the far future, it may be possible to prevent genetic diseases from being inherited by cutting them out of the gene pool once and for all, so-called “germline engineering”.
Genetic screening
THE first use many new gene discoveries are put to is creating diagnostic tests. For example, haemochromatosis is one of the most common inherited diseases and leads to high levels of iron in the blood. This can lead to organ failure and death by the age of 50.
Previously, diagnosis was only possible by taking a tissue sample from the liver – a painful and risky procedure. Now, however, a drop of blood is enough for a genetic test and regular blood lettings and a careful diet can allow sufferers to live normally.
Many cancers and heart disease are almost certainly influenced by genetic factors, so forewarning patients of their susceptibilities would allow them to make informed lifestyle choices and help prevent future illness.
One key area of flagging up gene defects is the study of single nucleotide polymorphisms (SNPs). These are mutations affecting just one single base pair in a person’s DNA.
They may not cause a disease but may be a very effective signpost for a particular problem, which is why a consortium of major drug companies is spending US$328 million (RM1.2 billion) on tracking down hundreds of thousands of SNPs.
Germline engineering
THE most extreme suggested use for the human genome data is editing the DNA inheritance bequeathed from one generation to the next. Such a scenario involves identifying an abnormal gene and then correcting it in the cells which are used to pass genetic information to offspring – eggs and sperm. No subsequent generation would then be afflicted by their ancestors’ gene defect.
Gene therapy
GENE therapy, using the genes themselves as medicines, is in many ways the most obvious application of the human genome data. But it is also the most controversial, with a number of deaths linked to experimental treatments.
The ideal focus for gene therapy is on single gene disorders, such as cystic fibrosis. Here one abnormal gene can be cut out and replaced by a healthy version, delivered by a tamed virus.
But although over one million people in Britain suffer from inherited illnesses, individually the disorders are rather rare. This means the potential market for a company is small.
Other illnesses known to be caused by faults in single genes include Huntington’s chorea, sickle cell anaemia, and muscular dystrophy. More common diseases, such as cancers, diabetes and schizophrenia, involve complex interactions between genetic faults and so are not so amenable to gene therapy.
Furthermore, knocking out a faulty gene is not without risk – for example, the gene for sickle cell anaemia also gives some resistance to malaria.
Tailor-made drugs
IT is estimated that adverse reactions to prescribed medicines result in two million people in the US being hospitalised each year – 1000,000 of these die.
The difficulty is that every person is unique. So, while a particular medicine may be effective for some people, it could be seriously damaging to others.
The new data about the human genome will begin to make it possible to identify these groups. This would obviously save suffering but even if the drug is simply ineffective for a genetic group, considerable cost savings are possible.
Brand new drugs
TARGETS are what drug companies call the parts of biological molecules they attack with drugs to fight disease, and the human genome information looks like providing more targets than any shooting gallery. Currently, the knowledge of human molecular biology is such that the targets are counted in hundreds but the genome promises thousands.
