The world knew it was coming, that the Book of Life was being decoded at a hectic pace in laboratories across the world. Yet, on June 26, when Bill Clinton and Tony Blair addressed a trans-Atlantic press conference to announce that the Human Genome Project, an international government-funded project, and Celera Genomics, a private US company, have both produced a "working draft" of the 3.1 billion chemical "letters" that contain the entire biological secrets of human life, humanity was stunned. The breakthrough promises startling new medicines and cures for currently fatal diseases (Clinton said that this genetic listing has, at one stroke, added 25 years to the life expectancy of Blair's newborn son Leo.) But it also brings mankind face to face with the sort of future Aldous Huxley predicted in Brave New World: a world peopled with castes created through genetic manipulation, from the ruling Alphas to the slave Epsilons. A cure for cancer and Alzheimer's disease may now be a matter of time but ultimately, this knowledge can also give the power to some future Hitler to create a master race to his own specifications. What is certain is that 20 years from now, life and death will be profoundly different from what we experience. For the lay reader in the year 2000, here is a primer on the new science of genomics.
What is the human genome?
If you thought information science deals only with computers, it's time to think again. Life is essentially about movement and propagation of information. Indeed, we humans are nothing but packets of information. Like all living beings, humans are made up of cells. The nucleus of every cell contains 46 chromosomes. Each chromosome is composed of DNA (deoxyribonucleic acid) and some proteins. Half the chromosomes in any human are borrowed from the mother (23) and half from the father (23).
The Book of Life is written in the alphabet of DNA, comprising four letters-A, G, C and T (the base chemical units, adenine, guanine, cytosine and thymine, which constitute a DNA molecule). Genes are the words and sentences formed from these, the basic units of information that determine how a human being will be and how he will carry out essential functions like digestion, growth, fighting diseases etc. Genes are strings of triplet codes-arrangements of three of the letters A, G, C and T. "Genome" is the complete info-mass (97% of it "junk") in a human body.
What is the Human Genome Project? What's their "working draft" all about?
It's about deciphering the Book of Life. The reading of this neo-scripture began in 1990. The project, involving 16 laboratories in six countries, aims to identify all the approximately 50,000 genes in humans and determine all the sequences of the 3.1 billion chemical bases (units) that make up human DNA.
"The working draft" is the rough sequence of all the letters of the DNA alphabet as they are arranged on human chromosomes. This draft will now serve as the basis for obtaining "high-quality finished sequence" and will also be a valuable tool for researchers hunting down disease genes.
Why is this being called the greatest scientific achievement since nuclear power/antibiotics?
Though this "working draft" is a small, diffident step forward, its implications are stunning. Carried to its logical conclusion, it will beget a whole new biological science. Till now, only a few human genes have been deciphered and there too, not all their resulting functions are clear. Once the project cracks the final sequence, every physiological function, structural detail and behavioural trait of man will have been explained in terms of genetic makeup. This will give us dramatic insights into the causes of currently incurable diseases like cancer and Alzheimer's and lead to revolutionary new medicines across the board. It will be possible to know if a newborn is vulnerable to certain diseases and prepare for preventive action. And, of course, the far-off controversial possibility of parents being able to choose the type of offspring they want.
How do genes work?
The various parts and structure of man are made of proteins-our skin is made of keratin, our muscles and cartilages of collagen and so on. Some proteins are also enzymes that enable essential functions like digestion. Proteins are chains of amino acids. Now each gene is a sequence of triplet codes. Each triplet stands for an amino acid. So each gene is the coded formula (and instruction) for the manufacture of a protein required for a purpose. Thus, genes are like clues to a cryptic crossword. The solved crossword will yield a jigsaw puzzle composed of proteins. Fitting together these pieces will mean the full decoding of the Book of Life.
Are genes the sole determinants of our traits?
The unfolding of human genetics is like a philharmonic orchestra performing Beethoven's Fifth, various instruments either playing together or following and/or chasing one another to create harmony. Simple physiological facts are for sure the result of particular genes. But most behavioural traits and certain special abilities, if at all they can be determined genetically, can't be pinned down to any one gene. In most instances, complex human traits are the result of many genes working in tandem-just like philharmonic musicians. This is known as pleiotropy. Then, of course, there is the environment. In crocodiles, for instance, genes that determine sex are temperature-dependent-a few degrees here and there can produce the difference between a male and a female.
So, who wins, genes or environment?
There can be no winners since this is hardly a race. The right term is probably "interactionism"-that is, neither genes nor the environment can, by themselves, account for what a human being is or can be. American population geneticist Richard Lewontin, British neurochemist Steven Rose and Canadian psychologist Leon J. Kamin argue: "Organisms (read humans) do not inherit their traits but only their genes, the DNA molecules that are present in their fertilised egg. From the moment of fertilisation until death, the organism goes through the historical process of development. What the organism becomes at each moment depends both on the genes it carries and on the environment in which development is occurring." So, two persons with identical genetic makeups in different environments won't develop in an identical way.
What could be the spin-offs of the Human Genome Project, particularly in medicine?
Medical geneticists believe all diseases have a genetic component: inherited, or resulting from the body's response to pathogenic germs (bacteria, viruses) or toxins. Once researchers pinpoint 'errors' in genes that either directly cause or contribute to disease, it will be possible to develop revolutionary new ways to treat, cure, even prevent thousands of diseases (see box).
Can behavioural attributes-alcoholism, violence, etc-be explained in genetic terms?
Public opinion on most such research is unfortunately moulded by the mass media. The demands of a juicy story injects a lot of hype into the findings, often ignoring the fine print in the original reports. For instance, it's been found that if the gene coding for the enzyme monoamine oxidase is faulty, the individual carrying it may be prone to violence. But this enzyme is also responsible for digesting substances found in red wine, cheese and chocolate. So, there are instances where the presence of the faulty gene has led, not to violence, but to high BP, insomnia, agitation after eating certain foods and so on. It's just that the probability of arson and assault in such cases is higher. The media often misses this fine print and reports it as 'Gene for arson found'. The same is true for alcoholism. Essentially, all such genetic studies are based on random sampling and one can talk only probabilistically about these findings without any degree of certitude.
Is there a gene for schizophrenia?
It's coin-tossing probability again. It may-like breast cancer- be influenced by genes in some families but not in others; the environment is also key. There are cases which indicate schizophrenia may have a genetic basis. A small section of the world population has a tiny piece of chromosome 22 missing. This causes all kinds of problems-heart disease, cleft palate, etc. And-it's damp-squib probability again-one in 10 among such people also develops schizophrenia. Screaming tabloid headlines notwithstanding, the schizophrenia gene is yet to be discovered!
Are we programmed to grow old and die?
A theory put forth by Randolph M. Nesse and George C. Williams says certain genes could lead to degeneration when man gets on in years. But they also ensure his survival when he's younger. A gene that controls calcium metabolism, so that broken bones heal faster, could be responsible for slow calcium deposition in blood vessels later in life. The gene responsible for rapid brain growth in humans during evolution from the primates might be manifesting itself as Alzheimer's. Life, it seems, can't do without death.
Are we headed for genetic tinkering to manufacture the perfect human race?
Like nuclear power, genomics has both-to use non-scientific terms-divine and satanic possibilities. When genomics moves out of labs into society, it's bound to become more of a political issue rather than a purely scientific one. If the spin-offs are directed towards therapy, it will be a progressive step. But if the findings are sacrificed on the altar of simplistic, dubious ideologies of racial superiority, genetics will cease to be a modern discipline and will lapse into a pseudo-scientific pursuit of eugenics. That is something future generations will have to take a call on.
