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DNA deciphered, next stop wonderland?

Md. Asadullah Khan
****June 26, 2000 ... an international group of public-sector scientists, working on the 300-million Human Genome Project, announced that it had 'assembled a working order of the human genome - the genetic blueprint for a human being." The "first technological triumph of the 21st Century , achieved by some 1,100 biologists, computer scientists and technicians working in Britain, France, Japan, United States, China and Germany for over a decade, has opened up an avenue fantastic medical advancements. However, there are sombre moral concerns, too, ***
****Researchers are now convinced that with this profound knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on our lives ae and even more on the lives of our children. It will revolutionise the diagnosis, prevention and treatment of most, if not all, human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer's, Parkinson's, diabetes and cancer by attacking their genetic roots.****
****But this increasing knowledge of the human genome, celebrated scientists like Dr Collins and Dr Craig Venter cautioned, never change the basic belief on which our ethics, our government, our society are founded. All of us are created equal, entitled to equal treatment under the law. After all one of the great truths that has emerged from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 per cent the same.***
Il all began at a place called Brno, now part of the Czech Republic, nearly one and a half centuries back. A Moravian monk called Gregor Mendel, while carrying out cross-breeding experiments on peas, made two astonishing discoveries: first, many characteristics are Inherited in an all-or-nothing way: and second, cross-breeding can cause a characteristic disappear for a generation. Although his findings, published in a local naturalhistory Journal in 1866. were largely Ignored for than 30 years, they heralded the beginning of man's quest for the secrets of his own existence.
Eighty-seven years later. In 1953. American biochemist James D Watson and British biophysicist Francis Crick announced their discovery’ of the double-helix structure of DNA. the molecule that carries the genetic code. And 37 more years later, the Human Genome Project (HGP). involving scientists from Britain. France. Japan. United States. China and Germany, was launched in 1990.
Now. over a decade later, scientists possess the knowledge that can change the course of human civilisation.
“The human genome sequence vill be the foundation of biol-ngy for decades, centuries and millennia to come." says John Sul-stan. director of the Sanger Centre, a genome lab near Cambridge. England.
“That the human genome has been completed at the start of a new century’ has a pleasing poetry to it." wrote Geoffrey Carr in The Economist. "For genomics has brought the science of biology to a new threshold. And it may well have brought medicine, agriculture. industry and even philosophy to a new threshold too."
For about 3.2 billion letters encoded so far, each letter represents a molecule ae adenine, cytosine, guanine and thymine (generally referred to by their initial letters A. C. G and T). Every cell of every human body, from skin to muscle to liver and everything Ui between (except red blood cells), contains a copy of the same DNA. The human genome sequence is like a complex instruction manual of genes that governs human biological functioning from the moment of conception to death.
But this increasing knowledge of the human genome, celebrated scientists like Dr Collins and Dr Craig Venter cautioned, never change the basic belief on which our ethics, our government. our society are founded. All of us are created equal, entitled to equal treatment under the law. Alter all one of the great truths that has emerged from this triumphant expedition inside the human genome is that in genetic terms, all human beings, regardless of race, are more than 99.9 per cent the same.
Explaining this Dr Venter said in the International Human Genome Sequencing Consortium meeting arranged on June 26 this year that the method used by Celera. a privately funded company. has determined the genetic code of five individuals. They have sequenced the genome of three females and two males, who Identified themselves as Hispanic. Asian. Caucasian or African-American.
"We did this sampling not in an exclusionary way. but out of respect for the diversity that is America, and to help illustrate that the concept of race has no genetic or scientific basis." Dr Venter said. "In the five Celera genomes, there is no way to tell one ethnicity from the other. Society and medicine treats us all as members of populations, where as individuals we are all unique and population statistics do not apply."
A gene is an instruction, like the directions in a bead-making kit but written in molecule-ese. Humans have perhaps 80.000 genes and we are 99.9 per cent identical. That is only one in 1000 chemical letters does the genome of say Rahim Baksh differ from that of Abdul Karim.
Encouragingly, the "working draft" sequence released on June 26 has proved, Viable .^.Identifying.genes for breast c^qcer susceptibility (BRCA2). hereditary deafness (Pendred Syndrome), several hereditary- skeletal" disorders, haemorrhagic stroke, a puzzling kidney disorder that can lead to end-stage kidney failure. hereditary epilepsy and one type of diabetes. Strangely though. June 26 morning that brought to the world a triumphant news in the field of genetic research coincided with a personal
tragedy for Dr Collins, director of the publicly funded genome research project in the US. Collin's contribution to the sequencing task was most noteworthy.
"Less than 24 hours ago." Collins told the gathering. "I attended the funeral of my beloved sister-in-law. a wonderful marionette artist who brought magic and joy to thousands of children with her art. She died much too soon of breast cancer. The hope and promise of understanding all of the genes in the genome and applying this knowledge to the development of powerful new tools came just too late for her.”
In addition, in clinical trials is a drug for leukaemia that was developed on information in the sequence. Preliminary reports about the drug are very positive.
Dr Craig Venter, president and chief scientific officer of the Celera Genomics Project, a privately owned genome research firm in the US. says. "We are learning the language in which God created life. We are gaining ever more awe for the complexity, beauty, the wonder of God s most divine and sacred gift ."
Venter and other researchers are now convinced that with this profound knowledge, humankind is on the verge of gaining immense new power to heal. Genome science will have a real impact on our lives at and even more on the lives of our children. It will revolutionise the diagnosis, prevention and treatment of most, if not all. human diseases. In coming years, doctors increasingly will be able to cure diseases like Alzheimer’s. Parkinson’s, diabetes and cancer by attacking their genetic roots.
To cite an example, patients with some forms of leukaemia and breast cancer already are being treated in clinical trials with sophisticated new drugs that precisely target the faulty genes mid cancer cells, with little or no risk to healthy cells.
US President Bill Clinton said at the launching ceremony of HGP findings. "It Is conceivable that In fact our children's children will know the term cancer only as a “constellation of stars."
In a wonderful spirit of co-operation, both public and private ventures towards the end ol this year will examine what scientific insights have been gleaned from both efforts and how the prudent world can most Judiciously proceed toward the next majestic horizons.
The next step for the genome project, as Dr Venter and Dr Collins indicated, would be completion of a virtually error-free final draft of the human genome before the 50th anniversary of the discovery of double helix, less than three years from now. Dr Venter further stressed that through sustained and vigorous support for public and private research, efforts must be made to sort through this trove of genomic data to identify every human gene. This effort will enable researchers around the globe to discover the function of these genes and their protein products and that will help them effectively and rapidly to convert that knowledge into treatments that can lengthen and enrich lives.
But before ail these can be achieved, it must be emphasised that biotechnology companies are absolutely essential to make this endeavour a success. For it Is they who will bring to the market the life-enhancing applications of the information from the human genome and that calls for long term investments that will change tire face of medicine for ever.
There are ethical, moral and spiritual dimensions to the power of knowledge the scientific world now possesses. Illustrious genome researchers like Venter and Collins have called upon the leaders of the developed world and business entrepreneurs to make sure that this new genome science are directed toward making life better for all citizens of the world, and never Just a privileged few. And only on that consideration Collins in recent
times rebuffed an offer from the biotech firm Celera to join forces and speed up the work: he feared Celera would keep the results private, available only to those who pay. for too long.
Undoubtedly, with knowledge of our genetic code will come the power to re-engineer the human species. But biologists must not use the genome as a parts list much as customers scour market to replace a broken piece of a household gadget or chinaware.
As the researchers unlock the secrets of the human genome, there are practical concerns that continue to haunt the society. Concern has been expressed if we can ensure that new discoveries never pry open the doors of privacy. How can we guarantee that genetic information will not be used to stigmatise or discriminate any individual or group? ^tj «#
From the inception of the genomic project, ethical warned that genetic knowledge would be used against people in insurance and employment. Surveys in the developed world have shown that some problems in the meantime have cropped up.
Ann Miscoi in a state in the US underwent genetic test and learned that she carried a marker for the blood disorder
haemochromatosis. Although she was being successfully treated. Jier insurer did not turn up to foot the fill. The Job offer for another person in North Carolina who was otherwise healthy but carried a gene for kidney disease was withdrawn. More shockingly. Beatrice. 40. was fired from her Job after she tested positive for the genetic disease that killed her brother.
However. 39 states in the US have so far prohibited at least in part discrimination in health Insurance based on genetic tests and 15 have some ban on discrimination in employment. Worryingly still, a 1999 survey by the American Management Association found that 30 per cent of large and midsize firms obtain such information on employment.
The genome sequence represents a new starting point for science and medicine, with potential impact on every disease. Approximately 2000 people die in America alone from cancer. As a consequence of the genome efforts and the result that will be catalysed by this information. Venter "humbly said. "There is at least the potential to reduce the cancer deaths to zero during our lifetimes." But the development of new therapeutics will require continued public Investment in basic science and the translations of discoveries into new medicine by the biotech and pharmaceutical industry. Pharmaceutical companies are now looking froward to harnessing the research to create a new generation of drugs targeted specifically to Individuals. In the scientific world the next race would be using the genome map to discover which disease is caused by which specific gene.
The human genome project not only holds promise for a healthier living, but It holds bright hope for disease shields. Other than the fact that the genome code will pave the way for understanding as to how genetic diseases like cancer and diabetes work, it will now help us to determine genes that will revert cancerous cells to normal. With CoUins-Venter parallel research work on human genome project reaching a successful completion. there Is now hope of course, that genetic science could be used to fix health problems, not Just to predict them. Since genes direct the assembly of every cell in the body, it should be possible to treat chronic health problem by slipping corrective genes into patients. But getting the body to adopt and express therapeutic genes has been an enormously difficult Job so far. The most common vector a- a cold virus or adenovirus ar sets off an immune response that destroys the needed gene and can endanger the patients.
Encouragingly, now there are simple ways to harness DNA.
At Maryland-based Genome sciences researchers are splicing human genes Into bacterial cells that can be grown In culture. The cells then churn out proteins that can be given to patients as drugs. One of the company's product. MPIF-1. could help protect bone marrow cells from toxic effects of chemotherapy. Another protein called KGF-2 may speed wound healing. These drugs arc still on clinical trials but oncologists arc already using similar agents to replenish Immune cells decimated by chemotherapy.
A Californian breast cancer patient Ginger’s trauma and pain Is worth listening to. Her breast cancer had spread to an alarming extent invading her lymph nodes and liver by the time it was diagnosed and conventional treatment could not help her. Desperate for life, the 50-year old public health nurse called UCLA from her home if she could Join a clinical trial. Incidentally, Dr. Dennis Slamon was using a genetically engineered antibody called Herceptin, which blocks the HER-2 receptor protein that dots the surfaces of breast cells. When tests showed that Ginger's cells were swarming with the rogue protein, she was in. Her tu-
mours shrank by a stunning 25 percent over the first year. So the researchers kept treating her. After three and a half years of weekly injections, the tumours had essentially vanished. Says Ginger. “My lesions were so small that doctors couldn’t tell whether they were cancer or scar tissue." The drug may not still be a panacea but it stands as an emblem of how understanding the genome could advance the art of medicine.
But the most worrying problem that emerges in a few' decades from now is the prospect of having designer babies through the tool of genetic engineering who will be cured of all possible genetic defects even before they are born. This technological tri-umph will bring in two classes of humans: "the naturals" and genetically enriched". But the rainhkaUons would be far-reaching invoking ethical and moral Issues, because having extra choices can sometimes be very oppressive.
It is an ethical quandary and an economic one. about fairness and fate, about Vanity and values. Which side effects would we tolerate? What if making kids smarter also made them meaner? What if only the rich could afford the advantage?
Says bio-ethicist Arthur Kaplan of the University of Pennsylvania. "If you wait, five years from now the gene doctor will be hanging out the MAKE A SMARTER BABY sign down the street." Sure enough, doctors can screen foetuses for genetic diseases like cystic fibrosis and Duchenne muscular dystrophe and one day they may be able to treat them in uterus. But correcting is one thing, perfecting is another. If doctors can tinker with a gene to help children with autism, what’s with other genes to make “normal" children smarter?
Says Thomas Murray, director of the Hastings Centre (a bioethics think-tank), "If you make a change in one area, it may cause very subtle changes in some other area."
What if it turned out that by enhancing intellectual ability, some other personality trait changed as well?
"Everything comes at a price." says UCLA neuro-blologlst Al-cino Silva. “Very often when there is a genetic change where we improve something, something else gets hit by it."
So it is never a clean thing. The broader concern is one of fairness. Will such enhancement be available to everyone or only to those who can afford it?
"Sure enough, every parent in the world is going to want this." says bio-ethicist. "But who will have access to it?"
It will create a new form of discrimination.
How will we look at those who are not enhanced, the child with low IQ? Will a child one day be able to sue his/her parents for failing to do every thing they could for her?
That means, "we must not play God". All of us must ensure that the human genome be used freely for the common good of the whole human race, to ensure that the powerful information now at our disposal is used to transform medicines, not abused to make man his own creator or invade individual privacy.
The author Is Controller of Examinations, BUET.