Cracking the genetic code

Biology's version of the Book of Life is being written, in part, on the 14th through 16th floors of a gleaming medical tower at Baylor College of Medicine in Houston, Texas.

Most workers are under 30 and hold 'entry-level' positions. Few hold graduate degrees and some haven't finished college. It seems an unlikely setting for what President Clinton in March called 'the scientific breakthrough of the century, perhaps of all time.'

The technicians are nearly finished 'sequencing' the entire human genome; that is, determining the order of the three billion pairs of nucleotides that make up human DNA. The Human Genome Sequencing Centre at Baylor is one of five major sequencing centres in the US, with another in Britain and minor centres scattered around the world. Together they make up the decade-old Human Genome Project, an international consortium directed by the National Institutes of Health (NIH) and the Department of Energy.

Holy grail

The $250 million Project plans to release its first draft by this summer, having sequenced 90% of the genome with 99.9% accuracy. The sequence is on a publicly-available database, allowing researchers to hunt for all 80,000 to 100,000 genes - sections of DNA that are believed to control cell development and operation - in a typical human cell. Scientists use this genetic map to try to figure out what each gene does and how it works with other genes. They then do associate mutations in particular genes with specific diseases.

The sequence of human DNA has been called a periodic table of the elements for human biology, or as a recent Newsweek story gushed: 'the blueprint of human life, the code of codes, the holy grail . . . what it means to be human'. Many believe that this Project will revolutionise modern medicine. The attention over the last few years has sent biotech stocks soaring. The final version, expected two years ahead of schedule in 2003, will be, according to NIH National Human Genome Research Institute director, Francis Collins, a professing Christian, a 'phenomenally significant event in human history'.

Perhaps.

Cures and treatments

Enthusiasts predict that in a few more decades genetic research stimulated by the Human Genome Project will lead to cures and more effective treatments for diseases ranging from cancer to schizophrenia. Involvement in the Human Genome Project 'is a work of discovery which can also be a form of worship', wrote Dr. Collins in 1997. 'It is part of our mandate as Christians to pursue such medical advances, attempting to emulate Christ in his healing role,' he said.

Eventually, goes the claim, once scientists understand how particular genes cause diseases, they will design drugs accordingly, instead of using the current trial-and-error method. Scientists will know why some drugs and therapies work so well for some patients, but put others in hospital. Doctors will prescribe medications with the least unpleasant side effects for a given patient. Some scientists predict designer babies - or at least the ability to influence hereditary traits like height and intelligence and eye colour. In addition, genetic science will produce a host of industrial and agricultural breakthroughs, like toxin-eating bacteria and more pest-resistant crops.

That's the optimistic assessment of the impact of genetic science.

Downside?

But Celeste Condit, a communications professor at the University of Georgia who writes regularly on ethics and genetics, offers a nightmare scenario that includes:

* routine prenatal genetic screening, with stringent standards for determining which babies live and die;

* the ready availability of genetic testing generating a sort of public hypochondria, with fears of disease far exceeding the actual risks;

* genetic discrimination, with jobs and health insurance denied to those at risk of serious disease

* the sorting of young children into career tracks and social classes based on their 'genetic potential'.

At the moment the nightmare seems more real than the dream.

Already, in March, The Daily Telegraph reported a British government agency is calling for genetic screening for all pregnant women, in case 'abnormalities' prompt them to seek an abortion.

Some see prenatal genetic screening as modern eugenics. C. Ben Mitchell, assistant professor of bioethics at Trinity International University in Deerfield, Illinois, said that it 'targets foetuses for destruction, since we don't have cures or treatments for most genetic anomalies.'

At present, genetic testing can provide only a range of probabilities - it can't specify when or even if the patient will develop a given disease. Thus, women who test positive for BRCA1 may never suffer breast or ovarian cancer, but may feel they are walking around with a time bomb.

Who's the father?

Many more bombs, real or not, will be uncovered when genetic testing becomes readily available and people start ordering their own. Already a Houston company has a national advertising campaign for DNA paternity testing. Commuters in 30 major US cities see large, dark billboards with 'Who's the father -1-8-DNA-TYPE' in bold lettering. For $475, Identigene Inc. does a standard DNA paternity test from a cheek swab.

Genetic discrimination is presently uncommon, but a series of horror stories prompted federal legislation discouraging the practice in health insurance plans in 1996 (insurance companies may not consider disease genes a 'pre-existing condition'). In February President Clinton signed an executive order prohibiting it in federal hiring and promotion practices.

But Mr Mitchell believes that if the technology is there, people will find a way to abuse it. 'All of us have some genetic problems', he said, 'and as the tests become more sophisticated, it's unlikely that we'll find anybody without any mutations.'

Gene therapy?

The ethicist is also concerned that economic pressure to get genetic tests and therapies to market are tempting scientist-CEOs and their venture capital backers to ignore or marginalise once-inviolate research principles and hide information that would drive down the stock prices of their biotech firms.

In the most damning incident so far, Jesse Gelsinger, 18, died in a gene therapy experiment for his genetic liver disorder at the University of Pennsylvania. The Food and Drug Administration shut down the programme indefinitely, blasting researchers for failing to halt the study when several patients suffered serious side effects, failing to report these incidents to the NIH, and failing to obtain proper consent from patients. The NIH later discovered that gene therapy researchers across the country had not filed reports on 650 'adverse incidents' in a timely fashion.

Patents

The dispute over ownership of genetic data is also troubling. Celera Genomics Corp., a private firm, is racing the publicly-funded project to finish the first genetic map. It developed a powerful new 'shotgun' sequencing method that is still controversial because it leaves large gaps - like having all the pieces of a jigsaw, but not being able to assemble them. Celera has already produced its first 'draft' of the human genome. Celera and HGP officials were negotiating a collaboration that might have produced a final version by the end of this year. Talks broke down in March over whether the sequence would continue to be freely available or whether Celera could control the data, turning biology's Book of Life into a for-profit lending library. Celera now sells its genetic data to subscribers, mostly pharmaceutical and genomics firms.

Defenders of public access say that the human genome is the common property of humanity. Charging for access to the sequencing data will stifle genetic research, they say, and there's too much at stake to allow that. Moreover, the drive to patent genes is turning into a modern-day gold rush. The chemical sequence of DNA may not be patented, but individual genes may if the gene's function is known. Billions of dollars are at stake.

Christians should start now to influence the public debate over genetic ethics. The main issues involve privacy of genetic information (should your employer or the government know you're susceptible to hypertension?) and how much genetic manipulation is appropriate.

Questions abound. What's morally wrong with giving your child a better memory? Would you marry someone with a genetic predisposition to Alzheimer's? Should you ask for premarital testing?

Who knows?

Stymied

Less may be possible than the promoters of genomics predict. After a decade of research in gene therapy, individual patients have been helped in trials, but there is still scant evidence that gene therapy can effectively treat any disease. Researchers have been stymied by the body's immune system, which attacks the viruses attempting to insert the 'healthy' genes.

Nobody knows which human characteristics are genetically determined and which are affected by environment or other factors.

Jonathan Wells, a molecular biologist with the Discovery Institute, argues that genes, environment and cell structure all affect development. DNA controls the production of proteins that affect development, but the cytoskeleton (a network of microscopic fibres) and certain features in the cell membrane determine what happens to these proteins after they are made.

This helps explain why, when the 'developmental genes' from a fruit fly are inserted into a mouse embryo, it continues to develop along mouse-embryo patterns, until the lack of the correct protein kills it. 'It would be more accurate to say that a developmental programme is written into the structure of the entire fertilised egg, in a language of which we are still largely ignorant,' he said.

'The notion that genes control development is a fall-out from neo-Darwin evolutionary theory', Mr Wells added. Evolutionists use genetic mutations to explain how organisms could change gradually over time. But if development involves the entire egg, then its complexity is much stronger evidence that a Creator designed life,

Correlations

Mr Wells also questions whether genes determine most diseases. Some single-gene disorders, like cystic fibrosis, clearly are mainly genetic, he said. But the only way researchers can now connect a disease with a particular gene is by statistical correlation studies - that is, they hunt for common genetic patterns in people with the disease. 'But correlation is not cause' he pointed out, 'and the correlations aren't even very good in many of these cases.'

If many factors - in addition to DNA - do affect diseases, they would help explain why only some of the people with the gene for a given disease actually develop it, and why severity varies wildly among people with the same gene. The claim that diseases are the result of interaction between genes that have yet to be discovered 'is still only a theory', he said.

Whatever else might be said, sequencing the human genome is a much smaller advance than its promoters claim.

Reprinted from WORLD magazine, Asheville, North Carolina, April 29 2000 issue, with permission.

The implications of the end of the Human Genome Project (reprinted from World Magazine)