Feature

Gene Genies

Opening the "magic bottle" of human genetic material has the potential for use and abuse.

Dr Geoffrey K. Chambers

Recent years have seen an unprecedented increase in public awareness of genetic issues, primarily through the impact of the technology itself, whether through the role played by DNA profiling in the capture of the South Auckland rapist, the notorious twin trials of O.J. Simpson or debates over human cloning.

New public consultation initiatives run by government departments and others have highlighted many areas of social concern and many novel views. The debate continues through conferences, such as the Health Research Council's meeting on human genetic information; legislation, such as the Criminal Investigations (Blood Samples) Act; and through the media, such as the coverage given to the possible uses and abuses of cloning technology for humans.

The Human Genome

Every human cell contains sufficient genetic information to make and operate an entire human being. This information is stored in chemical form as DNA molecules packaged into structures called chromosomes in the cell nucleus. In DNA molecules a linear sequence of molecular units called nucleotides or bases encodes this information. The units are represented by the symbols A, C, G and T.

It takes a great deal of information to specify plans for a human being, but scientists working on the Human Genome Project have already begun the awesome task of acquiring and decoding all of the DNA base sequences in the human nucleus.

How much information will they need to collect? Huge amounts! The human genome contains three billion As, Cs, Gs and Ts, enough to fill 30 bookcases each holding 100 books containing 1,000 pages with 1,000 symbols per page. It will take a long time for someone to read all these books, and even longer to understand what is written in them, but biologists believe that it will be possible to do so and that much of value will be learned in the process.

Studies involving many volunteer subjects will be required to collect DNA sequences which represent the wealth of genetic diversity in human populations worldwide. The independent international research programme which aims to do this is called the Human Genome Diversity Project.

The importance of this project can be understood by considering a simple statistic. If we carefully compare DNA loaned to us by two individuals taken at random from the New Zealand population we would find around 5 million DNA sequence differences between them. It is likely that some of these differences could be associated with important genetic traits such as resistance to disease. Therefore, comparisons between DNA sequences obtained from many different people may lead to significant medical advances.

Genetic Identification and Screening

Because different people have very different DNA sequences in their genomes, it follows that there must be some chemical analysis which is capable of distinguishing them as individuals. This is the basis of those techniques which have come to be known popularly as DNA fingerprinting, or more correctly as forensic DNA profiling.

If the genetic differences which exist between people were evenly distributed we would expect to find two differences per page in our imaginary human genome library. In fact, what we find is that the differences tend to be rather clustered, crowding together by tens and hundreds on particular pages of particular volumes. What modern forensic techniques do, in effect, is to find those volumes and pages and present a summary of the information contained there in the form of bands resembling a supermarket bar code.

Our new-found ability to identify people from small biological samples has many positive applications, such as for crime detection or for identification of missing people killed in accidents, natural disasters or battles. However, it does present society with serious dilemmas about how far we may be willing to intrude into people's privacy in order to achieve these ends. The Criminal Investigations Blood Samples Bill gives the New Zealand Police power to obtain fingerprick blood samples from suspects and to keep a DNA database of profiles for identification of repeat offenders.

In my experience, no responsible scientist doubts the reliability of the forensic technology, and few people doubt the need for some form of compulsion to be applied to reluctant suspects in serious crimes. It is also true that under the bill blood samples would only be taken under court order and under strict supervision. However, many people believe that this form of compulsion is going too far. Others, including the Privacy Commissioner, are concerned about potential abuses of DNA databases. These issues have been aired in public submissions on the bill and in a Privacy Issues Forum.

As more and more human genes are discovered, scientists are beginning to identify genetic defects that cause diseases like cystic fibrosis, diabetes and breast cancer. It is now possible to offer genetic screening to detect genetic conditions before they cause problems (such as breast cancer), and to deliver genetic counselling services to affected families in the form of discussing preemptive surgical options.

Providing adequate public access to this technology presents many difficult problems in a country with a population as small as New Zealand's. The tests themselves are usually expensive. This is because they are complex and often require participation from several family members. Results need expert interpretation and must be delivered to patients with counselling and supported by back-up services. There are literally thousands of known heritable genetic disorders and almost all of them are extremely rare. In practice this means that very large amounts of resources have to be devoted to very small pools of patients.

In my view, New Zealand does not have a particularly good track record in providing medical genetic services. This unfortunate situation does not seem to have arisen from a lack of dedicated and talented analysts, but rather from a long-standing failure to support them properly. In 1993, this culminated in the resignations of two of New Zealand's total of three specialist geneticists.

Since that time the situation has begun to improve. New service staff have been appointed and together they published an important report entitled Priorities for Genetic Services in New Zealand, laying out specific recommendations for clinical, laboratory and screening services. The Maori caucus at the Health Research Council conference called for the rapid development and establishment of genetic services for Maori which would provide them with appropriate options, and for greater involvement of Maori in biomedical research.

If the advice of the specialists is followed, medical genetic services will benefit and tests will become more widely available. This will be of unquestioned value for many parents and children who are at risk of genetic disorders. However, other non-medical organisations may also be tempted to use this technology and, as many fear, use it for discrimination. These organisations have been suggested to include insurance companies and employers.

The potential uses of genetic screening tests by these two groups was discussed at the Privacy Issues Forum and at the HRC conference on human genetic information. The consensus coming from these meetings is all good news. Employers are not presently interested in screening their employees, and insurance companies do not plan to require that their clients undergo genetic tests in order to obtain cover. Instead, insurance companies will adopt what they call a "balanced approach", requiring only that clients make a full declaration of any pre-existing genetic condition that they are aware of. This is necessary to protect the companies (and their honest clients) from those individuals who might seek to exploit their private knowledge concerning a medical condition in order to obtain a high insurance payoff for their heirs.

These public discussions on genetic screening did reveal some interesting new problems that will require careful thought. In particular, it is becoming clear that conventional Western concepts of privacy begin to break down in the face of genetic information. This is because knowing things about your own genes allows you to infer things about the genetic makeup of your close relatives. It seems likely that the traditional Maori approach of seeing genetic information (ie one's whakapapa) as communal property will be more helpful in this regard.

Appropriate Uses

People have expressed concern over the therapeutic uses of human DNA -- those techniques in which one person's DNA is used to cure a genetic defect in another person. This "gene therapy" causes relatively little alarm when it is achieved by delivering donor genes directly to a willing recipient, such as by providing genetically modified immune system cells by bone marrow transplant.

However, other methods may be less willingly accepted. For instance, it is now possible to transfer human genes to animal cells or even to create entire "transgenic" animals which have active human genes transplanted into their DNA. In the language of biotechnology, such creatures are known as "animal bioreactors". They can be farmed economically to produce pharmaceuticals like insulin for diabetics. It is clear that many people find the idea of placing human genes into animals deeply offensive, and the Minister for the Environment has twice rejected an application from a UK company to breed transgenic sheep on a New Zealand property.

Several well-organised groups of indigenous people around the world, including some Maori in New Zealand, are strongly opposed to the Human Genome Diversity Project as originally planned. It is regrettable that this issue should have become so strongly politicised, because activists and scientists now seem to hold almost identical positions on the ethical safeguards which should accompany sample collection.

The activists' concerns actually go much further than this. They raise three main objections. First, the project is seen as the ultimate stage in colonialism. In other words, they fear that once DNA samples from an indigenous people have been banked, there is no longer any incentive to preserve the people themselves! Second, scientists may patent genetic information obtained from blood samples and not wish to share the profits with the original owners. Third, regardless of the potential long-term benefits, sophisticated academic exercises, such the Human Genome Diversity Project, are not a priority for most indigenous people. They are much more concerned with problems which have a direct impact on their basic living standard, such as land rights and health care. The Maori caucus at the HRC conference rejected the Human Genome Diversity Project and called on others to do likewise.

The Health Research Council of New Zealand, the Privacy Commissioner's Office and other New Zealand organisations are to be congratulated for bringing issues in human genetics to the attention of the New Zealand public. There are many important concerns to be faced and resultant problems to be solved. Some of these arise from inherently different cultural viewpoints and some from misinformation. The remedy for both is obvious; continued and energetic dialogue involving all interested parties.

Dr Geoffrey K. Chambers is a Reader in biochemistry, molecular biology and genetics at Victoria University.