Genes and ownership: a scientific approach

So far, the debate about genes and ownership has been centred on the economic consequences of scientific discovery. The scientific concepts are taken for granted, but not always proven or even understood. But before discussing ‘to whom those genes belong’, it is important to consider the basis and relevance of genetics in human biology and physiology, and the possible use of genetic information.

The science behind genetic testing

It is a commonly held belief that knowledge of the human genome will open the door to an extraordinary range of possible medical advances, both preventive and curative. This remains to be proven, or at least to be carefully evaluated.

How often have we heard of a new genetic discovery or biological revolution that would cure the world of disease? Consider the discovery of interferon in the 1960s, then a newly identified molecule that was supposed to cure many diseases, including cancer. Nowadays, however, it is acknowledged that while interferon is a useful molecule in some diseases and for some specific applications, it is not the panacea it was thought to be. Likewise, the human genome could lead to new possibilities. But we have great expectations that might not materialise.

Technically, there are a few limitations that must be considered. Celera, a private company, and the Wellcome Trust, part of the public Human Genome Project (HGP) consortium, have both published their sequence of the human genome. But whose genome is it? Whose DNA was used? How representative of the human species is this DNA? The Celera paper indicates that five individuals (two males and three females – one African–American, one Asian–Chinese, one Hispanic–Mexican and two Caucasians) were used, while the HGP paper based its work on at least two individuals (one male and one female). Scientists are well aware of the influence of ethnic origin in the development of pathologies and this is something we cannot neglect. The resulting sequence could only be representative of a minority.

Inter-individual variations are common and natural, raising questions around the determination of the final sequence. More importantly, the sequencing must be repeated several times to make sure that the sequence has been properly read. Initially, Celera planned to generate its own sequence with a ten-times coverage but ultimately the sequence was only covered five times, with several gaps. Ironically, the Celera sequence, whose quality has been questioned, borrowed significantly from the sequence simultaneously published by the HGP consortium and available in the public database.

If an agreement is reached and a sequence of reference is agreed, ‘the real challenge of human biology’ as emphasised by Venter’s team, ‘beyond the task of finding out how genes orchestrate the construction and maintenance of the miraculous mechanism of our bodies, will lie ahead as we seek to explain how our minds have come to organise thoughts sufficiently well to investigate our own existence.’

The meaning of a genetic sequence

Tom Miller underlined the difference between a disease and the genetic susceptibility to a disease. This is something that even respected scientists, prisoners of a gene-centric view as described by Michael Ashburner, fail to recognise or willingly ignore.

It is important for both the public and the polity to understand that genetic susceptibility does not mean disease certainty. A genetic susceptibility is an increased risk of developing a disease due to the presence of a specific pattern of genetic information. In other words, in actuarial words in fact, it’s nothing more than a percentage. This genetic susceptibility should not be mistaken with diseases resulting from direct genetic anomalies. In this case where the development of pathology is anticipated and ineluctable, science can provide an insight, but medicine remains powerless.

99.9% of genetic information is common to every human being. It is the remaining 0.1% that contributes to some of our external and internal particularities, such as eyes and hair colour, but also susceptibility to disease. That scientists, backed by private investors, want to reveal the mysteries of this 0.1% of genetic information is laudable, but it won’t be enough to elucidate the susceptibility of an individual to a disease nor will it bail us out of illnesses.

The environment both inside and outside our body has an influence on the pathologic process. Cancer for instance is rarely a familial disease. This should be understood to mean that cancer might run in a family but that most cancers are not inheritable. In fact, most cancers (90% in the case of breast cancer and prostate cancer) are not familial, suggesting that if genes have their role in the development of the disease it is not enough.

Diet is an obvious example of the importance of external factors affecting the normal function of our body. The Parsi Women of India show a higher rate of breast cancer when compared to other Indian women. It was believed that a genetic difference was responsible, but a closer examination revealed that the Parsi people have a lifestyle similar to westerners, with the corresponding risk of women developing breast cancer. This does not exclude a role for genes in the development of the disease, but limits it to a determining factor within a wider context.

The role of our environment and the speed at which it changes and acts upon us is even more striking. During the last century, our environment has changed dramatically and much faster than our genes. Genes that were useful a century ago, when life’s conditions were harsher, have become somewhat useless and in some cases damaging to our more sedentary lifestyle. This situation can change again, providing a new meaning for our genetic identity.

The meaning of our genetic inheritance is ever changing. It depends on circumstances, people and their environment. Genetics testing can only provide an imperfect and provisional image of who we are and what we could become.

What role for genetic screening?

It is clear that knowing our genes will be an important aspect of future research, but this does not mean that this knowledge will or should change our lives. If it were to do so, it is important to understand what could change and how.

Many studies have succeeded in establishing a correlation (a very important word not to be mistaken with ‘causation’) between a genetic profile or pattern with a specific disease. It is here again important to keep in mind that most diseases are not characterised by one genetic pattern (with the exception of single-gene disease). The political and medical worlds have now to decide what to do with such information. Will it be used to cure the disease, or to prevent it – the ultimate form of prevention being the abortion process.

The development of genetic testing now available over the counter represents a serious danger for the future of mankind. An uninformed public could easily be misled by the results of a genetic test whose meaning remains unfathomable. Most importantly, genetic testing is bringing back the eugenic issue, although so far, we haven’t heard much about it. Neither scientists, nor doctors nor the politicians dare raise the debate in those terms. If genetic testing for various diseases was widely and easily accessible, and parents could be given a chart of the ‘possible’ life of their progeny, what would they do? Would they take the risk to have a child with a high risk of coronary disease or would they choose to discard any unsatisfactory embryo? One might note in passing that the development of genetic testing and embryo screening could rapidly lead to the end of a costly but rather ineffective gene therapy, since there would be very few diseases to cure.

The possibility of knowing what could happen to us because we know ‘our genes’ opens up some interesting questions. Will the use of genetic testing assist individuals in making lifestyle plans and choices? I do not believe so, unfortunately. For instance we know that smoking causes cancer, but does that stop people smoking? We know that a healthy diet is our best protection against coronary heart diseases as well as obesity, but does that stop us eating junk food and drinking soft drink?

Before asking what we would do if we knew, we should ask first if we would like to know, and why. This is a personal choice to make and a personal decision to take. If an individual refuses to know her/his possible forthcoming health problem, what right would any authority (employer, insurance company) have to impose the burden of this knowledge on an individual? Genetic knowledge here conflicts with privacy rather than ownership.

Knowledge of our genome does not come complete with miraculous solutions to our troubles. For instance, the publication of the complete genome sequences for the human parasite responsible for malaria and its vector, the mosquito Anopheles gambiae, will ‘provide little relief to those suffering from malaria’ according to the team who performed the sequencing. ‘What we shouldn’t do is to get carried away with the glamour of it all and spend a lot of money on it. It would need maybe $450m a year to provide nets and insecticides for all of rural Africa. A lot of money. But what’s spent on insecticides against cat fleas in the US is twice that. And cats don’t even die of it,’ said Professor Curtis, of the London School of Hygiene and Tropical Medicine.

Genetic testing could prove useful for the early diagnosis of diseases. However, it is a first step and there will still be a time lag between the development of diagnostic tools and new therapies. This time lag could be longer than expected, as rational design of new drugs has proved rather unsuccessful so far. In the absence of proper treatment, genetic testing provides information that is not always wanted or useful.

Genetic testing: where the money is

There is a legitimate interest in knowing the maximum amount of information that could prevent the occurrence of a disease or improve its treatment. This is not a new idea or concept. Many biochemical factors are commonly used to detect a disease that hasn’t obviously showed up, and many are used to assess the efficiency of a therapy. The difference between a genetic marker and a biochemical one is that the former is an indicator of susceptibility, when the latter is an indicator of a pathologic state.

This is where the money is – in the development of tools that allow the early detection of a disease in susceptible subjects, tools that can predict the outcome of a therapy or the development of new drug therapy. For these challenges, access to the human genome is fundamental.

The development of diagnostic and follow-up tools based on genomic information consists of the identification and characterisation of genetic sequences believed to be involved in the pathologic process. The technology used for this involves both the identification of the genes and the analysis of their sequences.

Then there are two possible approaches for the development of new drug therapy. The first, pharmacogenomics, is based on the study of how an individual’s genetic inheritance affects the body’s response to drugs. Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each person’s own genetic make-up. The second approach is based on the knowledge of the specific pathways and molecules involved in a disease and the development of drugs specifically targeting these molecules and this pathway.

These technologies have their critics, who remain doubtful about their efficiency and just how realistic they are. Such technologies also suppose that the Department of Health will be able to support the cost of personal medication, which in the present situation is very unlikely.

However, the pharmaceutical industries are aware that they can make a lot of money developing these tailor-made drugs, and it is in their interest to convince us of their potential even when science and common sense challenge their worth. As a consequence, vast amounts of money are invested in ‘borderline’ technology, when investing in basic education and prevention could prove to be a better investment.

Conclusion: who should own what?

The Nuffield Council on Bioethics recently published a discussion paper about the Ethics of Patenting The Council distinguished four different uses for DNA sequences: (1) diagnostics, (2) research, (3) gene therapy and (4) therapeutics. The general conclusions of the Council are that patents that claim DNA sequences should rarely be granted. The only exception is for patents that claim DNA sequences that are used to make new drugs (such as insulin or erythropoeitin).

It seems legitimate that the tools developed by the private sector can be patented even if they are based on public resources. Otherwise, further developments will be greatly slowed down. However, patenting shouldn’t restrict the patient’s and doctor’s right to perform genetic testing.

This is what is happening with the BRCA2 gene and breast cancer screening. Myriad Genetic Laboratories, which owns the patents on the breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2, charges $2,580 for patient-requested BRCA DNA sequencing and mutation analysis (BRCA gene mutations are estimated to cause 7–10% of all breast and ovarian cancers). In an attempt to defuse critics of the company, Myriad Genetic Laboratories has struck a deal with the US National Institutes of Health (NIH) for cut-rate prices. In exchange, Myriad is looking forward to more studies of the BRCA genes using its tool. This would provide information about the effects of specific BRCA mutations and how BRCA mutations may correlate with cancer treatment outcomes. However, Myriad’s patent has recently been challenged by a Maltese biotechnology, Synergene, that will launch a diagnostic test for breast cancer next January.

Our genetic information could legitimately be perceived as being part of our individual inheritance. Like our material possessions, the members of our family inherit it. UNESCO regards the human genome ‘in a symbolic sense as the heritage of humanity,’ others as the ‘common heritage of humanity/mankind,’ or as ‘collective’ or ‘general property,’ or finally, as our ‘common heritage’ and the ‘prized possession of all humanity’.

Whatever we decide about the ownership of our genes and the applications based on them, the next step will be to reach an international consensus. The present international situation is rather confusedand this is an issue in the hands of governments and international organisations. In 1998 the European Parliament adopted a directivethat was a landmark in the debate about genes patenting. However, this Directive does not resolve all the issues. An international consensus remains to be reached.

Meanwhile, it is important that all the contributors to the debate not only know but also understand what is at stake. Otherwise, it’s going to be another Decode saga, the Icelandic story that tells of the turning of private, individual medical data into a commodity, with the destruction of human life as an end.