2020 – Buying good genes
• Jim Johnson on a perfect future

Forget 2001: a space odyssey, Buck Rogers and any other visions of the 21st century that centre around adventures in space, they got it wrong. Sure we’re sending up the odd satellite into the far reaches of the solar system, but us humans still haven’t got any further than the moon. And as for super intelligent robots with the capability of rebelling against their human creators, we’re not quite there yet either – but apparently Dyson have nearly perfected the first autonomous vacuum cleaner, its just having a little difficulty with corners and doorways. Space and robots are for geeks; the 21st century will really belong to biology.

When Watson and Crick deduced the double helical structure of DNA in the early 1950’s they revealed how genetic information is transmitted through successive generations. Back then, did they realise the future implications of such an important discovery? Scientists now had an understanding of the basic instructions for the building and maintenance of life.

Today we can clone animals and we’re on the verge of cloning humans too. We can chop genes from one species and stick them into another totally different one, and remarkably, end up with a living product not some sludge at the bottom of a test tube. Soon we’ll know all of the three billion bases that make up the human genetic code. So what exactly are we going to do with all that information…?

The human genome is all of the DNA that makes up a person. DNA (Deoxyribonucleic acid) is the molecule that makes up our genes. It is made up of four similar chemicals, known as bases which are abbreviated as A, T, G and C. The order of these bases is vital. It dictates whether an embryo will develop into a human, a fly or any other organism, all of which have their own specific genome. Genes carry information for making all the proteins required by all living organisms. These proteins determine everything about us, how we look, how well our bodies fight infection or metabolise food, and to some extent how we behave. By mapping the human genome scientists have obtained an instruction manual on how to make a person.

The Human Genome Project was launched in October 1990. Its main aim was to sequence the entire human genome. Other targets included identifying the genes that are encoded with this information, developing techniques for analysing this data, and addressing the ethical, legal and social issues that may ensue. Two American agencies, the Department of Energy and the National Institutes of Health jointly produced the original plan that was to be publicly funded. Six years later, however, and a private company, Celera, joined in the effort and the project turned into a race. There was a fear in the scientific community that Celera would patent the information it uncovered, so the public consortium increased its efforts to prevent the genome becoming privatised. In the end both parties announced at the White House on 26th June 2000 that they had each completed a working draft of the genome. By the end of February 2001 this draft had been finalised and both teams published the genome in scientific journals – showing the 30,000 or so genes that it contained.

The Future of Medicine
Information gained from the Human Genome Project will primarily be applied to medicine. We already know quite a lot about genes and disease. It is currently possible to screen for numerous monogenic diseases such as cystic fibrosis, Tay-Sachs and sickle cell anaemia. But most disorders aren’t caused by just one gene but several, so we’ll need to take a different approach to tackle these. Traditional pharmaceutical sciences such as biochemistry will be combined with our new understanding of genes and proteins to develop a new branch of medicine, called Pharmacogenomics.

Pharmacogenomics is the study of how an individual’s genetic profile affects the body’s response to drugs. By 2020 this science will be used to tailor-make drugs for individuals depending on their specific genotype. It will do nothing less than revolutionise medicine. Drugs will be made that can pinpoint proteins and DNA associated with a particular disease, maximising the therapeutic effect of the drug. By directing treatment to specific areas, damage to nearby healthy cells will be minimised. This will be very advantageous for cancer therapy in particular, at the moment treatments like chemotherapy cause serious side effects because it damages both healthy and cancerous tissue. Tumours will be ‘genetically fingerprinted’ so that drugs can be aimed directly at them, so avoiding the usual complications.

By 2020, when we visit the doctors our individual genetic profile will be amongst our medical records. Currently doctors have to prescribe drugs on a trial-and-error basis. Some drugs just don’t work on some people, or worse, can cause allergic reactions. Doctors will soon be able to immediately rule out certain drugs and prescribe what will be most effective for you. This will increase the patient’s well being immensely by reducing the time taken to find effective treatment.

The current method of determining drug dosage is based on a person’s age and weight. This can be highly inaccurate as a guide. People metabolise at rates often unconnected with either of these factors. So again, knowing your genetic profile will save money and time and improve patient care.

Scientists are already aware that certain people may be pre-disposed to contracting certain illnesses. Knowledge of a person’s genetic profile will allow early screening for disease causing genes. Genes don’t always express information; often they lie dormant waiting for triggers to set them off. For example, if someone is identified as a carrier of a gene that can trigger heart disease, they can be advised to eat lower fat foods and exercise more frequently. By 2020 the list of known disease-causing genes will be much longer than it is now, therefore increasing the number of preventable inherited disorders and removing the need for their treatment altogether.

Vaccines are one of most effective ways of fighting disease, like screening they prevent the onset of illness, which is far preferable to treatment. But existing vaccines are not without flaws. Often live viruses are used in a vaccine to create the required antibiotic response needed to obtain immunity. This can sometimes be risky. Viruses can also be hard to store, making them too difficult to manage and too expensive to use in poorer countries, places where vaccines are more important than anywhere else. By 2020 we will be able to vaccinate with pure DNA or RNA. There will be no need to inject whole pathogens but just enough information to trigger an antibiotic response, but with none of the risks of causing infection. These new vaccines will be easier to store than live viral cells and can be made very economical by engineering the vaccine to infer resistance to more than one strain of pathogen at once.

In Britain the NHS is being stretched to its limits because there is a demographic shift towards an older population. Older people generally require more hospital care than the young but at the same time there are less young people working and paying tax to fund this care. New drugs and therapies are very expensive and it is becoming impossible to meet the needs of everyone. This increase in the average age of the population in most developed nations is set to continue, so we need a solution. Pharmacogenomics may just be our great New Hope. Its benefits include: less adverse reactions to drugs, less failed drug trials, quicker drug approval time, less time on medication, less wastage through over-estimated dosage, fewer side effects caused by treatment, earlier detection and prevention.

Information from the human genome will come in useful in many more ways too. Another exciting development will be in the area of gene therapy. With this we will be able to treat, cure or even totally prevent disease by changing the expression of a person’s genes. This field of medicine is currently in its infancy. Knowledge of the human genome should, however, rapidly accelerate its development. By 2020 I believe that germ-line gene therapy will be approved. If gene therapy targets germ-line cells then changes to the recipients DNA will be passed on through to future generations. Germ-line gene therapy is currently outlawed due to the potential hazards associated with such experimentation. Any mistakes that occur during gene therapy of germ-line cells would not only harm the patient but their future offspring. But by 2020 this argument may no longer be valid, scientists will have such complete knowledge of the genome that gene therapy will be a viable and safe solution. In this way we could ensure that deleterious genes are eventually weaned out of the human gene pool forever. Gene therapy works by inserting correcting genetic information into disease causing genes. To do this the natural biology of a virus is utilised. A virus reproduces by inserting its own DNA into a host cell which then incorporates into the DNA of the host, forcing it to replicate more of the virus. Gene therapy would require the removal of the part of viral DNA associated with disease, and the insertion of the treatment DNA. The modified virus could then be used to target cells that require the addition of healthy DNA.

Freedom of genetic information
So far we have discussed only the benefits that knowledge of the human genome will bring us. Unfortunately progress is unlikely to be a totally smooth process. There is a downside to this wonderful new science and by the year 2020 we will be familiar with some of the negative aspects too. A genetic profile of a human can be a very useful thing as we have seen, but like other information in our medical records it is also private and confidential. Who will be allowed access to our test results? Will it stop at the medical profession or will other groups think they have a right to know even more about us than they do already?

Employers will be very tempted to make use of this information if they can. In some cases this may even be justified. It may be in an employee’s best interest if an employer can identify whether he or she would have an allergic reaction, for example, caused by a substance that they would regularly come into contact with during their working day. But will employers start to bully potential recruits into having genetic tests done, or demand to see the results of any previous ones? In 2020 our understanding of which genes code for which trait will throw up a few surprises. It is likely that we will start to see behavioural types linked to various genes. Traits like intelligence, memory, aggression, mental disorder, kindness and sexual orientation may turn out to be linked to a gene or a group of genes. Should employers have access to such information? It some cases probably yes, if aggression and violence turn out to be genetically inherited then surely these people should be stopped from working with children, or in any profession where they would come into contact with vulnerable groups. Just as someone with a violent criminal record can be disqualified from various jobs.

However, the chances are that more than just genes influence behaviour. Genetically identical twins for example, although they may look alike, often have totally different personalities. But some behavioural problems definitely are inherited; for instance there is clear familial linkage of certain mental illnesses. The social consequences in this area are vast. We will be torn between maintaining human rights and wanting to use information in a just and sensible way. What behavioural problems will we define as disorders and which will be personality quirks? Will we demand individuals are ‘treated’ to be cured from ‘disorders’ like criminality and aggression? There are no straightforward answers to these questions and they will require new laws and legislation.

Presently Huntington’s disease testing has been approved by the Genetics and Insurance Committee (GAIC) for use by insurers. But as more and more tests become available will life insurance companies demand more access to results? Tests for Alzheimer’s, ovarian and breast cancer are already being considered. The GAIC has approved the use of five other genetic tests: myotonic dystrophy, familial adenomatous polyposis, multiple endocrine neoplasia and hereditary motor sensory neuropathy, but the Association of British Insurers has recently withdrawn its approval for their use.
Should insurers pick and choose policyholders? Does this contravene the whole ethos of protection by pooling risk so that everyone can afford cover? Then again, car insurers can pick and choose; some offer cheaper premiums by only insuring groups considered to be at lower risk. Why shouldn’t people with a genetic clean bill of health be allowed to benefit from their good fortune?

Towards Homo sapiens subspecies superior
Everything we have considered so far, whether good or bad aspects of the future use of the genome project will have an impact on the issue of human evolution. By 2020 gene testing, screening and germ-line gene therapy could be so effective that we may start to alter the course of our own evolution. It would begin without controversy with the elimination of harmful genes, those that cause some of the diseases mentioned earlier. Towards the end of this decade even, we will know the location of many other traits, but instead of deleting them perhaps couples will want to encourage them. Genes for intelligence, good looks or athleticism, if they exist then can be selected for. Only the rich will be able to use such technology for non-essential aesthetic screening. Rich couples could buy sperms or eggs containing perfect traits and little or no flaws, and designer babies would become a reality.

On the other side of the scale are those born with ‘inferior’ genetic profiles. What will life in 2020 be like for these people (probably most of us)? Employers may not want us and insurers won’t either. If genomic information became widely available we might have to live with the stigma of inferiority. We may even see the creation of two separate human subspecies. At the top end would be a genetic elite which perhaps wouldn’t want to mate with normal mortals and risk having ugly or unhealthy children. ‘Natural’ human beings would start to become less successful in life, being less able to compete with ‘superior’ humans. The evolution of a new species would require reproductive isolation, which up until now hasn’t happened to humans due to our ability to travel all over the planet. But refusal to interbreed by a genetic elite would mimic geographical isolation. While X-men fantasies are not likely, subtler changes like the creation of a new class system and a new subspecies are not quite so far-fetched. Still, I think this is an unlikely scenario. Human desire will tear apart any attempt at artificial separation. History shows us that even in highly regimented societies classes mingle, however forbidden it may be. Animal instincts like lust should help keep the gene pool stirred up.

Genome abuse
All of the consequences considered so far would arise from legitimate if over zealous usage of information gathered from the human genome. But there is the possibility of criminal abuse. The idea of mad renegade scientists working in secret laboratories with plans for global domination is confined to science fiction stories. But there are examples of science being conducted in secrecy. In a recent issue of WIRED there is an account of an anonymous scientist and client who want to attempt human cloning and are not prepared to wait for US laws to lift the ban on such experimentation. The client wishes to clone his son who had died from a disease. He has managed to keep samples of his son’s body tissue alive in storage. The technology exists to take cells from this tissue and inject them into eggs with their nuclei removed. The eggs can then be grown in a surrogate mother and a clone should be born. Some countries have no laws against human cloning so the American client and scientist can legally perform the procedure elsewhere. So if human cloning goes on in a secret scientific underground, will genome research open up more possibilities for radical experimentation outside legal control?

In the same way that genes can be directly targeted to treat disorders, there is no reason why they cannot be targeted to do damage. The Geneva Convention bans biological and chemical warfare, but it still goes on. Iraq has used sulphur mustard (a blistering agent) and a nerve agent in the war with Iran. It publicly threatened the use of chemical weapons in the Gulf War. Many of the coalition forces involved actually expected to encounter biological or chemical weapons and were trained to deal with them. A sick kind of gene therapy could be an ideal biological weapon. It could be used to target very specific groups or even races of people. Although there is only 0.1% variation in the human genome, there are nevertheless tiny differences unique to separate races. Culture itself shapes our genes. For example, in societies where milk drinking is an ancient practice, people have genes that allow them to digest the milk sugar lactose. People whose ancestors were not milk drinkers tend to lack such mutations. Genomic information could be scrutinised to pick out certain genes unique to certain races and then a way of targeting them could be developed. Sadly, there are people who have probably already given this idea some consideration. Let’s hope that this is a theory that is never capable of working in practice.

It is hard to know how many of these predictions are likely or not. The human genome project has opened up totally new options. We have the chance to do so much benefit for the human race, but at the same time expose new areas of risk. It seems almost certain that this technology will move too fast for our conservative society. Hopefully the significant advances in medicine will outweigh all the potential harm, and many of our fears will prove unfounded.

An end to racism?
Could 2020 be an age of enlightenment? In today’s climate where differences in race and religion continue to cause bitter wars and prejudice, this seems a lot to ask. What the genome project has shown us is that more than 99.9% of everyone’s DNA is identical. This means that it is highly possible that two people from entirely different ethnic groups could be genetically closer related than two people from the same race. School children will be taught about the human genome, it will become as crucial to scientific education as the periodic table of elements. As future generations learn of the similarity of the global population, it will be hard for old-fashioned racist views to persist. Historically speaking, we are all Africans; every other genetic variation that has occurred over the world are just slight variations of those found in Africa. Surely by 2020 the whole concept of differences due to race will seem ludicrous.

In the future, as a result of education, fascist groups over the world will hopefully see their membership start to dwindle. Even moderate parties may have to behave differently. William Hague’s ‘foreign land’ speech in March 2001 warned of the dangers of Britain becoming ruled by Europe and invaded by asylum seekers. How would a speech like that go down in 2020? Will ‘playing the race-card’ still be seen as chasing the populist vote? Hopefully in the future it will be less easy to stir up racist hate in this country and elsewhere, when people have an understanding of human similarities and the pointlessness of racial divide. This is perhaps too naïve a point of view, but it is definitely something worth dreaming about.

© JIm Johnson 2001

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