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FOR every dollar that the US spends on mapping the human genome, a few
cents will be set aside to study the ethics of how the information is put
to use. Yet debate over how the project’s results will be used already threatens
to overshadow scientific results in the public’s mind.

Biology’s biggest single undertaking lies largely in the hands of James
Watson, Nobel-prizewinner and co-discoverer of the structure of DNA. Watson
runs the US National Institutes of Health’s Center for Human Genome Research,
the richest outfit in the exploration of the genome with $108 million pledged
to it for the next year. Watson promised last year to allocate 3 per cent
of the centre’s money for research on ethical, social and legal ramifications
of the project. In the light of the attention the subject is getting, he
has increased the ethical budget to about 5 per cent, or about $5 million.
More support will come from the Department of Energy, which is also taking
part in the mapping project.

That may seem a lot to pay for speculation on the problems a map of
the human genome could present. But troubles have already materialised.
The most immediate involves the most common inherited disease in the US,
cystic fibrosis.

Last summer, researchers in the US and Canada located the mutated gene
involved in most cases of cystic fibrosis, an inherited disease that causes
the build-up of mucus in the lungs and digestive system (see ¿ìè¶ÌÊÓƵ,
‘The search for the cystic fibrosis gene’, 21 October 1989). Half the children
born with the disorder die by their early 20s, and most of the remainder
by the age of 30. About one white person in 20 carries one copy of the defective
gene, although children must have two copies, one from each parent, to get
the disease. About one in 2500 newborn babies has cystic fibrosis.

By last December, several biotechnology companies were competing to
introduce a test to screen for people who could pass on the genetic defect.
With as many as 12 million people carrying the defect, the market for testing
in the US could run to several hundred million dollars a year.

Yet the American Society of Human Genetics (ASHG) recently warned against
widespread screening. The society posed several questions still to be answered.
Should the whole population be tested? What is the value of the information
if no treatment exists? What procedures exist for counselling those who
are found to be carriers, or pregnant women whose unborn babies have the
disease? The known genetic mutation accounts for about 75 per cent of the
cases of cystic fibrosis. Some other defects in the gene cause the remainder.
Screening a potential parent with the current test will catch only between
70 and 75 per cent of the carriers. Because both mother and father must
be carriers to pass on this recessive disorder, each must be tested, so
the probability of detecting a couple at risk reduces to about 56 per cent.
‘That’s not high enough,’ says Thomas Caskey, a molecular geneticist and
president of the ASHG. Caskey says that until a more discriminating test
is developed, screening should be offered only to members of families with
a history of the disease.

‘You can’t do anything in genetics that doesn’t raise ethical issues,’
notes Keith Brown, president of GeneScreen, a company in Dallas, Texas,
that offers a test for cystic fibrosis. GeneScreen accepts blood samples
only from doctors and genetic counsellors, says Brown. The company screens
them without inquiring into the patients’ family histories.

Companies such as Brown’s are anticipating new tests for common illnesses,
such as cancer or heart disease, to build their businesses. Brown acknowledges
that such tests could divide people into groups labelled on genetic grounds.
‘But if you can detect a higher risk of breast cancer, a woman could have
mammographies more often. Is that not a better use of our health dollars?’

The debate over screening for cystic fibrosis is an example of the ethical
dilemmas that could dog the genome programme as it generates new information.
Mapping aims to establish markers throughout the 46 chromosomes, after which
molecular biologists will keep improving the resolution and filling in the
gaps. In the meantime, however, the cartographers are tarrying at certain
islands to collect information about genes associated with disease. For
each such gene, a screening test could follow.

Mappers such as Caskey do not need convincing of the task’s value, although
some differ over how to accomplish it. Others are not fully convinced. For
many, the genome project may generate information that could be put to dangerous
uses.

Pitfalls for pioneers

Lee Hood, chairman of the division of biology at the California Institute
of Technology, has pioneered ways to map and sequence the genome. Yet Hood
sees serious ethical pitfalls in the path ahead. ‘Society must set up ways
so that information is kept confidential,’ says Hood. ‘The information belongs
to physicians and individuals – not companies.’

Another concern lies with screening for diseases with no cures. Nancy
Wexler, associate professor at the department of neurology and psychiatry
at Columbia University’s medical centre in New York City, heads a panel
that advises Watson on ethics. Wexler has Huntington’s disease in her family.
She has a 50 per cent chance of carrying the gene that causes fatal illness.
A reliable test for the defect exists, but Wexler has decided not to take
it. ‘When you think of yourself as a carrier (of a trait that has no treatment),
psychologically it has an impact,’ Wexler told a Congressional panel recently.

‘If I knew today that I had the gene and I knock over a glass of water,
which I could easily do, then I am going to sit here and struggle with the
thought, ‘Is this the first symptom?’ instead of thinking about the ethics
committee of the human genome programme,’ she says.

Wexler noted that screening for a defect that causes sickle cell disease,
a recessive, disabling anaemia found mostly among people of African or Mediterranean
origins, boomeranged on scientists attempting a pilot screening project
in Greece. To contract the disease a child must inherit the faulty gene
from both its parents. In the pilot project in Greece, carriers of the trait,
especially women, were stigmatised by the community, even though they were
perfectly healthy. When they came of marrying age, only one group would
consider them eligible – other carriers. In effect, the test raised the
general risk of the disease in the population.

Eugenics is often mentioned in the same breath as the genome programme.
Although Americans practised forms of it in the country’s past – laws mandating
sterilisation of the mentally disabled still exist on paper – few experts
consider it a serious threat. More real, however, is the potential of genetic
mapping to change the way people are employed, promoted or insured. By the
1970s, almost 100 genetic disorders were thought to predispose people to
toxic effects of substances found in the work place and environment. In
1982, a survey of 366 of America’s largest companies found 17 already using
genetic screening when taking on new staff, and 59 intended to begin. British
insurance companies are also ‘interested’ in genetic developments, according
to a small survey carried out by David Cooper of King’s College Hospital
in London and Michael Barefoot of the University of Edinburgh in 1987 (see
¿ìè¶ÌÊÓƵ, ‘Can you buy insurance for your genes?’ 16 July 1987).

Industrial scientists say they need to protect workers who are genetically
susceptible to dangerous substances in the workplace, such as chemicals.
They also might screen for a congenital spinal condition before employing
labourers. Companies also want to protect themselves from lawsuits by workers
who contract diseases or are injured on the job, as well as to reduce time
lost due to disability or illness.

Companies will go to great lengths to screen their workforce. In 1985,
49 per cent of employers in the US required job applicants to take medical
examinations. These ranged from psychological tests to X-rays of the lower
back for construction workers. They included lie detector tests, handwriting
analysis and a broad array of psychological questionnaires that purport
to tell whether a potential employee is honest, mature, well adjusted or
productive. Employers are now testing employees’ urine and sometimes their
hair, looking for signs of drug abuse.

Normally, American companies cannot screen applicants for vulnerability
to some ‘future’ illness. But a court has ruled that a company may reject
a job applicant if it is 90 per cent certain that he or she would have a
heart attack in a particular job. No rules exist for calculating that risk.

An example of the effects of such tests lies with a case in 1969, when
four army recruits with sickle cell trait died while training at high altitude.
The trait affects haemoglobin, which carries oxygen in the blood. Evidence
that some asymptomatic carriers of the trait suffer disabilities is murky,
yet the armed forces have disqualified carriers from some occupations.

Outrage from unions has persuaded many companies to stop genetic testing.
Keeping the tests was not worth a fight because they were not that accurate
anyway. But the new genetics could change that. As Dorothy Nelkin and Laurence
Tancredi point out in their book Dangerous Diagnostics (Basic Books, 1990),
the best defence a company has in occupational lawsuits is a highly accurate
diagnostic test. Companies will be on the lookout for refinements.

Geneticists apparently oppose mandatory screening in the work place.
In the most comprehensive review of ethical attitudes toward genetics yet
undertaken, Dorothy Wertz and John Fletcher surveyed 682 geneticists in
19 countries. They posed several hypothetical situations. One supposed that
a reliable test for alpha-1-antitrypsin deficiency existed (some companies
already test for this trait). Most people with both copies of the defective
gene, known as homozygotes, will develop the lung disease emphysema. Heterozygotes,
those with only one copy of the gene, have lowered levels of alpha-1-antitrypsin
and are believed to be at increased risk if they smoke or work in dusty
environments.

The survey discovered that most geneticists are wary of allowing insurers
and employers to possess such information. In 10 countries, the majority
polled strongly believed that testing workers for alpha-1-antitrypsin deficiency
should be voluntary. Most said it was the worker’s right to decide, while
40 per cent said they feared that workers with the trait might be unfairly
stigmatised. But most of the geneticists polled in East Germany, Turkey,
Brazil, Hungary and India said testing should be mandatory.

Insurers pose another dilemma. In the US, health insurance is a private
arrangement for most people, who obtain it either themselves or through
their employer. Insurers charge higher rates or sometimes deny coverage
for illness or death if a person’s medical history or habits, such as smoking,
suggest a higher risk of disease or death.

‘Insurers have no current interest in ordering such (genetic) tests
themselves,’ says Robert Pokorski, head of medical genetics at the American
Council of Life Insurance. ‘We are approaching testing very cautiously.’
But insurers would like to see the results of tests if doctors already have
them.

The allure of genetic information, in fact, is too great for insurers
to resist. An insurance company stands to lose to its competition if a higher
percentage of its clients file more and larger claims due to earlier deaths
or more frequent illnesses. The incentive is to weed them out, or charge
them higher rates. Pokorski gives the example of a man who is screened for
Huntington’s. If he tests positive, he may buy a very large amount of life
insurance. Frequent claims like these would drive premiums up for the rest
of the company’s customers, since the company’s costs are spread among them.

Ninety per cent of Americans acquire health insurance as part of a large
group and usually are not given medical tests at all. The rest would be
vulnerable to genetic screening, however, as would many people seeking life
insurance.

Several researchers from Harvard University have begun a survey of North
America looking for evidence of genetic discrimination. Paul Billings of
Boston’s New England Deaconess Hospital and his colleagues have already
compiled several cases of discrimination, which, although anecdotal, reveal
some public misunderstanding of genetic disability. Insurers denied people
policies for having the genetic mutation for Charcot-Marie-Tooth disease,
a nonfatal, clinically variable neuromuscular condition. The Harvard researchers
also note that a job was denied to a man who was an unaffected carrier of
Gaucher disease. Furthermore, say Billings and his colleagues, a person
with hereditary haemochromatosis, excessive iron storage, was denied insurance,
even though he had been successfully treated for years and was free of illness.

Building genetic ghettos

Insurers may have a valid economic justification for charging those
at greater risk higher rates. What critics worry about, however, is something
more subtle – a creeping stratification of the population into genetic ghettos.
Most outspoken is the Committee for Responsible Genetics, a group in Boston
with members in science and social science. The council warns of a new status
in society: the ‘healthy ill’. These people might function perfectly well
but, like Jews forced to wear the five-pointed star in Germany before the
Second World War, would bear a stigma labelling them as less than whole.

On a more scientific level, the committee objects to a gene-centred
view of illness. The genome programme, says the council, is ‘reductionist’
because it assumes that genetics can supply a quick fix to physical and
behavioural human failings. Sheldon Krimsky of Tufts University in Massachusetts,
chairman of the council and a philosopher of science, warns of the ‘mystification’
of genetics.

‘One component of an organism is taken out and given special status,
forgetting about the rest of the organism,’ Krimsky says of the new philosophy
of genetics. The result is a ‘hegemony’ of the gene.

Hood and others who are regularly involved in genetic research disagree:
‘The genome project just gives us a very powerful tool to understand how
genes interact with their environment.’ It is, he says, the inverse of what
the Committee for Responsible Genetics is saying. ‘The genome project will
help us get a better handle on how the environment works,’ Wexler adds.
‘For example, the initial agent in an illness may be a gene that then permits
a pathogen to work,’ she argues.

Those in charge of the genome programme have made little progress in
tackling its ethical ramifications. In late 1989, with several million dollars
to spend, the National Institutes of Health called for proposals to study
the subject. According to a scientist involved in reviewing the responses,
they were ‘underwhelming’, and only one is even being considered for support.
The NIH has rewritten its request to be more specific.

Wexler expects ethical, social and legal considerations of the genome
project to continue to grow in importance. Besides grappling with discrimination,
geneticists will also face opponents of anything that raises the demand
for abortion. Most pressing, however, is the need to educate the public.

‘There is not a good base of public understanding of probabilities and
risk to build on,’ says Wexler. ‘The more the public can perceive the benefits
to public health of the genome programme, the more they will see its value.’