When Nancy Smith’s younger sister collapsed and died during a game of squash
at the age of 26, it seemed like a terrible but isolated tragedy. That at
least was what the doctors said, and for 12 years Smith and the rest of her
family believed it.
Then in 2003 Smith fell ill. Suffering heart palpitations and breathlessness,
she was admitted to hospital, where tests revealed that she had
car-diomyopathy, a heart disorder renowned for its ability to stalk down the
generations in afflicted families.
“Getting that diagnosis was like the end of my world,” said Smith. “I realised
I could never go back to being the person I had been.”
Smith, now 47, had always prided herself on keeping active but realised that
her lifestyle, far from keeping her fit, had simply hastened the onset of
the disease, which doctors soon realised had almost certainly killed her
sister.
“My biggest thought was: if only we’d known,” she said. “We could have done
something to stop this happening to us. That was when I realised the same
thing could happen to my three children.”
Nancy’s generation is, however, likely to be the last generation of her family
to be left in such ignorance.
It was 55 years ago that James Watson and Francis Crick worked out the
structure of DNA, the molecule that holds the blueprint for life. But it was
not until 2003, the year Nancy was diagnosed, that scientists published the
first transcripts of the human genome.
The human genome is the collective term for the DNA found in almost every cell
in the body. Every bodily function, from memory to sperm or egg formation is
controlled by DNA - so the genome has to hold the code for hundreds of
thousands of different proteins and other molecules needed by the body.
Last week came the publication of Watson’s genome, detailing the six billion
“bases” that make up his DNA sequence. In layman’s terms, it contains a list
of the genes that control his body. The information would fill a stack of
paperback books 200ft high.
It also emerged that about 10 people have paid £170,000 each to become the
first private individuals to have their genomes analysed.
More importantly for Smith, researchers have used similar technology to
pinpoint some of the genes linked to cardiomyop-athy, giving her, her three
children and her sister Cathie a deep insight into their medical destinies.
It was the kind of knowledge many people might shy away from, but when Nancy
offered her teenage children the chance to have their genes tested they took
it. “I saw my sister die, and if I could stop that happening to one of my
children, then I would move heaven and earth,” she said.
Two of her children were given the all-clear, but her eldest son, Robert,
tested positive for the mutated gene. “It was terrible to have it confirmed
but we all felt it was better to know what we were dealing with,” said
Smith.
The publication of Watson’s genome gives us the hope that in the near future,
perhaps within a decade, we may all know what genetic diseases we are
dealing with and how best they should be treated. Scientists hope true
personalised medicine may become a reality.
Until recently the chance of such knowledge as Smith’s family was given has
been available only to those whose families have inherited diseases.
The advent of commercial gene testing has offered the rest of us some insights
into our genetic inheritance - but has found few takers at prices of about
£500 a time. What’s more, all such tests examine just a fraction of our
individual DNA, seeking out the relatively small number of gene variants
known to cause trouble.
The problem, say scientists, is that although we know there must be many more
such genes, we lack the knowledge to track them down. In Smith’s case, for
example, researchers know that many other genes could be linked to her
condition - but the genome is too big to work out where they all are.
The publication of Watson’s genome shows how such problems may be solved, not
just because of the science, impressive though it is, but because of the
cost. By the time the Human Genome Project came to the end of its 13-year
marathon in 2003, it had spent £1.5 billion on a global effort involving
hundreds of researchers and a multitude of laboratories to work out the
“average” human genome.
An individual’s genome, that of Craig Venter, the American scientific
entrepreneur, has been published before, but at a cost also running into
tens of millions of pounds. By contrast, Watson’s genome was completed by
one lab in two months for about £500,000.
“Even that looks expensive now,” said Jonathan Rothberg, the scientist who
founded 454 Life Sciences, the company that analysed Watson’s DNA. “We did
Watson’s genome months ago, but since then the cost has gone down to
£100,000. I’m confident it will have fallen to £1,000 within six years.”
Last week two of Life Science’s rivals, Complete Genomics and BioNanomatrix,
announced plans for the £50 genome, meaning they could sequence an entire
human genome for “less than the price of a nice pair of jeans”.
This would open up the prospect of mapping everybody’s genome, a process that
scientists hope would lead to rapid progress in preventing or curing
diseases.
RESEARCHERS located the first disease-causing gene, the one causing
Huntington’s chorea, a fatal brain condition, in 1983. Since then about
1,400 other disease-causing genes have been found.
However, such “monogenic” conditions that arise from a single gene represent
only about 5% of diseases. In the other 95%, scientists have realised, there
is something far more complex going on. Genes are involved but several
rather than one - and the lifestyle and environment of those afflicted also
play a huge part.
The subtlety of these interplays means that scientists have great trouble
working out which genes affect which diseases. That is the problem that
whole-genome scanning might help to resolve.
Professor Kay Davies, director of the Medical Research Council’s functional
genetics unit, said: “In complex conditions like, say, schizophrenia, the
number of genes and the subtlety of the interactions means we have to
sequence the genomes of thousands of sufferers to work out what is going on.
The idea is to find out how they differ from those without the disease so as
to locate the genes that are to blame.”
At more than £100,000 per individual genome, sequencing on such a scale would
be impossible. At less than £100 it becomes a real possibility.
Researchers at the Wellcome Trust Sanger Institute, in Hinxton,
Cambridgeshire, are targeting one of the biggest killers of all. “Cancer
cells have a genome all of their own,” said Don Powell, a Sanger spokesman.
“Their DNA mutates as the disease develops. In the past we could only study
a few genes but if we can study the whole genome of a cancer cell and
compare it with normal ones we can really see what is happening and
potentially find ways of stopping it.”
Carlos Caldas, professor of cancer medicine at Cambridge University and a
specialist in breast tumours, believes such research will eventually lead to
personalised medicine.
“Soon we will be able to sequence every gene in a cancer cell to work out what
has changed and gone wrong,” he said. “That could allow us to work out which
therapies will work best for each patient.”
Outwardly healthy people could also have their genome analysed and be directed
as to their inherited risk factors and the precautions, such as exercise and
diet, they could take.
The level of complexity in genetic analysis has made researchers such as
Caldas and Davies concerned about the way breakthroughs in genomics are
being exploited by the private sector and offered directly to the public.
There are now at least two dozen firms offering various kinds of gene testing.
Where they differ is in the range of tests on offer. Some, such as DNA
Direct, launched in 2005, are strictly medical, offering diagnostic tests
for individual disorders like haemochromato-sis, or iron overload. They are
targeting people with a family history of such disorders.
Navigenics, launched this month, is targeting the “worried well” with a £1,200
test that probes the bits of the genome known to contain potentially
troublesome variants associated with 18 conditions, such as multiple
sclerosis and lupus.
Others, such as deCODE genetics, an Icelandic firm, and 23andMe from
California, are trying to interest the public in what some have termed
“recreational genomics”, offering insights into ancestry and racial origins
as well as potential medical problems.
What all these firms have in common is that they offer a relatively limited
service, scanning a fraction of a person’s DNA, usually less than 1%, to
hunt out the rogue genes known to be associated with disease.
“We could sequence everyone’s genomes today but we could not link the results
to what we see happening in people,” said Kari Steffanson, chief executive
of deCODE. “Whole genome scanning is definitely coming but it has to be
linked to medical data on disease and body function.”
Recently such companies have found they have an ambitious rival. Knome
(pronounced Know-me), based in Cambridge, Massachusetts, is the first
company to offer commercial whole-genome sequencing. The cost may be an
eyewatering £175,000, but about 10 people have signed up and the first
results could come next month.
“These individuals are pioneering an emerging science with us,” said Knome’s
founder, Professor George Church of Harvard Medical School. “Whole genome
sequencing represents the future of personalised medicine.”
OTHERS are less excited by the prospect of a brave new world of genetic
testing. John Harris, professor of bioethics at the University of Manchester
and a member of the Human Genetics Commission, said: “The utility of genetic
testing and of having your own genetic sequence is being much hyped and we
are very concerned at the way such tests are being sold. The main advice
that comes from all these tests is that we should get lots of exercise and
sleep, avoid being overweight and not drink too much - and we all know that
anyway.”
Mari Baker, president and CEO of Navigenics, believes such views are outdated.
“We recently tested a woman and found she had an elevated risk of colon
cancer,” she said. “When she visited the doctor they found a growth and
removed it. Our test may have saved her life.”
How people will react to the preventative side of such medical breakthroughs
is unknowable. Humans often have a perverse attitude towards risk, as was
shown by a 1980s study of 360,000 Americans by the National Institutes of
Health.
Researchers spent 10 years trying to persuade the subjects to reduce harmful
behaviour but found 65% kept smoking and hardly any would change their
diets, no matter how much information they were given.
Smith found a similar reluctance to heed the warnings in her son Robert, now
23 and at university in Cambridge. “He knows he could have cardiomyopathy in
his genes but he won’t change,” she said. “He still drinks alcohol and lives
a student lifestyle.”
Smith worries about him but says neither regrets the decision to undergo
genetic testing and that they would be keen to undergo whole-genome scans.
“It gave us control,” she said. “It’s better to know the worst and make your
decisions accordingly rather than just stay in ignorance, but there’s no
doubt that some kinds of knowledge are hard to bear.”
Additional reporting: Jasmine Gardner
Can somebody point me to the NIH study referred to in the article on risk behaviours? Thanks
Peter Smyth, Dublin,
A little learning is a dangerous thing. Playing with DNA could spell the end of the human race.
Scientists play with fire, and somewhere in a sterile laboratory, not far enough from here, military scientists are modifying bacterial and viral DNA for their own dubious ends. And possibly ours.
Because sooner or later one of the little killer germs is going to get out.
Mike Poulsen, Reading, Berkshie
This will eventually lead to cures for genetic diseases. The use of advanced gene therapy has long been talked about. It needed the information being developed even now. The diseases such as cystic fibrosis could be eliminated by 'repairing' defective gene combinations. There is a danger of mis-use as well, but, that is true with every advancement. This info could also help in developing organ cloning skills so that organ replacement will no longer have rejection issues - a new organ will merely be grown from stem cells using the individual's own DNA.
Wes, Iowa City, Iowa USA