Stephen, The Financial Times is coming out with a series on new treatments by Biotechs. The first article came out on Thursday. It also mentions Bill Gates and Biotechs:
The genetic revolution: Gene is out of the
bottle
THURSDAY OCTOBER 30 1997
Clive Cookson and Daniel Green on the progress and implications of the
genetic revolution
Ten years ago, Bill Gates read a book called Molecular Biology of the Gene
by James Watson, co-discoverer of the structure of DNA. Microsoft's
chairman quickly made sure that a slice of his enormous personal wealth was
invested in biotechnology companies. It has taken the rest of the world rather
longer to work out that genetic research is about to make a profound
difference to our lives. Now, after false alarms and false dawns, the revolution
is gathering pace.
Silicon chips that scan your genes, and devices that change them in your body,
are no longer science fiction. They are in research and development in
university and corporate laboratories in Europe and the US. In the US, 180
clinical trials involving changing patients' genes are under way.
"Genetics research will have the most significant effect on our health since the
microbiology revolutions at the end of the 19th century," says John Bell,
Nuffield Professor of Medicine at Oxford University.
And not only on people's health. Genetic advances will bring challenges to the
conduct of life, from employment practices to insurance and lifestyle. Some
companies, for example, may demand genetic tests before offering people
jobs or insurance cover. Others could offer genetic treatments that promise to,
for example, make children taller.
Genetic knowledge will affect the way people see themselves, although quite
how is not clear. We may take a more fatalistic attitude to life, blaming
everything on our genes. Or we may, on the contrary, become aware of the
limits to "genetic predetermination" and see how much freedom of action we
have.
This explosion of genetic research is being fuelled by thousands of scientists
spending billions of dollars of public and private money in hundreds of
laboratories around the world. Their endeavour, known as the Human
Genome Project, is by far the biggest research effort in the history of biology.
Its aim is to work out the structure and sequence of the genome: the DNA that
provides the blueprint for a human being. The loosely co-ordinated
international project was launched in 1990 with a target date for completion of
2005. Unlike most big science projects, it is running more or less on schedule
- partly because the private sector's involvement has been much greater than
originally expected. By 2005 any scientist will be able to read the complete
sequence of 3bn chemical "letters" in the human genome, including an
estimated 80,000 genes, the basic units of heredity.
Doctors and patients will not have to wait that long, however, before genetics
makes a difference. Already several thousand genes are known precisely and
partial information is available on many thousands more. Once the sequence of
a gene is known, a scientist can usually work out what it does, because the
genetic code translates DNA into a protein - the type of molecule that does all
the work in the body, from building muscles to carrying messages between
brain cells.
Knowing how individual genes work, however, is just the start of genomics
and perhaps the sole part of the enterprise that is beyond controversy.
Relatively few people suffer from diseases arising from a single faulty gene,
such as cystic fibrosis (CF) and Huntington's chorea.
To bring genomic discoveries into the medical mainstream and tackle the vast
majority of diseases, scientists will have to find out how large numbers of
genes work together with environmental factors to cause the most common
intractable diseases of modern society: cancer, heart disease, auto-immune
diseases such as arthritis, diabetes and Crohn's, mental illness and
degenerative brain diseases such as Alzheimer's.
The genetic component in these complex chronic diseases varies but it seems
often to be between one-third and two-thirds of the cause. The other part
comes from a variety of other factors including diet, infection - and sheer bad
luck.
The practical application of this kind of knowledge falls into three categories:
diagnosis, treatment and prevention.
Diagnosis
Some diagnostic tests are available now, and hint at what is likely to be
developed over the next few years.
In the UK, for example, the only ones on sale identify carriers of the CF gene;
they are supplied by two private companies, University Diagnostics of London
and Leeds Antenatal Screening Service, at a cost of about œ100 each. The
tests are intended mainly for couples planning to have children. If both parents
are positive, each child has a 25 per cent chance of being born with the
disease; they can follow up with an ante-natal test.
Tests of this sort identify "recessive disorders", in which the disease develops
only when a mutation in a single gene is inherited from both parents. They are
the least controversial type, because a carrier of one defective gene will not
become ill. Even here, however, there may be an adverse psychological effect
- and potential implications for insurance and employment, both for the
individual being tested and their family.
Genetic tests that predict the future health of an individual are more
problematic. These include tests for relatively rare diseases, with a single
mutation as a cause; examples range from Huntington's, a devastating brain
disorder, to inherited high cholesterol levels.
But the most important type of predictive test looks for mutations - or
collections of mutations - that predispose people to develop common diseases
such as cancer, Alzheimer's or heart disease. Early examples of these are
already available, for example, to test women for susceptibility to breast
cancer.
It may seem perverse to take a genetic test when there is no guarantee of
contracting the disease nor an effective treatment. But for people with a
known family history of inherited disease, the knowledge itself may be useful,
says Theresa Marteau, director of the psychology and genetics group at
London's United Medical and Dental Schools. A negative result obviously
brings relief, but a study of people with a 50 per cent risk of getting
Huntington's disease showed that even a positive test could lower stress levels
by reducing uncertainty.
The benefits of testing are clearer when there is something you can do about a
positive result. If a young woman has genetic susceptibility to breast cancer,
she can undergo more frequent screening to detect signs of cancer at an early
stage when it is likely to be cured - or she may take the more extreme step of
having preventive surgery to remove her breasts before cancer appears.
On the other hand, it would be pointless - though technically feasible - to take
a test today for genetic susceptibility to Alzheimer's disease. In the first place,
the inheritance patterns and causation for this form of dementia are not clear
enough for people to know from their family history that they are at high risk.
And, more importantly, there is no known preventive action to reduce the
chance of the disease developing.
The big pharmaceutical and diagnostics companies are so far avoiding the
controversial field of testing for diseases yet to be contracted. They are
concentrating research on genetic tests to discover what type of disease the
patient has, once symptoms have appeared, so that the most appropriate drug
may be prescribed. This field, known as pharmacogenomics, should improve
the treatment of many diseases, from cancers to diabetes.
Already, "gene-chips" are on sale. These are made of silicon, like computer
chips, but as well as the electrical circuits they have fragments of DNA on
them to detect mutations in a gene. A computer provides a read-out when a
mutation is detected. Affymetrix, a Californian company, is already supplying
or working on chips to test for mutations in the BRCA1 and BRCA2 cancer
genes, another cancer gene called p53, and in HIV, the virus that causes Aids.
Treatment
Dozens of biotechnology companies are developing ways of changing genes -
gene therapy - with 180 clinical trials already authorised by the US Food and
Drug Administration. The problem they face is how to get the gene, in the
shape of a specific piece of DNA identified through the Human Genome
Project, into the body's cells in such a way that it produces a protein. Trials so
far have not been very successful, but confidence is high.
"I am convinced that the obstacles facing gene therapy are only technical and
will be overcome," says Ed Scolnick, head of research and development at
Merck, the largest US drugs company.
Prevention
Current trials are designed to change the genes in only a few cells, such as the
lung cells in a CF sufferer. More dramatic is the possibility that sperm and egg
cell genes could be changed, which would affect every cell in the body of
anyone descended from those cells.
Such "germ-line" therapy could prevent diseases but also open the way for
abuses such as parents "designing" their children. So far, scientists, ethical
bodies and governments have lined up to condemn the idea, although critics of
gene therapy argue that new genes targeted at ordinary cells could accidentally
find their way into germ cells.
The consequences of genomics are already upon us. They present
opportunities for unprecedented medical advances. And that will be only the
start.
It is likely that changes over the next decade as a consequence of genetic
knowledge will affect our lives as directly as has the information technology
revolution in the past 10 years.
This is the first in a series on genetics. Later articles will look at the
science involved, the commercial aspects and the ethical and policy
issues raised. |
