Full text of DOI:10.1093/embo-reports/kvd038

EMBO
reports
The key is in the genes, or is it…?
With the human genome project completed, the question is ‘What comes next?’
‘It’s in my genes; my genes are guilty, not
me’, yelled the convicted criminal as he
was led from the courtroom. Will judges
in future have to take into account the
genetic makeup of the perpetrator when
deciding the sentence? As information
from various genotyping projects pours
in, the longstanding debate on the bal-
ance between nature and nurture in the
development of phenotypes is being
spiced up. Rapid progress in genome
sequencing and analysis by public and
and cancer. Scientists have already
embarked upon this large and compli-
cated quest by performing genome
surveys on population subgroups, but
much of the legal framework needed to
ensure integrity has yet to be devised. In
the eyes of many, our genes are the last
repository of human privacy, and yet they
are so easily read. It is not surprising,
therefore, that the main theme of the ethi-
cal debate is protection of privacy.
Chairman of Council at the WMA, pre-
sented the WMA guidelines in May this
year at the World Health Organization
headquarters in Geneva. Among the more
important elements in the document is the
requirement that medical databases be
owned by non-profit organizations, but
top of the list is the patient’s right to pri-
vacy of information. The WMA plainly
seeks to pre-empt all eventualities given
the unprecedented scope of distribution
of patient data—a resource that may be of
interest to academic researchers, health
organizations and industry. Indeed, as the
words: ‘…is not intended to criticize any
existing or planned database in any coun-
try’ hint, the WMA might not wholeheart-
edly agree with the approach taken by
some genotyping projects.
Such projects have started springing up
in many areas of high genetic homogen-
eity with good medical and genealogical
records, and at least one, deCODE, is
commercial. The Icelandic company has
frequently been labelled the ugly face of
commercialism, but this is probably a
backfiring of the policy of its chief execu-
tive officer, Kari Stefansson, who has
enthusiastically engaged himself in public
debate. Having developed its ethical
standards in collaboration with the Ice-
landic authorities, and seeking Institu-
tional Review Board approval for all its
projects, deCODE, via a subsidiary, was
recently granted the licence to run the
Icelandic Ministry of Health database.
Furthermore, the decryption key for the
subject identity encryption algorithm is
held by the Icelandic government author-
ities, not by deCODE.
commercial projects is producing
a
mountain of data that will be used to
explain behavioural traits, and develop
new and improved diagnoses and treat-
ments for numerous diseases. But dabble
with others’ genes at your peril; this infor-
mation has serious ethical, financial and
social implications for the individual and
society at large.
Genetic material should not be
thought of as the sole property of
an individual, because it may
hold the key to new diagnoses
and therapies
Protection of patients’ private informa-
tion was enshrined in the Health Informa-
tion Declaration of Geneva in 1948 when
the genetic code and structure of DNA
were still unsolved. Then, a patient was
simply a medical entity. Today, a patient
may be considered a temporary guardian
of a shared genome. Genetic material
should not be thought of as the sole prop-
erty of an individual, because it may, in
conjunction with medical data and family
trees, hold the key to new diagnoses and
therapies that could benefit society. And
since it has also become a potential gold
mine for industry, we may well ask ‘who
owns the human genome?’
Clearly, new conventions must be
established to allow researchers in
academia and industry to use genetic data
without violating the privacy of the
patient. For this, and other reasons, the
World Medical Association wishes to
establish a code of ethical principles for
database operation. Dr Anders Milton,
Our genes are the last repository
of human privacy, and yet they
are so easily read
On July 26th, 2000, President Clinton
announced the publication of the first
map of the human genome: ‘Without a
doubt, this is the most important, most
wondrous map ever produced by human-
kind.’ Knowing ‘the language in which
God created life’ as Clinton put it, scien-
tists and doctors in the field of medical
genetics now have the necessary know-
ledge to enter a completely new era of
medical research, one in which research-
ers will for the first time tackle genetic dis-
eases at their roots. These include some of
the most devastating ailments such as
Alzheimer’s, schizophrenia, Huntington’s
Public genotying projects include the
Northern Swedish Health and Disease
Study, which involves two facilities, one for
sequencing (National Centre for Large Scale
DNA Sequencing: http://www.biochem.
kth.se/GenomeCenter/), the other for dis-
ease gene identification (SSF Genotyping
100 EMBO Reports vol. 1 | no. 2 | 2000
© 2000 European Molecular Biology Organization

analysis
identify genes involved in a particular trait.
This approach, practised on a Finnish
sample group, recently identified a likely
predisposing locus for schizophrenia on
chromosome 7q22 (Ekelund et al., 2000).
However, as witness to the multifactorial
nature of the disease, there is additional
strong evidence for linkage (though not
predisposition) to several other chromo-
some regions including 5q, 6p, 8p, 9, 13q,
18p, 20 and 22q (Karayiorgou and Gogos,
1997).
Centre: http://www.genome.uu.se), both at
Uppsala. The project was begun in 1998,
and will run until 2002. Estonia, another
region of high genetic homogeneity, has
also started a Human Genome Heredity
Project with the aim of producing high den-
sity SNP (single nucleotide polymorphism)
maps from one million subjects between
2001 and 2010 (http://www.genomics.ee/
press.html). Each project has established its
own operating rules in co-operation with
the population and authorities concerned.
By mining information from genetically
closely related individuals with known
family trees these projects seek to corre-
late genotypes with phenotypes, as docu-
mented in a patient’s medical records, to
something freely given by you? Both sce-
narios have recently arisen in the USA.
One involves a diagnostic test developed
from two men who lack a receptor neces-
sary for HIV entry into T cells, and have
therefore remained uninfected despite fre-
quent contact with infected individuals
(Connor et al., 1996a,b). In the other case,
a hospital research institute obtained a
patent on the Canavan disease gene
(responsible for a fatal childhood neuro-
logical disease), which was discovered by
screening Ashkenazi Jews (Kaul et al.,
1993). Should patients write their own
contracts with researchers, covering the
possible patenting of medical advances
developed from their DNA? As a report in
the New York Times
Despite the fact that we can now
identify more predisposing
genes, we must resign ourselves
to the fact that they will never be
the whole story
recently concluded,
it is important that
research subjects do
not feel cheated and
Genes and Society
These and many other issues relating to the sequencing and
analysis of the human genome have been extensively discussed
at the ‘Genes and Society: Impact of New Technologies on
Law, Medicine, and Policy’ conference on May 10–12, in
Cambridge, MA. Information about the conference and its
organisers, the Whitehead Institute, can be found at http://
www.wi.mit.edu/news/n&e/policy2000/home.html.
A joint conference organized by the European Molecular
Biology Laboratory and the European Molecular Biology Organ-
ization will devote one day to human genetics. ‘Science and
Society; Developing a New Dialogue’, takes place from 10–12
November, in Heidelberg, Germany. The organizers invite scien-
tists, social scientists, journalists and policy makers to discuss the
impact of the life sciences on society before a public audience
(http://www.embl-heidelberg.de/Conferences/SciSoc00/). This
represents a rare opportunity for the reporting of a wide-ranging
debate on many aspects of public concern and interest.
embittered, other-
wise they may not
participate in geno-
typing projects that
could benefit many
others.
Although the study
of clinically well-
defined genetic dis-
eases has raised a
far-reaching ethical
As more knowledge about the develop-
ment of diseases, personality and behav-
iour is gathered, it also becomes clear that
environment and life-style play much
larger roles than previously assumed.
Cancer is a prime example; intelligence is
another. A mouse called Doogie, the cre-
ation of Joe Tsien at Princeton University,
recently became smarter than the average
mouse, demonstrating how genes might
influence learning and memory. Sadly,
Doogie, as happens to many stars, was
misrepresented in the media fame-making
machine, demonstrating admirably how,
once played out in the media, an emotive
topic can become more hype than sci-
ence. What Tsien really showed was that
manipulating the expression of a single
gene coding for the subdomain of a
neuroreceptor could increase learning
ability in mice (Tang et al., 1999). The
waters of reality, however, are muddier
than the media wish the public to believe:
shortly thereafter, another study (Crabbe
et al., 1999) showed that genetically iden-
tical mice behave differently under nearly
identical conditions. From this it appears
that even small environmental differences
can have a profound influence on the
development of a trait. So, despite the fact
that we can now identify more predispos-
ing genes than before, we must resign
ourselves to the fact that they will never
be the whole story.
debate,
this
is
nothing compared
with the ideological
quagmire that behav-
ioural
geneticists
wade through when
trying to correlate
genotype with phe-
provide a reliable set of genetic markers
for a variety of diseases. This approach
promises more efficient and accurate
diagnosis, better risk evaluation, and new
or improved treatments, and has therefore
attracted considerable interest from the
pharmaceutical industry.
So imagine you are a patient in a geno-
typing project. You may have gone
through the tribulations of giving consent,
and satisfied yourself that your data are
anonymous and secure, but what if your
DNA proves to be of commercial interest?
Researchers may find a genetic marker for
your inherited condition and decide to pat-
ent it as part of a diagnostic test. Should
you be a beneficiary of the patent, or
should you, indeed, be outraged that
someone is seeking to make money from
notype. Invariably the traits they study are
complex (involving more than one locus),
and are frequently under substantial envi-
ronmental control. In clinical terms, the
hope is that genetics will open the way to
the understanding of psychiatric diseases.
However, at present even the physiological
basis of psychiatric disorders is not well
defined. Because the development of a psy-
chiatric phenotype is a complex process,
traits often lie on a continuum from normal-
ity to clinical significance. Whether a per-
son has a ‘disease’ is often a very subjective
matter.
The latest method for identifying disease
genes is whole genome association. By
scanning genomes for mutant loci that
appear consistently within and between
sets of sibling pairs, scientists expect to
© 2000 European Molecular Biology Organization
EMBO Reports vol. 1 | no. 2 | 2000 101

analysis
Ekelund, J. et al. (2000) Genome-wide scan for
schizophrenia in the Finnish population:
evidence for a locus on chromosome 7q22.
Hum. Mol. Genet., 9, 1049–1057.
Karayiorgou, M. and Gogos, J.A. (1997)
Dissecting the genetic complexity of
schizophrenia. Mol. Psychiatry, 2, 211–223.
Kaul, R., Gao, G.P., Balamurugan, K. and
Matalon, R. (1993) Cloning of the human
aspartoacylase cDNA and a common missense
mutation in Canavan disease. Nature Genet., 5,
118–123.
And so we are building a mountain of
knowledge that at once says much and
little. But how do we communicate this to
the public? People are still in the process
of grasping Mendelian genetics; it is a fur-
ther conceptual step to accept the com-
plex genetics and interplay with the envir-
onment involved in the development of
behavioural traits. While the benefits of
medical genetics are important to
emphasize, we need to be sensitive to the
public’s concern for privacy of data and
integrity of use of those data. Further-
more, we must acknowledge their fear of
the re-emergence of eugenics in the form
of prenatal testing for inherited diseases.
Knowing and analysing the sequence of
the human genome holds great promises
as well as great dangers. Knowledge per
se has no value without a worthy applica-
tion. It is up to us to develop the promises
and thwart the dangers. As Britain’s Prime
Minister, Tony Blair, said in his statement
on the human genome project: ‘With the
power of this discovery comes, of course,
the responsibility to use it wisely.’ Per-
haps what he meant was ‘…must come
the responsibility…’
Connor, R.I., Paxton, W.A., Sheridan, K.E. and
Koup, R.A. (1996a) Macrophages and CD4+
T
lymphocytes from two multiply-exposed,
uninfected individuals resist infection with
primary non-syncytium-inducing isolates of
human immunodeficiency virus type 1. J.
Virol., 70, 8758–8764.
Tang, Y.P., Shimizu, E., Dube, G.R., Rampon, C.,
Kerchner, G.A., Zhuo, M., Liu, G. and Tsien,
J.Z (1999) Genetic enhancement of learning
and memory in mice. Nature, 401, 63–69.
Connor, R.I., Sheridan, K.E., Lai, C., Zhang, L. and
Ho, D.D. (1996b) Characterization of the
functional properties of env genes from long-
term survivors of human immunodeficiency
virus type 1 infection. J. Virol., 70, 5306–5311.
Crabbe, J.C., Wahlsten, D. and Dudek, B.C.
(1999) Genetics of mouse behaviour:
interactions with laboratory environment.
Science, 284, 1670–1672.
Andrew Moore
The author is a contributing editor to EMBO
Reports.
DOI: 10.1093/embo-reports/kvd038
JBIC will pool Japanese genomics research
Japan’s efforts to catch up in bioinformatics
with the USA and Europe in the rapidly
emerging field of bioinformatics.
part of the Japanese economy and poli-
tics. In the field of biotechnology, it had
started half a century earlier with the
establishment of the Japanese Organiza-
tion of Industrial Fermentation in 1942. Its
successor, the Japanese Biotechnology
Association now comprises a group of
300 companies, 100 public organizations
and 1300 academic institutions. Often
under the auspices of MITI, these groups
focus and drive research and develop-
ment further, and have a considerable
influence on Japanese economic politics.
L
ast month, the Japan Biological Inform-
atics Consortium was officially estab-
lished as an independent, non-profit
organization after having reached all of its
planned goals within its first 3 years. JBIC
is a consortium of academia, government
and industry, and its aim is to pool Japan’s
research resources in bioinformatics.
Founded in 1998 by the Japan Biotech-
nology Association (JBA) with financial
support from the Japanese Ministry of
International
‘There has been no infrastructure for bio-
informatics, the interdisciplinary science.
Research activities were not integrated. We
have to join forces,’ Kazuo Katao, director
of the Biochemical Industry Division, Basic
Industries Bureau of the MITI, explains why
the Japanese government decided to pro-
vide funding for the establishment of an
interdisciplinary organization. To close the
gap particularly with the USA, Katao, a
former chemical engineer, created JBIC in
1998 with a phone call. ‘I called JBA to
establish the head of the body to fix the lack
of infrastructure in Japan,’ he recalls. ‘We
don’t have many [management] resources
to invest, so I called on the JBA council,’ he
explains why MITI was asking the Japanese
industry for help.
Trade and Indus-
try (MITI), it will
now
with governmen-
tal institutions
contract
It is Japan’s perception that it has
to catch up with other countries
in genomics research and
bioinformatics
and biotechnol-
ogy companies
to pursue and
support genom-
ics research and
application. JBIC
is part of a grow-
The industrialization of biotechnology
with heavy support from the government
is a legacy of the late Prime Minister
Kenzo Obuchi and falls under 1999’s
‘Millenium Project’. However, the intense
co-operation between industry and
academia has always been an essential
ing
Japanese
Another impetus for the establishment
of JBIC is Japan’s perception that it needs
The father of JBIC,
Kazuo Katao
effort to catch up
102 EMBO Reports vol. 1 | no. 2 | 2000
© 2000 European Molecular Biology Organization