GENOME PROJECT AND ITS
ETHICAL, LEGAL AND SOCIAL IMPLICATIONS
Science and Technology Division
26 July 2000
TABLE OF CONTENTS
A. The Science of the Human
1. Genes and
2. Genes and
B. The Human Genome Project
C. Related Projects
Protein Structure Initiative
Human Epigenome Consortium
3. The Human Genome Diversity
Ethical, Legal and Social Implications of the Human Genome Project
1. The Existence of Genetic
Ownership and Commercialization
Genetic Treatment of Disease
THE HUMAN GENOME
PROJECT AND ITS
ETHICAL, LEGAL AND SOCIAL IMPLICATIONS
On 26 June 2000, the President
of the United States, Bill Clinton, and the British Prime Minister, Tony
Blair, announced the completion of the first stage of the sequencing of
the human genome, the result of both private and public enterprises. The
human genome has been described as the blueprint from which humans are
derived. Knowledge of this blueprint is widely touted as the first step
toward the prevention, diagnosis, and treatment of disease, as well as
its cure.(1) While some have called the announcement
"hype,"(2) others suggest that
knowledge of the human genome will have an unpredictable impact on medical
science and that the full meaning of the Human Genome Project (HGP) has
been underestimated.(3) Still others have suggested that the most important impact
will be on how we view others and ourselves.(4)
At this time, the outcome
of the Human Genome Project is unknown. Where knowledge of the human genome
takes us will be guided by how we choose to use the information. In making
this choice it is essential that the possible ethical, legal and social
outcomes be discussed as fully as possible, in order that lawmakers may
reach a well-informed consensus.(5) The
following paper is a discussion of the Human Genome Project and some of
the ethical, legal and social implications of knowledge of the human genome.
The Science of the Human Genome
1. Genes and
The genome is the complete
set of molecular information that encodes the instructions for making
an organism. In most organisms (except some viruses) the genome is made
up of deoxyribonucleic acid (DNA). The properties of DNA allow for the
encoding of the information necessary for producing a set of proteins
that defines the physiology and structure of the cells and organs that
make up an organism and provides the basis for passing on this information
to the next generation. In humans, each cell, not including reproductive
cells, has two copies of the complete genome, one inherited from each
Four different kinds of
smaller molecules, referred to as nucleotides and represented by the letters
G, T, C and A,(6) when joined together in a strand make up the larger DNA
molecule. Most DNA occurs as two DNA strands that wrap around each other
to resemble a twisted ladder, whose rungs are formed by the interaction
of complementary nucleotides, A always matching with T and C with G. The
human genome consists of approximately 3 billion of these nucleotide pairings,
often referred to as base-pairs, in reference to the portion of the nucleotides
In forming proteins, the
DNA molecule is decoded as a series of three letter words called codons.
Each codon is associated with one of the amino acids, which are the building
blocks of proteins. The four letters can make up 64 different three-letter
words, while there are only about twenty amino acids; therefore, most
amino acids have more than one codon. The series of nucleotides that contains
the information associated with all the amino acids for a particular protein
is called a gene; however, not all DNA encodes genes. In fact, only about
5% of the human genome is thought to encode information for proteins and
the function of much of the remaining 95% remains unknown. The number
of genes in the human genome is estimated at anywhere between 30,000 and
The making of a protein
involves two steps. In the first, the DNA ladder is "unzipped."
One side of the DNA molecule, known as the template strand, is then used
for the formation of a messenger molecule consisting of ribonucleic acid
(RNA) molecules that are strictly complementary to the DNA nucleotides.
Amino acids then bind to this RNA message in the order dictated by the
position of the respective three-letter codon. It is the order of amino
acids in a protein that determines what the function of the protein will
be; for example, a structural component of a cell, or an enzyme involved
in metabolism. The gene does not strictly govern the final order of amino
acids in a protein, as both the RNA messenger and the protein itself can
be modified independently. Since each cell has the complete set of genes
to make an organism, the specific nature of a cell is determined by the
degree to which each gene is turned on and the degree to which the RNA
and protein are subsequently modified.
The strictly complementary
nature of the nucleotides of the DNA molecule also provides the means
by which genetic information is passed from one generation to another.
Before a new cell is formed, the DNA ladder is split and respective complementary
nucleotides are added to form two molecules of DNA, identical to the first,
yielding a cell with four copies of the complete genome. Shortly after
this stage, the DNA is contained within the 23 pairs of microscopically
visible structures known as chromosomes, after which it separates into
two; the cell divides to yield two identical cells, each with two copies
of the genome. In sexual reproduction an additional cell division occurs,
without a DNA duplication step, so that the resulting cells, either egg
or sperm, have only a single copy of the genome. The fusion of an egg
and a sperm once again produces a cell with two copies of the genome,
one from each parent.
2. Genes and
Approximately 5,000 human
diseases are currently thought to have some genetic component. Some of
the fundamental causes are easy to identify. In the case of Down syndrome
for instance, there is an extra copy of chromosome 21, which is visible
under the light microscope. Other genetic diseases that are strongly under
the control of a single gene have also been relatively easy to identify.
In the case of sickle cell anaemia (SCA), a change in a single nucleotide
of one gene alters a codon so that a different amino acid is incorporated
into haemoglobin, the protein responsible for carrying oxygen in the blood.
Such a change, which is called a single nucleotide polymorphism (SNP),
may cause a change in an amino acid that can have a range of effects depending
on where the amino acid is located in the protein and the change in amino
acid. An SNP can also occur without changing the amino acid because many
amino acids have more than one codon. In Huntingtons disease, another
disease that is strongly determined by genetics, a single gene has a series
of nucleotides repeated many times.
In the case of SCA the gene
is known as "recessive" because it requires two copies of the
gene, one from each parent, to produce the disease in the offspring. If
one parent donates the gene for the disease and the other does not, the
child will not get the disease.(7) In
the case of Huntingtons, the gene is "dominant"; that
is, if one parent has the gene, then half of his or/her sperm eggs will
carry the disease and a child who receives the gene will get the disease.
Thus, a child whose parent has Huntingtons has a 50% chance of getting
As a result of strong single
gene control over some diseases, close to 1,000 genes for a variety of
diseases have been identified and localized to a chromosome through inheritance
patterns. The genes involved in other diseases with some genetic component,
such as cancer, heart disease and mental illness, are more difficult to
identify because they involve multiple genes that are also heavily influenced
by environmental factors.(8) Environment
is only one of many factors that control the degree to which harmful changes
in a gene, or combination of genes, may cause health problems. Potentially
harmful changes in genes may not result in problems if:
environmental factors do not turn these genes on;
only a partial set of the combination of genes underlying a disease;
or genes are not expressed strongly;
leads to only a mild form of the disease;
is recessive and only one copy is present;
damage does not result from environmental substances or ageing.(9)
The extent to which health
problems result from potentially harmful changes to genes is therefore
very difficult to predict. At one extreme, we know that diseases such
as Huntingtons and SCA are strongly determined by changes in a single
gene. As more genes become involved and environmental factors come into
play, the genetic disposition to a disease becomes less and less obvious,
however. Diseases that are heavily influenced by environmental factors
and interaction with other genes are likely to be far more common than
diseases with very strong genetic components. Even strongly deterministic
genes, such as those for Huntingtons, have a range of effects; for
example, some people with the Huntingtons gene live much longer
The Human Genome Project
The Human Genome Project
(HGP) is an international effort, coordinated by the United States Department
of Energy and National Institutes of Health, that aims to determine the
sequence of every nucleotide in the human genome and to identify all the
genes contained within the genome. Formally started in 1990, the project
was intended to complete the working reference genome by 2005 but technical
advances have decreased the timeframe to 13 years.
The genome itself, at six
billion nucleotides long, is far too big to sequence as a whole. The initial
approach was to break it into pieces, determine the order of the pieces,
and then to determine the nucleotide sequence for each piece. A private
company split from the public project, however, and began sequencing DNA
segments in order to patent them. This forced the HGP to change its approach
to match that of the private company and to provide the nucleotide sequence
of the pieces before knowing the order of the pieces.(11)
The statement by President Clinton and Prime Minister Blair 26 June 2000
announced not only the virtual completion of the sequencing of the pieces,
but also a truce between the private and public projects. To obtain a
reference copy of the human genome that is 99.99% accurate, and with all
the pieces in order, will take another three or so years. Various groups
around the world have been working on individual chromosomes and the sequencing
of these is at different stages of completion. Chromosome 21, with the
exception of three gaps 30,000 nucleotides in length, has already been
completed to the final standard.(12) Because this chromosome is implicated
in Down syndrome, some researchers had begun to sequence it before the
start of the Human Genome Project.
Unlike some other countries,
such as Great Britain and Japan, Canada has had no formal national human
genome program and for this reason was not included in the announcement
as a partner. Despite this, Canadian scientists have contributed to the
HGP, for example through the sequencing of genes and ethics studies.(13)
The Government of Canada has contributed to this research; in the year
2000 budget, Genome Canada was allotted $160 million for five centres
of genome science research in Canada.
One of the most significant
aspects of the HGP is that it reverses the way in which science is normally
done. Usually, researchers approach a specific problem and then try to
find its causes, among which might be the DNA sequence of a gene or genes.
The HGP will yield the order of the nucleotides in the human genome, and
identify putative genes, but will not identify their functions. It will
take many years, if not decades, before the gene products are identified
and many more years to understand how they interact with each other and
the environment in developmental, biochemical and physiological processes.
The HGP has also involved
the determination of the nucleotide sequence for the genomes of other
organisms, many of which have been used as laboratory models and so have
many well understood biochemical pathways and physiologies. Since their
genomes have many similarities to the human genome, knowing their sequences
will help to identify genes and the function of genes in the human genome.
C. Related Projects
Protein Structure Initiative
One of the ways to understand
the functions of genes is to understand the structure of the proteins
they produce. This form of study, which is referred to as structural genomics,
is a huge undertaking. Current technology requires weeks and can cost
tens of thousands of dollars to determine a single structure. Moreover,
only a limited number of proteins can be examined in this way; many proteins,
such as those embedded in membranes, are very difficult if not impossible
to crystallize, a process necessary for the protein analysis technique
of x-ray crystallography. Consequently there will be important information
gaps, since many membrane-bound proteins are those targeted by drugs.
While there may be approximately 100,000 genes, there are likely several
hundred thousand proteins, the result of messenger RNA and protein modification.
Including plants and microorganisms, there are millions of different proteins.
The National Institutes of Health is starting a Protein Structure Initiative
that aims to understand protein structural families, structural folds,
and the relation of structure and function. Various private concerns are
attempting to do the same, concentrating on what they feel are medically
Human Epigenome Consortium
In addition to knowing the
genome products, it is also necessary to know when and in what tissues
the genes are switched on. One of the ways hypothesized is through the
addition of a methyl group to cytidine (the C nucleotide). A consortium
consisting of the Sanger Centre in the U.K., the Max Plank Institute for
Molecular Genetics in Berlin, Germany, and a company called Epigenomics,
is initiating a study that aims to identify every methylation site within
the human genome. This could prove to be a project as large as the HGP
3. The Human Genome Diversity
The Human Genome Diversity
Project is still in its planning stages but its goal is to understand
the diversity and unity of the entire human species. The information should
be useful in understanding human biological history, the biological relationships
among different human groups, and the causes and treatments of particular
human diseases. Currently, individual scientists carry on such research
but no samples of human tissue have yet been taken under the auspices
of the North American Committee of the HGDP, and will not be until the
program is more fully planned and ethical guarantees are in place.(16)
Ethical, Legal and Social Implications of the Human Genome Project
From the beginning, it has
been understood that the Human Genome Project will have profound ethical,
legal and social (ELS) implications; thus, between 3 and 5% of its budget
has been devoted to the study of ELS issues. Ethical issues are generally
defined as those raising questions concerning what is moral or right.
Legal issues are those concerning the protections that laws or regulations
should provide. Social issues are concerned with how events may affect
society as a whole and individuals in society.(17)
Clearly, these aspects of the HGP and its possible outcomes are not independent
of each other.
Many of the ELS implications
are not new. The gene for Huntingtons disease was discovered in
1993, after a ten-year search following the localization of the gene to
chromosome 4 in 1983. A test for the disease was developed soon after.
Many of the questions currently being addressed by the ELS issues program
of the HGP have, therefore, been familiar for many years to families afflicted
with Huntingtons. As a result of the HGP, however, society as a
whole will have to deal much more frequently with issues arising from
knowledge of the human genome. Moreover, the implications may be less
clear in the case of genes identified for diseases that have strong environmental
aspects and involve interaction with many other genes.
1. The Existence of Genetic
The existence of genetic
information with respect to individuals and the human population as a
whole will have a profound impact on our day-to-day lives and may well
change how we regard ourselves and one another.
The knowledge of predisposition
to a certain disease and the ability to design "tailor made"
therapies may greatly help in the treatment of disease. Already a company
in Great Britain has applied for a patent on a device that can apparently
detect different forms of over 2,500 genes said to be associated with
traits including behaviour and intelligence.(18)
It has been argued, however,
that it is not proper, particularly at this juncture in history, to search
for such knowledge. For example, some have pointed out that science has
often been co-opted as a tool to accentuate racial differences and to
defend racist practices. Given that humans are far from resolving issues
of race, it is thought that information from the HGP, and such follow-up
projects as the Human Genome Diversity Project, may have the potential
to inflame racism in an already overly racist world.(19)
Equally, some feel that
if the goal of the HGP is to prevent disability and disease, increase
life spans, decrease infant mortality, and increase intelligence, the
money would be far better spent elsewhere.(20) Given that we already know that environmental and social
factors can influence such diseases as diabetes in aboriginal populations
and drug addiction among the socially marginalized, some consider it unconscionable
to dispense limited resources looking for genetic causes for these diseases.(21)
The legal aspects of knowledge
of the human genome are enormous. Already DNA evidence is being used as
a powerful legal tool, particularly in exonerating wrongly accused individuals.
Does this mean that the criminal system should be able to keep a bank
of DNA information on anyone accused and/or convicted of a crime? Could
the database be used for other purposes than simply identifying and eliminating
suspects? A DNA database could contain much more information on individuals,
both guilty and innocent, than does the current system of taking fingerprints.
On a more hypothetical note,
should genes leading to a propensity for criminal activity be found, could
they be used as prosecution or defence evidence in a trial? For instance,
is a suspect who knows that he or she has a genetic disposition toward
criminal behaviour and does nothing to avoid provoking such behaviour,
guilty of a more serious crime than a suspect who is ignorant of having
such a propensity? On the other hand, could genetic disposition be used
as a defence on the grounds that the crime was really the fault of the
gene, not the person?
When a patient tests positive
for a gene linked to risk of disease, does the physician (or the patient)
have a legal responsibility to inform the patients relatives of
their own risks? Suppose a patient finds out that she has a genetic propensity
for breast cancer, but neither she nor her doctor informs her relatives;
would a relative who later developed that form of cancer be able to sue,
on the grounds that the genetic information had not been disclosed?
Ensuring that the judge
and jury in a trial are sufficiently educated to deal with these issues
is yet another problem with which the legal system will have to deal.
On a larger social scale,
knowledge of the human genome could be used to emphasize the similarities
among all humans. The genetic differences between people within an identified
group have already been shown to be greater than the differences between
groups. In other words, people within an "ethnic" population
are more different from each other than the group as a whole is different
from other "ethnic" groups.(22)
This fact is unlikely, however, to deter those who wish to emphasize any
ethnic differences that may be found.
On a more individual level,
the results of the HGP might encourage people to view themselves as being
wholly under the control of their genes. What has traditionally been viewed
as the human spirit might in future be seen as limited by pre-programming
at birth. Thus, though we cannot predict exactly how knowledge of the
human genome will affect society, it could clearly have important consequences.(23)
Individual decisions, such
as choices with respect to mates and reproduction, could also be influenced
by knowledge of genetic makeup. Awareness of personal genetic differences
from a perceived norm might lead to confusion and uncertainty about the
potential for disease, particularly in the absence of adequate professional
consultation. Genetic analysis might reveal a myriad of genetic flaws
that may or may not lead to disease, depending on what they are and how
they interact with the environment. How will individuals select from a
debilitating array of lifestyle choices, none of which has a certain outcome?
Again, analysis of ones own genetic makeup could reveal the genetic
makeup of parents and siblings, including, for example, unsuspected information
about paternity. How willing would people be to share this knowledge and,
if they decided to withhold it, how would they be affected by living with
Ownership and Commercialization
On 11 November 1997, UNESCO
passed its Universal Declaration on the Human Genome and Human Rights.
Article 4 of the Declaration states that "The human genome in its
natural state shall not give rise to financial gains." In most countries,
however, DNA, when isolated from an individual, is not considered to be
in its natural state and therefore can give rise to financial gain. One
of the benefits of the HGP and genomics research in general is expected
to be a thriving biotechnology industry with the potential, in the United
States, to be worth $45 billion (U.S) by 2009. In most technological
industries, innovation has been encouraged through the granting of patents
Researchers who devise an
invention that is useful, new, and unobvious are given approximately 20-year
proprietary rights over its use. To be patentable, discoveries must involve
some human intervention and inventiveness.(24) In return for these rights, the inventor
must make the invention public so that others may, at a price, use it
to further their research.
For approximately 20 years,
sequences of DNA that correspond to human genes have been claimed in patents.
Conceptually, the string of DNA molecules is considered no different from
other chemicals isolated from living organisms, such as penicillin, as
long as it passes the tests for patentability (being new, useful, and
For a number of reasons,
some believe that human gene sequences should never be patentable. A fundamental,
philosophical reason is the belief that the human genome, as an intrinsic
part of every person, is a common heritage that all humans should share.
This line of reasoning has led the Parliamentary Assembly of the Council
of Europe to recommend that European Union countries renegotiate the agreed
Directive that allows the patenting of human genes that are isolated from
the body and applicable to industry, and specifically prohibit the patenting
of human genes.(25)
The World Trade Organizations
Trade Related Aspects of Intellectual Property Agreement includes some
discussion on what member countries can exclude from patentability. Article
27(2) states that anything that is necessary to protect the "ordre
public or morality" can be excluded, as long as the exemption
is not made simply because it is prohibited by law. Section 27(3)(a) states
that member countries may also exclude diagnostic, therapeutic and surgical
methods for humans and animals. No specific clause would seem to prevent
a member country from excluding the patentability of human genes. Canadas
Patent Act does not have an "ordre public" clause.
Some offer logistical reasons
to explain why patents should not be extended to DNA sequences. They suggest
that such patents, particularly on partial gene sequences, would inhibit
innovation rather than encourage it, as the patent system is supposed
to do. This could arise in a scenario, dubbed the "tragedy of the
anticommons," in which numerous people and organizations held patents
on different DNA sequences governing an overall biochemical pathway that
could be the target for a medical treatment. To research that treatment,
someone would have to negotiate for the rights to all the DNA sequences
from all the respective owners; this might be so costly and onerous as
to make further research unlikely. Pure researchers, who would not have
the money, the time or the expertise for a complex series of transactions,
would be the most severely affected. Others, however, refute this argument,
citing the case of the computer industry. Patents on the various parts
of computers certainly do not seem to have impeded the growth of that
industry, though some might say that it has impeded innovation. Others
point out that in the computer industry, the free flow of information
has been a driving force behind such innovations as the GNU-Linux operating
It has also been suggested
that DNA does not pass the tests for patentability on the ground that,
since DNA exists in nature, knowledge of it is simply a discovery, not
an invention. Therefore, while drugs should be patentable, the DNA sequence
upstream from the target of the drug should not be.(27) Moreover, it is said that many of the
techniques used to isolate and manipulate DNA are now routine, and therefore
the inventions are too obvious to be patentable.
In North America, the focus
is more on what level of utility must be shown in order for genes to be
patented, rather than on whether they are patentable at all. The Canadian
Patent Act, as it is written, has for a long time been interpreted
as meaning that genes are patentable material. A problem has arisen because
many private companies have concentrated on sequencing genes in the hope
of obtaining patents on a gene that may one day prove to be useful. Most
of the genes sequenced by the HGP and private enterprises have as yet
unknown functions; thus, applications are being made for DNA sequences
that have no genuine utility. Since the sequences do encode a protein,
some companies have gone so far as to claim that, at a minimum, the protein
could be used for animal feed or in a molecular biological technique as
a DNA probe. In one well known case in the United States, the company
Human Genome Sciences obtained a patent on a gene that was subsequently
discovered by a different researcher to be an entry portal through which
the AIDS virus infects cells. Any future treatment of these cells that
alters this entry portal will require royalties to be paid to Human Genome
Sciences.(28) While the Canadian Patent
Act is similar to its U.S. equivalent, Canadian patenting procedures
are generally more stringent with respect to the utility of the invention
than are those in the United States, the country where the controversy
is greatest. The U.S. Patent Office has recently announced that it will
increase the stringency of the utility requirement for patenting DNA sequences.
Searching for medically
useful, and therefore potentially profitable, genes also raises many ethical
questions. Heritable disease patterns sometimes emerge in populations
that have not mixed extensively with other populations; as a result, private
companies are doing genetic exploration in such relatively isolated areas
as Newfoundland, Iceland and certain tropical islands. In Iceland, a company
called deCODE has been given the rights to produce a health sector database
that will include genealogical, environmental, and molecular genetic information,
along with the combined anonymized patient records of the country. In
Newfoundland, political leaders are apparently coming to the conclusion
that Newfoundlanders should maintain control over their unique genome.(29)
How to regulate the gene hunters without scaring off investment is a familiar
problem to governments that already have experience with charging royalties
and regulating natural resource operations. Gene "mining" companies,
however, present a much more complex and emotional set of ethical issues
than does the natural resources sector.
Genetic Treatment of Disease
From the outset, one of
the defining goals of the HGP has been its potential for molecular medicine.
The concept is that, once the functions of genes are known and we understand
the effects of malfunctioning genes, we will be able to correct the problem
either through the use of designer drugs or by replacing the faulty gene.
It is the latter option that has created the most controversy.
There are two routes to
replacing a faulty gene. The first route, germ line therapy, has the goal
of replacing a harmful gene in a fertilized human egg with a properly
functioning gene that would be passed on to future generations. The other
route, somatic gene therapy, aims to replace the gene in target organs
or tissues of an adult, so as to fix the symptoms in that individual but
not in the next generation. Germ line therapy has the more profound ethical,
legal and social implications.
As yet germ-line therapy
in humans is not possible and some have argued that it will continue to
be so for the foreseeable future. While this kind of therapy may be a
long way off, it would bring, on the one hand, the hope of eradicating
some genetic diseases but, on the other hand, the spectre of eugenics.
The eradication of disease
through germ-line therapy might not seem, by itself, to raise many ethical
questions. After all, humans have eradicated the smallpox virus from the
world, why not diseases with genetic components? Do doctors not have the
moral obligation to provide the very best treatment to their patients
and would not the eradication of the disease be more cost effective in
the long run than continually treating adults with somatic gene therapy?
The main ethical problem arises in defining a "treatable" disease.
Some might say that eradication
of a genetic disease for which there is no treatment and which is always
fatal, should be pursued with all means possible. Others say that this
would be the start of a slippery slope moving on toward the treatment
of less obvious diseases and then to genetic enhancement. Some argue that
if the technology is advanced in order to eradicate some diseases, it
will inevitably be used by parents wishing to "enhance" their
children, giving them the genes for raven black hair and blue eyes or
athletic prowess. It was serious ethical concerns about genetic enhancement
that prompted the Council of Europe to adopt the Convention for the Protection
of Human Rights and Dignity of the Human Being with Regard to the Application
of Biology and Medicine: Convention on Human Rights and Biomedicine. Article
13 of the Convention states that "an intervention seeking to modify
the human genome may only be undertaken for preventive, diagnostic or
therapeutic purposes and only if its aim is not to introduce any modification
in the genome of any descendants." Article 11 of the UNESCO
Universal Declaration on the Human Genome and Human Rights states that
"practices which are contrary to human dignity, such as reproductive
cloning of human beings, shall not be permitted." It is left to individual
states, however, to define exactly what they believe these practices to
be. Thus, while some countries, such as the signatories to the European
Convention, may prohibit germ-line therapy, others may not. It is the
existence of national differences in regulation of research on human embryos
that has allowed controversial research to be performed, for example,
in Singapore. Regulation has thus slowed down the progress of research
but not prevented it.(30)
Another ethical consideration
with respect to germ-line therapy is defining what is normal, what is
a disability, and what is a disease. Which of the genetic variations within
a population ought to be eradicated, if any? In trying to eradicate a
certain variation, are we demeaning those in the population who currently
carry the gene?
Somatic gene therapy has
its own, less controversial, set of ELS implications. These may be less
ominous than eugenics but are of perhaps more immediate concern, given
the more advanced state of the technology. Effectively, gene therapy involves
the introduction of a properly functioning gene into target tissues in
the hopes that it will be translated into a properly functioning protein,
which will mask the malfunctioning protein. Often the new gene is placed
into a modified virus, which is then introduced into a patient in the
hope that the gene will be introduced into a tissue and properly expressed.
Such types of therapy, after
much research on laboratory animals, have now reached the clinical trial
stage. Unfortunately, what works for a mouse does not always work for
a human being. In one highly publicized case, a patient, Jesse Gelsinger,
was given an injection of a virus in the hope of introducing a protein
into the liver. Mouse studies showed good absorption of the gene into
the liver; however, the mouse has a much higher concentration of viral
receptors on its liver cells than do humans. The virus did not absorb
well into the human patient and, for still unknown reasons, created a
massive immune response, causing the patient to die.(31) The original plan for the trials had
been to use the virus only on children in a coma caused by the lack of
the particular liver enzyme; however, ethical and safety reviews caused
the researchers to change the trial direction and use adults only. Many
questions are now being asked regarding the ethics and scientific judgment
of those performing such clinical trials. How well are "volunteer"
patients informed of the possible risks and benefits? How objective are
investigators who have equity in the companies that are funding the trials?(32) One of the risks at this stage of gene
therapy is the excessive public anticipation, created in part by some
researchers, with respect to future benefits. This anticipation may turn
to public distrust of science, if the benefits fail to be realized and
problems such as that in the Gelsinger case continue to occur. Some clinical
trials have shown positive results,(33)
and so there is still hope that somatic gene therapy will become a powerful
One of the problems some
fear might result from knowledge of the human genome is the emergence
of a whole population of socially marginalized individuals, unable to
obtain a job, a family, insurance, or health care and stigmatized by the
rest of society. Insurance companies already insist that those identified
at risk of Huntingtons disease must take a genetic test. If the
results are positive, insurance is frequently refused. Insurance companies
are on record as saying that if genetic information was available, they
would use it in their risk assessment.(34) In Canada, the refusal to insure a Huntingtons
patient does not have dire consequences; in general, public insurance
covers many aspects of care, though the level of care varies across the
country and the coverage for pharmaceuticals is less clear. In countries
without a public health insurance system, however, the plight of such
a non-insured person can be a nightmare.(35) Care may be available but finding it is very difficult.
As more genetic tests become available, insurance is likely to be more
and more expensive for those carrying what the insurance companies deem
to be risky genes. The public insurance schemes may also start to feel
the pressure for such genetic testing, and be forced to make policy decisions
based on the funding available and the knowledge of genetic predisposition
to disease within populations. Gene therapy is at the experimental stage
at this point but will certainly be very expensive when it first comes
into regular use. Who will pay for it? If not public insurance, will the
therapy be available only to rich people, thus creating an ever widening
gap between groups in society, based on both money and genetic inheritance?
Employers may also want
access to genetic information. Some genes might reveal a susceptibility
to environmental damage that was incompatible with a certain workplace
environment. Employers might choose to screen out workers carrying that
gene rather than trying to improve the environment. Individuals with genes
associated with certain behavioural traits might also be excluded from
Some action has already
been taken to prevent the possibility of genetic discrimination. For example,
President Bill Clinton has signed an executive order prohibiting federal
departments and agencies from using genetic information in any hiring
or promotion action. He has also endorsed an Act, introduced in 1999 by
a Senator and a member of Congress, that would extend such protection
to the private sector.(36)
Many of the ethical, legal
and social issues that are being discussed with respect to the Human Genome
Project are not new. Genetic tests for a variety of diseases are currently
available and some people are already struggling with the ethical and
practical implications. What will change over the next few years, as a
result of the Human Genome Project, is the scale of the issues and how
society will have to cope with the greyer areas of genetic disease and
disability. Dealing with a single gene that causes death or chronic disability
is one issue, dealing with whole sets of genes whose impacts vary depending
on environmental interactions is another. The rate of scientific advancement
has tended to outstrip the legislative capacity of governing bodies and
there has been some media "overhype" with respect to genetic
research and its potential for treatment of disease. It will be years
before many of the genetic tests are available and before genetic diseases
can be treated. Society as a whole must use this time to discuss and decide
on how genetic information ought to be used, before the choices are made
for them. It is a discussion that those with genetic dispositions to diseases
such as Huntingtons have long wanted to make more public.
(1) White House Press
Release, "President Clinton Announces the Completion of the First
Survey of the Entire Human Genome: Hails Public and Private Efforts Leading
to This Historic Achievement," 25 June 2000.
(2) Gabor Mate, "The Human Genome: Decoding
the Hype," Globe and Mail (Toronto), 6 July 2000.
(3) Dr. Mike Schultz, as cited in Doug Beazely,
"Gene Projects Answers Come with Risks," Edmonton Sun,
3 July 2000.
(4) Eric Landers and Robert Weinberg, "Genomics:
Journey to the Center of Biology," Science, Vol. 287, 10 March
(5) Stephen Scherer and Lap-Chee Tsui, "The
Unwritten Story of the Human Genome Project," The Toronto Star,
6 July 2000.
(6) A (adenosine), T (thymidine), C (cytidine),
and G (guanosine).
(7) Such offspring have been associated with increased
tolerance to malaria.
(8) Scherer and Tsui (6 July 2000).
(9) Catherine Baker, Your Genes, Your Choices,
(10) Mate (6 July 2000).
(11) Scherer and Tsui (6 July 2000).
(12) Hattori et al, " The DNA
Sequence of Human Chromosome 21," Nature 405, 18 May 2000.
(13) Scherer and Tsui (6 July 2000).
(14) Andrew Pollack, "The Next Chapter
in the Book of Life: Structural Genomics," The New York Times,
4 July 2000.
(15) Michael Hagman, "Mapping a Subtext
in our Genetic Book," Science 288, 12 May 2000.
(16) Human Genome Diversity Project, FAQs,
(17) Catherine Baker,
Your Genes, Your Choices, Glossary.
(18) Andy Coghlan, "Nowhere to Hide,"
New Scientist, 11 March 2000.
(19) Barabara Katz Rothman, "Genetic
Maps and Human Imaginations: The Limits of Science in Understanding Who
We Are," as cited in Gail Vines, "Why Map a Human?" New
Scientist, 29 January 2000.
(20) Barabara Katz Rothman (29 January 2000).
(21) Mate (6 July 2000).
(22) Human Genome Diversity Project, North
American Committee, FAQs,
(23) Lander and Weinberg (10 March 2000).
(24) Nadon J. President and Fellows of
Harvard College v. Canada (Commissioner of Patents) (T.D.),
21 April 1998.
(25) "Human Genes Cannot Be Patented,
Says Assembly," 29 June 2000, http://stars.coe.fr/index_e.htm.
(26) Andreas Russ et al., "Open-Source
Work Even More Vital to Genome Project Than to Software," Nature,
404, 20 April 2000.
(27) John Sulston, "Forever Free,"
New Scientist, 1 April 2000.
(28) Andrew Pollack, "U.S. Hopes to Stem
Rush toward Patenting of Genes," The New York Times, 28 June
(29) John Greenwood, "The Business of
Genes: Newfoundland Hopes to Reap the Benefits after Its Genetic Heritage
Has Helped Decode the Human Genome," The Globe and Mail (Toronto),
24 June 2000.
(30) Rachel Nowak, "Decision Time,"
New Scientist, 8 April 2000.
(31) Eliot Marshall, "Gene Therapy on
Trial," Science, 288, 12 May 2000.
(32) Leon Rosenburg and Alan Schecter, "Gene
Therapist Heal Thyself," Science 287, 10 March 2000.
(33) Marina Cavazzana-Calvo et al., "Gene
Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease,"
Science 288, 28 April 2000.
(34) Laura Landon, "Insurance Giant Wants
Your Gene Map: If the Information Is There, We Would Like to Be
Able to Use It, " The Ottawa Citizen, 6 July 2000.
(35) Huntingtons Society of Canada,
interview, July 2000.
(36) The White House, Office of the Press
Secretary, "President Clinton Takes Historic Action to Ban Genetic
Discrimination in the Federal Workplace," 8 February 2000.