Darryl R. J. Macer, Ph.D. Eubios Ethics Institute
1995
Bioethics
Organ transplantation
Euthanasia
Animal Rights
Assisted Reproductive Technology
Genetic Engineering
Human Genetic Disease
Genetic Screening
Gene Therapy
Other information
of use may be found at the following sites:
books
bimonthly updated News in Bioethics and Biotechnology
Eubios Journal of Asian and International Bioethics,
Bioethics in High Schools in Australia, New Zealand and
Japan.
Access Excellence, Genentech, California, USA
You are encouraged to copy and distribute it
to colleagues and students. I would appreciate receiving comments on how to
improve these materials from as many people as possible.
Please send your critical comments on the
following pages, what subjects could be added or deleted, responses of
students, the classes where it was used, and with how many students...?
Are there any other information sources that
are openly available for people to obtain information from that should be
mentioned. All information would be useful to us, and to other teachers.
Comments will be anonymous unless otherwise requested.
The supplement comes from ideas gathered from
the International Bioethics Education Survey
conducted in 1993, in Australia, Japan and New Zealand. The full report book of
that survey is on -line, Bioethics in High Schools in
Australia, New Zealand and Japan. There are also other
materials available at this world wide web site that may be useful for
examining both the scientific and ethical issues of biotechnology.
The statistical results of some additional
open comment category analysis, and the open comments on what teachers think
bioethics is (including English translation of the Japanese comments) are in
the book, Bioethics for the People by the People, published in May 1994. That book includes the
results of an International Bioethics Survey conducted in ten countries among
the public and university students, and papers from international academics on
bioethics (452pp.).
Please send comments to:
Darryl Macer, Ph.D.
Institute of Biological Sciences
University of Tsukuba
Tsukuba Science City 305
Japan
Email < D.macer@unescobkk.org
>.
To Eubios Ethics Institute Bioethics Resources
1.1. Making choices
Society is facing many important decisions about the use of science and
technology. These decisions affect the environment, human health, society and
international policy. To resolve these issues, and develop principles to help
us make decisions we need to involve anthropology, sociology, biology,
medicine, religion, psychology, philosophy, and economics; we must combine the scientific rigour of biological data, with the
values of religion and philosophy to develop a world-view. Bioethics is
therefore challenged to be a multi-sided and thoughtful approach to
decision-making so that it may be relevant to all aspects of human life.
The term bioethics reminds us of the combination of biology and ethics,
topics that are intertwined. New technology can be a catalyst for our thinking
about issues of life, and we can think of the examples like assisted
reproductive technologies, life sustaining technology, organ transplantation,
and genetics, which have been stimuli for research into bioethics in the last
few decades. Another stimulus has been the environmental problems.
Q1: Can you make a list of ethical questions that you face everyday? Do
you think you will have more ethical problems in the future? Why?
There are large and small problems in ethics. We can think of problems that
involve the whole world, and problems which involve a single person. We can
think of global problems, such as the depletion of the ozone layer which is increasing UV radiation affecting all
living organisms. This problem could be solved by individual action to stop
using ozone-depleting chemicals, if alternatives are available to consumers.
However, global action was taken to control the problem. The international
convention to stop the production of many ozone-depleting chemicals is one of
the best examples yet of applying universal environmental ethics.
Another problem is greenhouse warming,
which results mainly from energy use. This problem however can only be solved
by individual action to reduce energy use, because we cannot easily ban the use
of energy. We could do this by turning off lights, turning down heaters and air
conditioners, building more energy efficient buildings, shutting doors, and
driving with a light foot. These are all simple actions which everyone must do
if we are concerned about our planet, yet not many do so. Energy consumption
could be reduced 50-80% by lifestyle change with current technology if people
wanted to. New technology may help, but lifestyle change can have much more
immediate affect.
Q2: Can you think of conflicting factors between economic interests and
environmental interests? Can you think of conflicting factors between economic
interests and environmental inetrests in the case of petrol? Can you suggest
ways we can save energy ?
Today, science and technology are developing rapidly, and the environment is
deteriorating, so we cannot avoid making decisions. These decisions must be
made by everyone, whether rich or poor. The more possibilities that we have,
the more decisions that we make. Fortunately standards of education are
increasing, but this is no guarantee that the right decisions will be made, as
we often do not think about what we learn in practical life. This is a brief
introduction to the ideals of bioethics, and it is basic to look at how to
balance conflicting ideals.
1.2.1. Autonomy
It is easy to see that people are different, if we look at our faces, sizes
and the clothes that we wear. This is also true of the personal choices that we
make. We may decide to play soccer, read a book, or watch television. We may be
put under some pressure by the people around us to engage ourselves in a
particular activity, or to behave in a certain way, but ultimately it is our
choice. There is a duty to let people make their own choices.
This is also expressed in the language of rights, by recognising the right
of individuals to make choices. Above the challenges of new technologies, and
increasing knowledge, the challenge of respecting people as equal persons with
their own set of values is a challenge for us all.
Some other ideals can be derived from autonomy, such as respect for privacy and trust. Confidentiality is the ideal that we should keep information
another person gives us private, and as a general ideal in medical or business
ethics. The keeping of confidences is also necessary to retain people's trust,
and has been a common feature of business and medical ethics. For example, life
and medical insurance companies may try to take only low risk clients to save
money and be a better commercial competitor by prescreening the applicants for
indicators (e.g. genes) that make them more susceptible to disease. There
should be the right to refuse such questions. The better solution to avoid cost
competition is a national health care system allowing all access to the same
medical treatment. However, it would be cheating the system to hide certain
information from a life insurance company when you knew you were going to die
soon. This brings us to justice.
Q3: How can you respect the autonomy of others more? What are the limits
to personal choice? What factors could we use to make such decisions in your
daily life?
1.2.2 Justice
Our own autonomy is limited by respect for the autonomy of other individuals
in society, and in the world. Those who claim the individual autonomy comes
above societal interests need to remember that at major part of protecting
society is because it involves many lives, which must be respected. We should
give very member in society equal and fair opportunities, this is justice.
Society should also include the future of society, future generations are also
an essential part of society. People's well-being should be promoted, and their
values and choice respected, but equally, which places limits on the pursuit of
individual autonomy. The way that society does that is to impose laws and
guidelines which cover general cases, and the use of a human "judge"
and/or jury to decide the often difficult cases. There is a difference between
what is ethically good, and what can be legally required.
Q4: Can you think of any cases where the ethical principle of justice and
legal justice may be different?
1.2.3. Love: to do good while avoiding harm
A fundamental way of reasoning that people have is to balance doing good
against doing harm. We could group these ideals under the idea of love. Human beings are spiritual beings, sharing emotions
such as love and hate, greed and generosity. An ethical system which fails to
acknowledge this is destined to fail.
One of the underlying philosophical ideas of society is to pursue progress.
The most cited justification for this is
the pursuit of improved medicines and health, which is doing good. A failure to
attempt to do good, is a form of doing harm, the sin of omission. This is the
principle of beneficence. This is a powerful impetus for further research into
ways of improving health and agriculture, and living standards.
However, the precise outcome of interventions in nature or medicine is not
always certain. This uncertainty can be called a risk of failure or chance of
success. Ignorance of the consequences means caution in using new techniques,
and in our actions, so we avoid doing harm.
1.3. Duties to Animals
The above ideals mainly refer to human-human interactions but we have other
interactions in our life, with animals and the environment. These interactions
may involve other ethical factors beyond the consequences they have for people.
Philosophers can argue that the most common morally significant difference
between animals and plants is the capacity to feel pain. In practice one
important criteria we use in judging the use of animals is avoiding the
infliction of pain. (The sheet on Animal
Use has a list of other arguments people use). There is some debate,
about autonomy in animals, i.e. can they think? It is accepted that humans possess unique moral wills, which is the
basis for autonomy. Do animals also have some capacity for free moral
judgement?
The example of animal rights brings us into an area of values. Remember that
bioethics considers both biological data and values. Whether the soul of a
chimpanzee is different to a human soul has been debated for millenia, and is a
question already found in many religions, but actually not usually answered. It
is a question only God can answer, not humans. It is a non-scientific question,
like many other important questions of bioethics, the value of life, the value
of love, and the meaning of existence. Scientific questions are those we can
disprove by experiment, and there are many that we cannot. The concept of
evolution means we see humans as living creatures derived from other living
forms; and the concept of creation would say we are all God's creation. Both
concepts leave us trying to answer value questions.
A scientific question would be to examine how similar the DNA of humans,
chimpanzees and mice are. Within a year or two, and certainly within this
decade we will obtain the gene sequences of all of the human genes that are
involved in our life, including up to 75% which may be involved in determining
our behaviour. Behaviour is influenced by both genes and environment.
Comparison of the genetic similarities and differences to other animals has
many implications. This will change the way we think, and will help develop
bioethics. We can see behavioural patterns in all animals, and increasingly
sophisticated ones in so-called higher animals. The origins of our selfishness
and altruistic (giving) behaviour are fundamental to how we behave (See the
sheet on Genetic Disease).
Q5: Would it change your opinion of rabbits if we find there are only 100
genes different between them and humans? How much do you think behaviour is
genetically influenced, and how can we study this?
1.4. Stewardship
Whether or not nature itself has "rights", we certainly do have
many duties to it. We should not manipulate it solely to satisfy human desire.
An extension of love to other species could be considered under the concept of
stewardship. It has often been forgotten in the past, but has a long history in
many religions, being central to a Judeo-Christian doctrine of creation.
Usually people prefer to neglect it and to think of dominion of humans over the
earth, treating the earth with little value, however we see what problems this
has caused. There are numerous pollution problems that we can readily see,
which affect humans and other species.
Of special attention for bioethics is the value of biodiversity. The
inter-relatedness of all living organisms can be readily seen. All organisms
need water, all organisms have the same genetic code and share similar genes.
All creatures appear, at first sight at least, to be temporal, they live and
they die. This relatedness is expressed by the idea that they are all alive.
While we can argue for human benefit from biodiversity, is there any ethical
value in maintaining different species?
Q6: What advantages does biodiversity have? Which place around your
school has the most biodiversity?
To News on Environmental Issues
How do we balance protecting one person's autonomy with the principle of
justice, that is protecting all people's autonomy? Utilitarianism (the greatest
good for the greatest number) will always have some place, but it is very
difficult to assign values to different people's interests and preferences.
Different people's interests will conflict, so that there are exceptions to the
maintenance of privacy and confidentiality. Many medical and environmental
technologies are challenging because they involve technology with which both
benefits and risks are associated, and will always be associated. Human beings
are challenged to make ethical decisions, they have to. The benefits are great,
but there are many possible risks - including doing nothing.
There is also the idea of slippery slopes. Sometimes if we perform some action, we will perform another. This
expression envisages a slope where once footing is lost it cannot be regained,
and suggests that controls which are adequate for initial exploration may fail
under increased pressure. While we may not do any direct harm with an
application in question, it could result in progressive lowering of standards
towards the ill-defined line beyond which it would be doing harm. The inability
to draw a line is no measure of the non-importance of an issue - rather some of
the biggest fundamental questions in bioethics and life are of this nature.
Different people have different goals and can have different values. Diversity is part of what we call being human. We should
never expect all people to balance the same values in the same way all the
time. Surveys and experience finds that the complete diversity of attitudes and
characters of human individuals are represented in any one society. For
example, we find similar proportions in each society that believe abortion is
wrong, or a women's choice. A failing of human thought is that people view their
society as being different from another, with sweeping generalizations. Such
thinking is often tied to discrimination.
Q7: Can you think of examples of discrimination that you have seen? What
do you think is the cause of these? What can we do to decrease it?
One of the assumptions of bioethics is that all human beings have equal
rights. There are universal human rights
which should be protected, and recognised. We can argue for the foundation of
human rights from secular philosophy or religion. This is different from saying
everyone is of equal use to the world, and the concept of human rights tries to
separate human beings from the concept of how useful a person is.
Despite the scientific world view that is prevalent among academics, most
other people find religions to be a much more important source of guidance in
life than science. In questions of ethics, this is true of most people. Any
theory of bioethics that will be applied to peoples of the world must be
acceptable to the common trends of major religious thought, and must also be tolerant
of differences.
These ideals and issues all need to be balanced, and many people already attempt to balance them.
The balance varies more within any culture than between any two. Perhaps a
mature person and a mature society is one which has developed some of the
social and behavioural tools to balance these bioethical principles, and apply
them to new situations raised by technology.
In order to have a sustainable future, we need to promote bioethical
maturity. We could call the bioethical
maturity of a society the ability to balance the benefits and risks of
applications of biological or medical technology. It is also reflected in the
extent to which the public views are incorporated into policy-making while respecting
the duties of society to ensure individual's informed choice. Awareness of
concerns and risks should be maintained, and debated, for it may lessen the
possibility of misuse of these technologies. Other important ideals of
bioethics such as autonomy and justice need to be protected and included in the
benefit/risk balancing.
Following are two examples of bioethical issues, organ transplantation and
euthanasia, which give some further explanation of bioethics. Separate
information sheets on other issues give fuller discussion of issues such as
ethical limits of animal use, reproductive technology, genetic engineering,
genetic disease and the human genome project, genetic screening and gene
therapy.
One of the techniques of modern medicine that has caught the attention of
the media is that of transplanting organs from one person to another to treat
disease. Blood transfusion is the most common type of exchange, and is used in
many operations and accident emergencies. A few people, for example Jehovah's
witnesses, reject this and their choice is usually respected using the
principle of autonomy, though parent's choice may be overruled sometimes to
save the life of a baby. Bone marrow transplantation is a much newer technique,
used to treat leukemia, and some immune diseases. The issue of sperm and egg
donation is special, given the potential to make a person, and is discussed in
the sheet on Assisted Reproductive Technology.
The transplant of the solid organs, such as kidneys, heart, lung, liver,
pancreas, intestines, etc., is what people generally think of when they hear
organ transplantation. Kidneys are special because we have two and it is
possible to take one from a donor and transfer to a recipient, and the donor
can live with little risk of their remaining kidney failing. Recipients of a
new kidney have a reliable success rate of long term survival (e.g. 90% over
five years is common). "Live donors" are common, there are also
donations from dead bodies. However, there is still a shortage of organs as
only some people who die give their organs for transplant. If you have one
kidney available, and you have to chose one person from two to give it to two,
to save their life, how do you make the choice?
The basic options to this difficult question are to use a lottery, to use a
waiting list, to use age, potential benefit to that person for quality of life,
potential benefit of that person to society, or responsibilities of the person
to others. Among the debated issues one finds most favour for the last factor,
or the waiting list. A mother or father of five young children usually is said
to have more responsibilities than a single person. The death would directly
affect more dependents, so the route of minimum harm is chosen. Against making
the choice is the view that all have equal rights, so the people should follow
waiting lists.
Another related dilemma is the access to organ transplants and ability to
pay. The economic problems of hospitals
who perform transplants have made some Australasian hospitals allow paying
patients to have access to heart transplants, which in turn subsidise the
operation of the transplant unit so that it can provide general services under
public health systems for the majority who cannot pay (at least the full cost).
In some cases the absence of the extra funds would mean the closure of the
unit.
Q8: Should people be able to sell their kidneys? What do you think of the
kidney trade between the developing and industrialised countries?
This could exploit poor people in developing countries, but others argue we
can sell any services. It is now possible to transplant parts of a liver, and
livers can regenerate. This however is still not routine. Heart transplants are
more common, and have a good outcome in general.
In the future we can expect some artificial organs, but for the next decade or two, the major organs will have to
be organic. Another source of organs is from animals, but usually much more
immunological rejection occurs than for human organs. Genetically
engineered pigs have been made to contain
human organs as future sources of organs. Is this any different between using
animals as organ donors and eating animals?
For the moment the source of organs is dead bodies. In Australia and New
Zealand we have a system of donor cards and also state donor status on driving
licenses. We chose to donate, should we die, this is called "opting
in". In most of Europe the system is called "opting out", or
presumed consent. If you don't want to donate organs you have to say so. This
is to attempt to gain more organs, as many people are apathetic to making the
decision.
Q9: In a publicly funded health system, should we have an opting in or
opting out system for organ donation when we die?
The quality of life is more important for most people than the length of
life. There is little value in being alive if the quality of life is terrible.
This issue is something most can agree on. The issue that causes debate is
euthanasia, which literally means "good death". The value decision is
whether we should have a right to end our own life, and when we should do so.
If we believe in God, we may believe that our life is God's, and even if we
don't, we may believe in natural death.
There are two basic divisions of euthanasia, passive and active. Active euthanasia means taking active means like a drug,
or committing suicide, with or without the assistance of a doctor. The law in
the Netherlands allows active euthanasia to be requested, under controlled
circumstances to ensure consent. In 1992 about 2% of the total deaths there
were in this way. In 1996 Northern Territory in Australia will allow active
euthanasia for conseting individuals.
In passive euthanasia we stop
seeking extraordinary medical treatment. One of the early statements on the
distinction between extraordinary and ordinary treatment came from the Pope
Pius XII (1957); "We are normally held to use only ordinary means,
according to the circumstances of the situation, but are not obliged to any
grave burden for oneself or another to life... Life, death, and all temporal
activities are subordinate to spiritual ends."
Q10: Is there are difference between acting to cause death (e.g. pulling
the plug out of the respirator) and failing to act to cause death (e.g. to stop
using antibiotics to fight pneumonia in a terminally ill person)? What factors
are relevant to making an ethical decision in both these cases?
What do you think of continuing intensive care for people who are in a
hopeless situation, if this means other persons who may have more hope of
recovery cannot be put on the life support equipment? Turning off intensive
care is also related to justice. Considering justice we may consider quality of
life as one factor in distributing limited resources, and in fact if we don't,
we are ignoring other people's lives. If we have limited health budgets we have
to make difficult choices, as not only organs are limited, but as in most
services, money is also limited.
The quality of life relates to the individual person, and conceptions of it
change with time and situation. People have different hopes and ambitions, and
the capacity for personal growth from a given state is important. Recently
advance directives, or living wills,
have been introduced which allow people to make choices before they reach a
situation where their quality of life will become very bad and hopeless. These
also take the burden of the decision off family members, and may also be
legally necessary to opt out of intensive treatment. We do not need to maintain
life at all costs, as this may not be in the patient's best interests.
2.1. What are animal rights?
Animal rights makes the claim that
animals have certain rights, which mean that human beings have the
corresponding duties towards them. While we would all agree that we have some
duties to animals, there is much division about just how many and what kind of
duties we have. Everyone has some limits to how they treat animals, and this
summary is intended to look at some of the relevant issues. We come across
these issues every day when we eat animals, have animals as pets, or use the
products of animals.
Even if we disagree with a person's view of life, perhaps it is part of our
duty out of respect for others to try to understand them. In most people's minds there are some
differences between animals and plants. All people are members of the species
Homo sapiens, one of the millions of species alive on the planet Earth.
Fundamentally we should ask whether humans are a special form of life,
different from other living creatures? We must also compare humans with other
species and see where differences may be.
Q1: Is there an ideal of doing no harm to living organisms? What reasons
could we use to explain why people don't like to pull out plants from the garden?
What is a weed?
2.2. Factors for judging animal use
If we are going to harm life, a departure from the ideal of doing no harm, it must be for a good motive. Such a motive might
be survival, and we can see this as natural - all organisms consume and compete
with others. Plants compete with each other for space to grow, animals eat
plants or other animals, bacteria and fungi also compete for resources and
space - sometimes killing other organisms and other times competing without
direct killing. Destruction of nature and life by humans is caused by two human
motives - necessity and desire. Basically, it is more ethically acceptable to
cause harm if there is necessity for survival than if it is only desire. This
distinction is required ever more as human desire continues to destroy the
planet.
Beyond the motive, another important criteria we use in judging the use of
animals is avoiding the infliction of pain. Philosophers can argue that the most common morally significant
difference between animals and plants is the capacity to feel pain. Pain is
more than sensation of the environment, and plants do send ionic potential
signals in response to harm, that are similar to action potentials in animal
nerves. The difference is in the processing of those signals to become the
perception of pain. Some distinguish pain from "suffering", but they
are both departures from the ideal of avoiding harm. Suffering can be defined
as prolonged pain of a certain intensity, and it is claimed that no individual
can suffer who is incapable of experiencing pain. The capacity for suffering
and/or enjoyment has been described as a prerequisite for having any interests.
Q2: Is pain always bad? Is causing pain bad? Do different people feel the
same amount of pain?
Judging pain is subjective, and there are parallels in the way animals and
humans respond. Many of the neurotransmitters are similar between higher
animals and humans. It is possible that animals do have a different quality of
"pain", as the frontal region of the cerebral cortex of humans is
thought to be involved in feelings of anxiety, apprehension and suffering
components of pain. This region is much smaller in animals, and if it is
surgically treated in humans it can make them indifferent to pain. There are
differences seen in the types of pain receptors, some respond to mechanical
stimuli, some to noxious or irritant chemicals, and some to severe cold or
heat. The difference between pain of animals and responses of plants (which
include electrical response like animals), is that a signal is only a signal,
whereas pain is something after the reception and processing of the signal in
the nervous system.
We can think of ethical factorsto do with the organism itself, and others
which are external to it. A summary of some factors for judging animal use are
below:
Intrinsic Ethical Factors
- Pain
- Self-awareness
- Ability to plan for the future
- Value of being alive?
Extrinsic Ethical Factors
- Human Necessity / Desire
- Human sensitivity to animal suffering
- Brutality in Humans
- Other animals upset (e.g. family mammals)
- Religious status of animals
- What is natural
Q3: Have you ever used animals for experiment classes? We can think about
how we treat animals at that time. Can you think of intrinsic ethical factors,
and extrinsic ethical factors for your study?
At the practical level, the feeling of pain is the first major guiding
principle for animal treatment. The second depends on the concept of autonomy,
if they have self-awareness such as higher apes, and probably other animals
such as dolphins. We do need to consider the findings of animal studies on the
level of self-awareness that some may possess. There is growing evidence to
support the concept that higher animals have self-awareness, and it will be aided
by genetic and behavioural studies.
2.3. In practice
Some people make the value choice not to eat animals, and become
vegetarians. This also may have some environmental advantages, as energy is
wasted in the transfer from plants to animals. However, others say it is only
natural for us to eat animals, the scheme of nature, or God, and we should just
minimise harm we cause. Many people will continue to eat animals, and practical
ethics must improve the ethical treatment for all animals.
One area of particular concern is whether animals should be in a field or in
a caged box, or factory farm. The main
ethical question is confinement of animals, such as veal calves, pigs and
poultry in small cages. There have been several countries which have banned the
use of battery caged hens. It has been illegal to use battery cages in
Switzerland since 1992. People need to decide how much more they are prepared
to pay for better treatment of animals, such as the costs of eliminating
battery farming, or the costs in not using new animal treatments that produce
cheaper milk or meat such as bovine growth hormone. The consequences on the
different communities involved in agriculture of these decisions also needs to
be considered, a variety of external factors, some of which will be discussed
later.
To understand life can make us appreciate it more. Another question that can
be asked is whether we should keep animals in zoos. Zoos and wildlife parks can have some value in
preservation of endangered species, and in gaining public support for
conservation campaigns. However, in practice not many zoos world-wide actually
do this. How can you measure this, and do you have local parks to visit? Should
we capture animals for the purpose of keeping them in zoos, and under what conditions
would the capture of animals be ethical?
The issue of animal experiments has
caused much debate. In some sense it is a little ironic because most people eat
animals, which is a choice based on desire more than necessity; whereas some
animal experiments, e.g. models of human disease or therapy, could be more
necessity than desire. In the past decade there have been less animal
experiments conducted, and we can expect more ethical alternatives to continue
to be developed. The choice of the alternatives is also often made for cost and
efficiency.
Q4: Can you find examples of medical advances in which animal research
was essential?
Some of the factors that are used in
the guidelines to assess whether animals should be used in experiments or not,
include:
- Aim of experiment
- Realistic potential to achieve goal
- Species of animal
- Pain likely to be involved
- Duration of discomfort or distress
- Duration of experiment (in terms of lifespan)
- Number of animals
- Quality of animal care
- Alternatives to experiment
Q5: Can you list examples of each factor, and suggest any more? Which are
the most important?
Q6: In the animal experiments you have done in class, discuss what
benefits and what you learnt? Did it change your attitude towards animals? What
are the differences between using an animal killed accidentally and one that
was grown and killed especially for an experiment?
In a survey of bioethical issues
conducted in Australia, New Zealand and Japan in 1993, there was much division
over whether animal experiments were necessary or not. Some teachers took
strong positions on either side of the question whether some animal experiments
are necessary to teach biology in high school. There are also many types of
experiment, for example, observation in nature, in the class, dissection, and
some experiments were described that caused painful death to vertebrates. The
purpose of this summary is not to take sides, but we should ask the question
what type of experiment is necessary, and how much is learnt.
In 1993 a book was published calling for equal rights for chimpanzees,
Gorillas, and Orangutans with human beings. It is claimed that these four
species of higher primate form a more natural group to confer ethical duties on
than it is to put human beings on top, alone. Those who want to see their
declaration should write to "The Great Ape Project", P.O. Box 12838, A'Beckett Street, Melbourne,
Victoria 3000, Australia.
Q7: Discuss the Great Ape Project in class. Can you think of any reasons
to think that we have more duties to human beings than other primates? What
about dolphins and whales?
2.4. Moderation and balancing
It is not likely that anyone will actually go on to do experiments on
chimpanzees in their life. However, it is extremely likely that you will eat
fish, swat a fly, cook a steak, use products or drugs developed with animal
experiments, and at least use the money supported by exports of animal products
for your education. If you study biology you probably want to understand how
animals can live, and sometime you need to see animal experiments, whether in
life, or on video, or in a book. The impressions from each example can be
different.
Our bioethics must have a basis from all data, including reasoning,
philosophy and biological knowledge. Absolutes are often difficult, but it is
ethically important to make balanced choices. It is ethically consistent to try
to use lower organisms, cells, or computer models, if possible, for animal
experiments, but at some stage of testing both animal and human trials are
necessary.
Perhaps the most important lesson to learn is that life is not so easy, and
neither is bioethics. To make an
ethical decision means balancing
alternatives, and benefits and risks of harm. One way to do this is to think
about the factors that are involved on each side and reach a decision.
Different people may do this a little differently, perhaps the final question
of animal rights is how much right do people have to chose different answers.
3.1. Infertility treatment
There are many couples who are unable to have children, and if these couples
cannot have children after attempting naturally for around a year, we could say
they are infertile. The proportion is
approximately 10%. We should also recognise the frustration of couples who
desire to have a family genetically related but are unable to achieve this on
their own. In our society there are many pronatalistic ideas putting pressure
on couples to have children, and there may be a shortage of children for
adoption. Recently more people make the choice not to have children, or to
delay having children, but the majority of people have a natural desire to have
children.
Since 1978, when the first baby was born with IVF in the UK and soon after
in Australia, much media attention about human reproduction has focused on in
vitro fertilisation (IVF). A technique
which has resulted in the birth of tens of thousands of children to infertile
couples. There are various ways to overcome infertility, including induction of
ovulation, surgery, and artificial insemination, which may be used in 85% of
cases. The use of IVF and related techniques may treat 10-15% of cases.
Approximately only half of infertile couples can achieve a pregnancy, sometimes
this is because they run out of money trying these techniques.
The oldest method involving only the married couple as sources of gametes is
artificial insemination (AIH), where semen of the husband is implanted into the
wife. The oldest recorded case was in 1790.
There are several major phases in the technique of IVF. First the woman is
treated with a stimulator of follicular growth, then the oocytes, or egg cells,
are removed by aspiration and collected. The oocytes are usually collected by a
technique called laparoscopy, where the oocytes are aspirated from the
follicles in the ovary. Male semen is combined with the oocytes to fertilise
the eggs. This part has a high success rate, often 80%, for patients to
fertilise the eggs. These embryos are grown to a multicell stage before
implantation. Three embryos are normally implanted with the rest of the embryos
being frozen, to be used for another attempt to produce a child. The success
rate to have a baby varies between clinics but is often around 15% per
implantation attempt. This compares to a unassisted normal implantation rate of
30-40%.
A recent alternative to IVF is gamete intrafallopian transfer (GIFT), in
which the mother receives hormonal treatment to stimulate ovulation, and
produces several ova. Some of these are then placed, together with a concentrated
amount of a sperm, in her fallopian tubes. Fertilisation occurs normally, in
the body. The success is at least as good as IVF.
Fertile people may have a need for infertility treatments also. People who
undergo radiation treatment, especially women, may want to store eggs for use
after therapy. Some chemotherapy agents also can cause mutations. 3.2.
Ethical issues of IVF
The moral status of the embryo is an important question, as some embryos may
be discarded if not all are used in IVF. Spare embryos can be frozen, and used for another attempt at embryo transfer,
and this is routine in some clinics. To lower the risk of multiple pregnancy
only three embryos are usually transferred per attempt. Freezing avoids wasting
the embryos, and the survival rate for embryos is greater than for oocytes. It
avoids the need for oocyte recovery from the mother before every attempt. It
has not been found to be associated with any risks to the child. It does
present several important ethical and legal issues, after the couple have a
successful live birth, on the disposal of the frozen embryos (as well as the
disposal of unused sperm and oocytes). The embryos may be used for a future
attempt by the donor couple, or they may be donated, or discarded, or used for
research prior to discarding.
There are a variety
of arguments which have been expressed in debates about IVF.
Arguments against IVF include
- unnatural
- treating a desire not necessity
- child as consumer item
- changing society
- too many children in the world so we don't need it
- costs too much (do you know how much?)
- some embryo experiments are used to increase the success rate, and the
potential for future eugenics
Arguments for IVF
- "human right" to raise a family
- it is done in love to help make human life
Q1: Can you think of any other factors? Which of these factors apply to
other approaches to treating infertility?
There have been objections from the feminist movement to IVF, because they think that it reinforces social attitudes concerning the imperative of biological parenthood (with the stereotype of women as child raisers); it increases the possibility of exploitation of women; there are possibilities such as sex selection (which is often based on a low value of female over male); the commercialisation of gametes, embryos and women, so they are viewed as commodities; and the experimental nature of the techniques. These include some of the issues discussed above.
Q2: Which of the concerns about IVF are unique to IVF and are not shared
by other medical treatment?
In principle IVF and artificial insemination are accepted means to aid
infertility to married partners, using semen or eggs within the marriage, by
most people. However, in many countries IVF is not publicly funded, because it
is considered more as a desire than necessity, given the shortage of money for
health and more urgent life-saving needs.
There is an interesting question of whether prospective parents should be
screened for their suitability to have children. Assisting single parents or
homosexual couples to conceive a child may contribute to specific negative
child-rearing conditions in most cultures, but we need to remember that one
quarter or more of babies born today are born out of marriage, and the high
divorce rate.
Q4: Should we assist the use of medical treatment to aid people to have
children who are in an unusual parenting situation? While we cannot enforce a
law to make the birth of a child a crime, can we decide who is in a more
desirable situation to raise children?
3.3. Sperm and egg donation
Sometimes one member of a couple may be incapable of producing gametes which
can lead to fertilisation. Also, the couple may not be infertile, but one may
carry a major genetic defect and so would not like to take the chance that the
offspring also suffer from that genetic disease. If these couples do not
consider adoption a possible option and
still want to have children, then they may consider use of artificial
insemination using donated semen (AID) or IVF where the egg, or sperm, may come from another person.
3.3.1. Artificial Insemination
The oldest case of medically assisted AID was in 1884, but it was seldom
used until the later half of this century. The success rate per patient after
three months is about 40%, and it is used around the world. The involvement of
a third party in marriage is an
objection to AID many have. However, in second marriages where one partner may
bring children of a previous marriage, there are similarities. In France
couples who have children by AID have a 2% divorce rate, lower than general,
and psychological studies of the children suggest no ill effect.
The two sources of extramarital gametes that are commonly used are those
donated by relatives or friends, or those from completely anonymous sources. Because of the risk of a conflict of
attitude toward an offspring from an identifiable non-parental source,
anonymous donations are preferred. In New Zealand and Sweden the child can find
the identity of the genetic parents, like adopted children. Some would say that
if the parents do not tell their children that they are not their genetic
parents, it is always going to be a deceitful relationship.
Q5: Children may also want to know their origins. Do they have the right
to know their biological parents? At what age? Is it the same as adoption? What
other reasons are their to keep medical records of the donor? How much choice
of characters (e.g. race) should parents have when selecting the donors?
3.3.2. Surrogacy
It is possible to separate both genetic and social parenthood from
physiological parenthood, as in the case of surrogate mothers. There are strong
opinions on the use of surrogacy, and conflicting laws in many countries or
states of the same country. There already are over a thousand children born
(mainly in the USA) who joined their genetic parents who become the social
parents, after birth.
Q6: How many different mothers can you have? Who should keep the baby if
the surrogate mother decides to keep the baby after signing a contract which
said she would give the baby to the genetic parents after birth?
Q7: Is commercial surrogacy morally wrong? Is the gift of a womb different
to the gift of blood?
3.3.3. Regulations of AID and Surrogacy
Because IVF requires technical assistance some controls can be made, but the
techniques of sperm donation and surrogacy are ultimately beyond the control of
medical authorities. People can donate sperm and use some form of surrogacy,
e.g. insemination with the sperm of a man, donated egg of the surrogate mother,
and arrangement of the child to be given to the genetic father (and usually a
wife), without medical assistance. In fact there is a case in the Bible, with
the first child of Abraham.
The laws in different countries are mixed, reflecting the difficulty of
deciding these issues. For example, in Germany egg donation is illegal but
sperm donation is not. In order to try to protect the interests of the future
babies and mothers, some medical advice and assistance is useful, making a case
for relaxed laws. The counter-argument is that we should not offer medical
assistance to what is not accepted by the common morality of our society.
3.4. Embryo experiments and cloning
Skills in human embryo manipulation are improving. Preimplantation
diagnosis, or biopsy, is where a cell of
an early embryo (e.g. 1 from an 8 cell embryo) is removed, and the presence of
genetic disease can be assessed in about 6 hours, then the embryos without the
genetic disease chosen to be implanted in the mother. Babies began to be born
from this technique in 1990.
Robert Edwards, a pioneer of IVF, suggested in 1984 that making identical
human twins could be useful in IVF as twin transfers give higher rates of
implantation than single transfers. When it is only possible to obtain a single
embryo from collecting eggs, it would increase the chances of a pregnancy if
that embryo was split. Animal studies suggest this would present no extra harm
to the babies born. In 1993 scientists reported experiments on splitting human
embryos, and the growth of these "cloned twins". It has probably been technically possible for several
years. Most mammalian embryos can only be split into 2-4 clones, after that the
cells lack the ability to start development into a human being.
Q8: Is there a difference between identical twins made in nature or ones
made by human cloning? Such clones could be born at different times and/or from
different mothers? Are they still twins?
Q9: Do you think Assisted Reproductive Technology is a waste of
resources, considering the population problems for the world as a whole?
To News on Assisted Reproductive Technology
Genetic engineering encompasses those techniques that manipulate genes,
especially those using recombinant DNA techniques. The purpose of genetic
engineering is to introduce, delete or enhance a particular trait in an
organism. This is achieved by either inserting foreign genes, or by altering
the existing genetic make-up of the organism. It may involve replacing a single
DNA nucleotide, or multiple genes which are thousands of nucleotides in length.
Genetic engineering is only part of biotechnology.
Biotechnology could be called the use or development of techniques using
organisms (or parts of organisms) to provide or improve goods or services.
Biotechnology itself is part of an expanding technology based on a long
foundation of human use of living organisms, for example, agriculture and
making beer.
Genetic engineering relies on the use of enzymes. Restriction
endonucleases cut DNA at short, specific
base sequences. This allows DNA to be chopped into smaller pieces, and DNA-ligase can join the ends of desired pieces to other DNA.
The nucleotide sequence that acts as the enzyme recognition signal usually
contains the specific nucleotide that the cut is made at. Using these enzymes
new pieces of DNA can be incorporated into carriers called vectors. To allow specific joining of the inserted DNA into
the vector, the sticky ends must correspond. If the inserted DNA does not have
the correct nucleotide sequence, then short synthetic nucleotide sequences,
called linkers, can be added to
the ends of the insert DNA before it is joined to the vector.
The vector used for genetic engineering is usually a virus or plasmid (in bacterial cells). These plasmids or
viruses normally multiply in the cell, and will also do so with any inserted
foreign DNA. For insertion into mammalian cells the DNA is usually incorporated
into the cell's chromosomal DNA. This may occur by use of an intermediate
vector such as a virus which normally inserts itself into the chromosome. The
joining of DNA is called recombination, and recombinant DNA technology allows the Earth's entire genetic
resources to be exploited by providing a means of overcoming natural barriers
of gene transfer. We have also found that some interspecies "genetic
engineering" has been occurring in nature, and DNA is more fluid than was
first thought.
Q1: The bacteria in your gut exchange DNA with each other, and take up
DNA from your dead intestinal cells. What is the difference between this
genetic shuffling and genetic engineering performed in a research laboratory?
There are also some methods to directly insert DNA into chromosomes, using a
natural phenomenon called homologous recombination. This is where matching DNA sequences match up and a
break in the DNA occurs allowing insertion of the intermediate piece of DNA. In
this case only DNA between the recombination sites that match those on the
chromosome are inserted is the new insert, there may not need to be any vector
DNA, such as viral sequences, inserted into the DNA. It is possible to replace
a chosen nucleotide sequence with a new sequence, between the homologous
nucleotide sites, which is precision genetic engineering. Currently the success
rate of directed gene transfer in mammals is low, so that some selection
mechanism for the cells with the desired genetic change is required.
Q2: Can you suggest any products of genetic engineering that are being
used in your daily life? Did you know your laundry detergent is probably
genetically modified enzyme?
4.2. Medical uses
Many human proteins are now being
commercially manufactured by the use of gene transfer to microrganisms such as
bacteria or yeast, including blood clotting factors, interferons, lymphokines,
growth hormone, erythropoietin, insulin and various growth factors, which have
medical uses. One of the most common proteins in use is human insulin, by
diabetics.
Recombinant DNA techniques are also being used to produce human vaccines and a goal is a cheap, easily stored, vaccine
against major childhood diseases. The logistics of the world-wide immunisation
programmes are influenced more by transport, storage and delivery than
production. Edible vaccines have
also been made in foods, such as hepatitis B vaccine in lettuce or banana (or
Plantain), which may avoid the need for medical staff to administer the
vaccine, and make the plants cheap enough for third world countries. The degree
of expression is not yet high enough for use, but is being improved.
A genetically engineered vaccine
against cattle ticks is being mass produced in Australia, that should help control tick infestation. The
tick is an external parasite, but ingests blood, and the vaccine is a modified
version of a tick protein from the gut cells, which produces immune response in
the cattle which in turn prevents reproduction of the tick.
Modified proteins can be made, using genetic engineering to alter the
catalytic properties of natural enzymes, what is called protein engineering. Many pharmaceutical products can potentially be
made. The medical importance of these recombinant DNA protein products is
growing, and the availability of these products makes therapies for a lot of
previously untreated or uncured diseases possible.
Modified products are also being used in industry, environmental and
agricultural applications, and some as discussed later.
There are obviously benefits of genetic engineering, but we must also assess
the risks and consequences of use. This is sometimes called technology
assessment, and is part of bioethics.
During 1973-1976 there was a voluntary moratorium imposed by scientists on the practise of introducing
foreign DNA into bacteria, following an International Conference in Asilomar,
California. The fears were that moving genes widely could have bad
consequences, for instance it could cause the spreading in the microbial world
of antibiotic resistance, or toxin formation; or that genetic determinants for
tumour formation or human infectious diseases would be transferred to bacterial
populations, which could then infect human beings.
Both physical and biological containment are used. "Biological" containment advocated the use of
"crippled" host cells and vectors, such that these would have no
success in colonising any environment outside that of the contained laboratory
even if they managed to escape from it (e.g. E. coli K12). Since the initial
categories of physical containment were decided on there has been widespread
experience gained in the practise of these experiments, which has resulted in a
decrease in the assessed hazards and thus the type of containment judged
necessary. The principle of biological containment is still used for most
laboratory experiments, especially when dealing with human genes and/or
tumour-promoting agents. Physical containment is not so strict, but is still
maintained for work on tumour or disease-promoting agents.
Q3: If you read the book Jurassic Park, or saw the movie, can you describe
what methods of biological containment and physical containment were used to
control the genetically rebuilt dinosaurs?
Before the appearance of genetically modified organisms (GMOs) there have been harmful effects from some of the
accidental releases of organisms from laboratories. In 1958 tobacco blue mould
(Peronospora tabacina) was brought into the UK for a research institute. In
that year the mould spread to four other institutes, including one in the
Netherlands, and to a commercial tobacco crop in England. In the following year
the disease appeared in the tobacco fields of Belgium and the Netherlands, from
where it spread quickly across the rest of Europe (advancing in Germany at the
speed of 5-20 km per week). After several years of crop breeding resistance was
increased, but it is a powerful example of the risks of accidental release of
new organisms.
There are many more common examples of ill effects of the introduction of novel
species into Australasia, for example
rabbits. The deliberate environmental introduction of any new organism,
including GMOs should be only undertaken within a framework that maintains
appropriate safeguards for the protection of the environment and human health.
Natural habitats already contain their own indigenous populations of organisms,
organised in a delicate web of nature, which needs to be maintained. Recent
introduction of biological pest control agents has been more successful due to
better ecological assessment. We should also note that most food crops and ornamental
plants are introduced species, and are essential for the economic prosperity of
most regions of the world.
4.4.1. Safety of GMOs and Release to the Environment
The environmental release of genetically modified organisms (GMOs) is now assessed by regulatory authorities and trials are common in many countries, including Australia
and New Zealand. Only small scale agriculture can be conducted in semi-closed
environmental systems, though some important products used today are produced
in that way, such as eggs from battery farming of chickens (which raises
ethical questions of farming methods).
There have been many field trials since 1984 when Canadians field tested a transgenic
plant. There is public concern about the
free release of recombinant organisms into the environment, and the degree of
care required depends on the potential risk to the ecological balance and
humans. Scientific methods and experiments are being used to look at the risks,
which include gene transfer and the cross-breeding resulting in new weeds.
There are several factors required for enduring gene transfer: its transmission
to an extraspecific cell; a resulting advantage to the recipient cell; and
multiplication of the recombinant DNA to numbers of copies that would render it
"safe" from random loss. Eucaryote/procaryote gene transfer has been
documented. For crops that make pollen, the pollen may disperse around the
field and could hybridise in some species with wild relatives.
Q4: How can we assess the safety of introducing a new organism into an
environment?
Some of the factors that are relevant to the assessment of the safety are
the type of organism, the gene, the gene product, the probability of gene
transfer to the environment, and into another organism, the effect of
transferring the gene to other species around the field, and the ecological
consequences of any of these stages. In practice it is difficult to predict
until field tests are performed and monitored.
A new tomato variety was made by a technology involving use of antisense RNA sequences to bind to the mRNAs of undesired
proteins. The reduction of the concentration of an enzyme (poly-galacturonase)
which is produced by ripening tomatoes which causing softening of the tomato. The concentration of this
enzyme was reduced by up to 99%, so the fruit stay firm. This enzyme degrades
the cell wall of the cells in the tomato, so its absence leaves the cell wall
firmer. These tomatoes have been developed to improve shelf life (about 300%
longer) and taste since growers can leave the tomatoes on the plant longer.
Q5: What other benefits can you think of from such tomatoes? What other
agricultural uses of genetic engineering do you know?
In the USA over a dozen crops have been approved for open commercial release
by 1996, and many further ones are expected. These crops included the above
tomato with delayed ripening and a herbicide tolerant cotton, described below;
Oil-modified (laurate-containing) canola; Virus-resistant squash;
Delayed-softening tomato; Colorado potato beetle resistant potato;
Insect-resistant corn. They are current examples of approaches of genetic
engineering that are being used.
Further details of the US Department of Agriculture (USDA) GMO guidelines
and field trial release data are on line on the world wide web,
http://www.aphis.usda.gov/bbep/bp/ Between 1987-1995, the APHIS of USDA has
approved or acknowledged 1,590 field trials at 6,133 field sites. Derivatives
of 39 different plant species have been field tested to date, with corn the
major crop being field tested. In 1995 saw the first field trials involving
barley, carrot, cranberry, eggplant, gladiolus, pea, pepper, strawberry,
sweetgum, wheat, watermelon and Arabidopsis thaliana; in addition to many
previously tested.
The New Zealand Interim Assessment Group on regulation of GMOs (Ministry for
the Environment) has annual reports, and the total by 1995 included 33
applications for field trials, glasshouse trials and taste tests. The recent trials
include continued research into sheep with altered growth rates and wool
production; a modified clover with resistance to white clover mosaic virus. A
proposal to import semen to establish a breeding stock of sheep with expression
of the alpha-1-antitrypsin protein as a "bioreactor" was declined,
and the decision is being reviewed following an appeal.
There is research in New Zealand on the control of ripening and softening in
apples. The goals are to improve storage life, as well as quality (texture,
colour, and sugar content). The general improvement of storage properties of
fruits and vegetables is of benefit to Australasian exporters of food. However,
it may be of greater benefit to third world countries who lack the resources to
use cold storage in transport or shops. We could expect more nutritious food
with more vitamins, but see p.12.
4.4.2. Reducing pesticide use
Not all crops are eaten, and a major example is cotton. The BXN bromoxynil resistant cotton varieties had
about 100 field tests in 12 states over 5 years, before being judged safe to
grow. US cotton growers currently apply about 10 million kg of herbicide valued
at US$200 million annually, and this new variety may reduce the herbicide use
to one quarter of the current level. In 1994 season about 4000 acres will be
planted, 3000 for seed production, and 1000 acres divided among 30-50 cotton
farmers for free use in return for data on the herbicide usage and yield, etc.
The US cotton industry is worth about US$4 billion, and weed and pest loss is
estimated to cost US$600 million a year. A more speculative future application
is the development of blue cotton, which may avoid the use of chemical dyes for
clothing manufacturers, which saves both money and environmental pollution.
Bacteria can be used as pesticides, for example, insecticidal proteins of
Bacillus thuringiensis selectively kill the larvae of moths and butterflies.
There are many different varieties of protein, and each is specific to
different insects. Each is made from different strains of this bacteria, and
the proteins are biodegradable. Spores of this bacteria have been used to
control malaria-transmitting mosquitoes for many years. Broad spectrum insecticides kill all insects, which includes spiders and
beetles which are useful predators.
The control of caterpillar pests with plants expressing this insecticidal
gene offers several advantages. Control
is independent of the weather, and in conditions which would be unsuitable for
spraying chemicals or bacteria, the crop is still protected. All parts of the
plant are protected, such as the roots, or new growth previously susceptible
between sprayings. It is also possible to use bacterial sprays containing the
protein, if it is not desired to have the gene in the plant because of food
safety concerns - however, it may cost more to the farmer and be less
effective.
The problem of insect resistance to
this protein is the same as insect resistance to chemical pesticides, i.e.
given time and use insects become resistant. One strategy to control resistance
is to include a few percent of non-modified plants in a field which
substantially reduces the selection pressure that results in resistant insects.
An Australian example is NoGall,
which is a modified bacteria so that it won't cause gall on plants, and it was
the first GMO to be approved for commercial use in the world. Other microbial
applications include the introduction of plant symbionts, such as nitrogen
fixing bacteria, which reduce the need for fertilisers. Mycorrhizal fungi can
be used to increase plant growth rates by improving the efficiency of root
uptake of nutrients.
Q6: What species of bacteria is used for plant genetic engineering? What
other methods of gene transfer are commonly used? What is sustainable agriculture?
The problems of pollution are mainly caused by our own lifestyle and
economic system. They are made worse by the population growth. Efforts to
reduce the amount of pollution, and degradation or removal of wastes are also
being made by genetic engineering and biotechnology. The most global schemes
are the greening of deserts, which may be aided by the breeding of drought and
salt-resistant faster growing plants.
Bacteria can be used to produce polymers that can be processed into
biodegradable biopolymers, e.g.
polyhydroxybutyrate. The genes for polymer production may be put into food
crops, such as potato tubers. This would also avoid using non-renewable and
energy intensive production techniques. The production costs are still too high
for general use, but some medical application plastics are being made.
Animal antibodies can been produced
in transgenic plants, which could also be used to protect plants against viral
diseases, or the antibodies could be used to scavenge small organic pollutants
such as toxins, from the environment. New antibodies can be made, to bind to
different pollutants.
Microorganisms are more difficult to
trace once in the environment, and their survival depends on selective pressure
in the soil or water environment, in the complex and as yet poorly understood
ecosystem involving literally thousands of microorganism species. There have
been, and are many future possible uses of microorganisms in the environment,
and this range is being expanded by genetic engineering. Bacteria can be used
to degrade toxic compounds, such
as heavy metals, organic compounds, phosphorus, ammonia or other pollutants. Biomining is environmentally more favourable, but also is
proving cheaper and enabling the extraction of metals from low grade ores. It
has long been used for copper, and is also being used for gold and phosphate.
The first major use of bacterial degradation of an oil spill followed the Exon oil spill in Prince William Sound,
Alaska in 1988. In this case, genetically modified bacteria were not added, but
fertiliser to allow the low number of naturally occurring bacteria present in
any soil that can degrade hydrocarbons, to multiply. The fertiliser is called
Inipol. The technique is only applicable to beach areas, as the fertiliser will
not cling to rock surfaces. The treated areas were dramatically improved within
fifteen days, and even the underlying soil at a depth of one foot was degraded
within 40-50 days. This was particularly important in the low temperature
arctic environment where oil degrades very slowly. There has also been use of
oil-degrading bacteria in the open sea in an oil tanker accident in the Gulf of
Mexico in June 1990. It would be an advantage to destroy the oil before it
reaches land, and also before it kills marine life. The detergent dispersents
currently used disperse the oil slick so it does not look polluted, but in the
water the dispersed globules may cause more harm to marine life.
Q7: Can you summarise the environmental benefits of GMOs, and identify any
further benefits? Can you balance the benefits and risks of alternatives for
some of these uses, e.g. pesticide use?
Some people think that products made from GMOs are unnatural. We need to
think about existing food varieties and whether they are different. We can find
people with allergies to many foods, and there will always be some people who
have an allergy.
Q8: Is there anything which is intrinsically dangerous in making foods
from plants or animals that are bred by genetic engineering?
Protein pharmaceuticals produced by recombinant DNA technology require
approval, for both safety and effectiveness (efficacy). There are a variety of impurities that are possible, including endotoxin, host cell
and media proteins, monoclonal antibodies, DNA, and infectious agents.
Impurities can have immunological and/or biological effects. New purification
methods have produced the highest purity proteins that have ever been available
for human therapeutic applications. Proteins made using this technology can
avoid the risk of virus transmission, a problem with blood products.
In August 1990 an association between a batch of the amino acid tryptophan
produced by Showa Denko, a large Japanese chemical company, and a disease called eosinophilia-myalgia syndrome (EMS), was
reported. Tryptophan is part of a dietary supplement used to treat insomnia,
depression or premenstrual tension. The outbreak of EMS in USA during 1989 led
to 27 deaths, and can be traced to a particular batch of this amino acid. There
were cases in other countries also. The batches concerned were filtered with less carbon so a contaminant remained, and
also were made using a new strain of bacteria. The cause of the EMS was a
contaminant, so rather than the genetic modification being responsible, the
purification procedure was to blame. However, the case emphasises the need for
any product, food supplement or not, to be checked before use, as the US Food
and Drug Administration (FDA) concluded.
The so-called tasty tomato, Flavr Savr
(Flavour Savour), as discussed above, has been approved for sale in the USA by
the FDA. The tomato is being sold in supermarkets in the USA. Calgene says the
tomato will stay fresh about a week longer, and will use the name MacGregor's.
Other countries will no doubt want to use the tomato, especially those with
difficulties in transport of fresh vegetables, and it has widespread public
approval as seen in international opinion surveys.
Another product of genetic engineering approved in the USA in 1994 is bovine
growth hormone or somatotropin (BST).
When it is given to dairy cows they may make 10-20% more milk. However, there may be a few health effects on the
animals, which could result in increased use of antibiotics in the cows and the
antibiotic residues may be in the milk. After extensive study the product was
approved as safe for humans, but there continues to be controversy. Some
dairies have made advertisements that their milk is "hormone-free",
which is being debated in courts in the USA. The major concerns have been
socio-economic, that this technology will continue the trend towards large farms
making it more difficult for small farms to economically compete, and they
could only compete if milk from small farms was labelled so people who oppose
this trend could select the products. However, several US states have laws
against the use of BST, its use in Europe is being delayed, and people in
countries with enough milk ask why we need more milk. Some countries which
import milk powder, like Pakistan, welcome the hormone as a means to increase
local production.
In the USA, the FDA has said it is not necessary to label food containing products of genetic engineering.
The situation may differ in different countries, and some public groups argue
that it is best to have more information available for the consumer and the
origin is of interest to consumers. The UK government has said that it will
label products contain genes from humans, from an animal that is the subject of
religious dietary restriction, or an animal gene when in a plant or microbe.
The label will say "contains copies of X gene".
Q9: Can you think of the economic effects of genetic engineering in
agriculture? Will it solve the food crisis in the world?
To News on the Safety of recombinant DNA products
5.1. Mechanism of genetic disease
Every person has a different genetic sequence, except for identical twins.
The genes are made of DNA. DNA is a long chain of units, called bases, and there are only four kinds of base (ATCG). Each
position of the DNA can be one of the four base, and the sequence is the order
of these bases. In the same way the sequence of this sentence determines what
we understand in reading it, the sequence of DNA determines what happens in
living organisms. There are only four possible characters for each position,
but even a short sequence of 20 positions could have many possible combinations
of sequence. DNA is a long chain of these units.
Functional lengths of DNA are called genes. Each gene may be involved in defining one particular function or
character at the phenotypic level. Our genes are in long linear strings, called
chromosomes. Humans possess 23 different pairs of chromosomes, a total of 46.
While every human has the same set of chromosomes and thus types of genes in
the same order, each gene has variant types which are called alleles. Alleles differ in their exact sequence of DNA but they
should perform the same function. We can have many different alleles, for
example there are at least 46 distinct alleles of the gene phenylalanine
hydroxylase (a mutated allele is responsible for the disease PKU). [There are
mutations found in each of these alleles, which would make total genetic
screening for PKU impracticable, but a simple cheap enzyme test can be
performed].
The Human Genome Project aims to map and sequence all the DNA of human beings, what is called the genome (a total of about 2.8 billion linear bases on 23 chromosomes). There are thought to be about 70,000 genes in human beings, and most of these have been identified. However the genes comprise only 5-10% of the total DNA in the human genome, the function of the rest of the DNA is unknown. While most genes are identified the function of most of them is still to be investigated. The countries that are involved at the time of writing include Australia, Canada, the European Union (especially France and the UK), Japan, South Korea, and the USA. Up to 5% of the money in some is being spent on the educational, ethical, legal and social impact.
To News on the Human Genome Projects
Mutations are changes in the nucleotide base sequence, and are quite common. Mutations can be caused by random chance, by chemicals or radiation, and most commonly are caused by reactive chemicals (free radicals) formed in the ordinary process of metabolism. Specific mutations are often seen in response to UV light or smoking. The DNA repair enzymes can repair most of these, others may escape repair and can result in abnormality, such as cancer. If the mutation occurs in the zygote, or reproductive (germ) cells, the new offspring may carry the mutation. Somatic mutations play a role in the development of most cancers, being a step in the process. Only some mutations actually cause harm, others may make no harm (see Fig. 1). This complex system is in delicate balance, and it only requires a defect in a single gene to disrupt this balance, the effect may sometimes be lethal. There are many new genes being discovered every week (For news of genes and genetic disease).
Figure 1: Mutations
alter Amino Acid Sequences
The original and the mutated DNA sequences may give rise to the same amino
acid, a different amino acid, or stop translation. A frameshift mutation
completely alters the amino acid sequence resulting in a nonsense message.
DNA Sequence Protein Sequence
Original
AACTAATTGCGTA Leu-Ile-Asp-Ala-
Neutral Mutation
AACTAGTTGCGTA Leu-Ile-Asp-Ala-
Single amino acid change
AACTACTTGCGTA Leu-Met-Asp-Ala-
Deletion, frameshift
AACT/ATTGCGTA Leu-Ile-Thr-His-
Insertion, frameshift
AACTAGATTGCGTA Leu-Ile-STOP
The cause of many genetic diseases is a simple nucleotide substitution, which occurs at a low frequency during the duplication of DNA. The effect of this nucleotide alteration is summarised in Fig 1. The effect does not always depend on the size of the deletion, but more on whether the resulting sequence has a shift in the reading frame for protein translation. This is summarised in Fig. 2. For example in patients with muscular dystrophy, part of a gene for a protein dystrophin is deleted. The severity of the disease depends on whether it is out of frame, rather than how much is missing. As long as some type of protein can be made the muscle cells may be able to function.
Figure 2: Effect
of frameshift mutation
Original
THIS LINE CAN BE READ WELL
Single letter deletion (frameshift)
THIS LINC ANB ER EADW ELL
Whole word deletion
THIS LINE BE READ WELL
There are also more major mutations, where large fragments of DNA can be translocated to a different chromosome. Abnormal chromosome numbers can also occur, so instead of two copies there may be three copies. Because this alters the number of alleles of genes for certain proteins, this can have major affects, usually resulting in death. Trisomy 21, where there are three copies of chromosome number 21 results in Down's syndrome, and is an example where death may not be the only result. In most other chromosome trisomies, death occurs during fetal growth, and/or spontaneous abortion.
Often only one of each pair of alleles of each gene is needed for normal
function. Some of the alleles may be so different in their sequence from the
normal that the protein or enzyme that they produce is nonfunctional. If this
is the case then the individual will use the functional allele of the pair and
this will normally allow a completely normal life, or phenotype. Sometimes one
of the alleles produces an abnormal but functional product; again the
individual will probably live normally. But if the individual possesses two
nonfunctional, or misfunctional alleles for any gene then the effect will be a
genetic disease. Normally the defective allele is not used if there is a
normal, functional alternative allele, and the allele would be called recessive because of this.
People may carry a recessive
disease-causing allele without it having any affect on them, but it is possible
that it will be passed on to their offspring. In some cases the defective
allele is dominant which means
even an individual with one normal and one defective gene will suffer from the
disease. Dominant and X-linked mutations often cause severe disease and
interfere with reproduction so would not last many generations. The recessive
mutations have the greatest chance of being maintained in the population, no
mutations would be eliminated in the first generation, as each individual would
only be a carrier, and if there is only one copy, then there is no effect. They
would be present for generations, and the most common mutation in cystic
fibrosis is thought to have originated about 50,000 years ago.
Q1: How many genetic diseases do you know? How many mutations do you
have? How many fatal recessive alleles do you carry in your genome?
Genetic disease is not usually
lethal and some abnormalities have little effect. About 3-4% of children suffer
from some type of genetic disease at birth. Every human possesses a specific
genotype, consisting of many units called genes; each gene directs the
manufacture in our body of a specific component, these components are usually
proteins of which the most important class for genetic studies are enzymes.
Every person has new mutations, and carry alleles which could cause disease. We
all carry about twenty recessive
alleles for lethal characteristics, but because these occur at low frequency the
incidence of a child being born with two recessive alleles is low. We all have
mutations, some are found in the reproductive cells and others in the body, or
somatic, cells. Both types of mutation have the potential to cause cancer.
5.2.1 Methods of Genetic Screening
DNA is normally found in double-stranded form (the double helix). The four
bases are given the symbols, A,T, G, and C. The base A binds with T, and the
base G binds with C, between these long chains, as is shown below:
---ATTCCGAAGCTGACTGA--- parent chain
---TAAGGCTTCGACTGACT--- complementary
DNA in the cell is normally found as a pair, it is more stable. To understand
genetic screening we do not need to know any more then the fact that these four
bases bind together, A to T, and C to G.
Genetic screening involves the use of this complementary binding. A sample of DNA is taken from a cell, and
then the DNA is split into single chains. The bases in this single-stranded DNA
will bind to the pairing bases. To make it easier to test, this single-stranded
DNA may be fixed to a plastic filter. We can test for the presence of a certain
sequence in this fixed DNA by adding a solution of single-stranded probe DNA, a
short sequence of synthetically made DNA with a label on it, like a fluorescent
dye. After mixing the probe with the sample the probe that is not bound to the
complementary sequence is washed away. If there are copies of the sequence in
the sample, we will be able to see the probe when we hold the filter under ultraviolet
light, because the probe is fluorescent. If there is no complementary sequence
in the sample to the probe, then we will not see any fluorescence.
In this way, many samples can be tested, with many probes, and this is
genetic screening. We screen for the presence or absence of particular DNA
sequences that represent different genes. This screening can be used to detect
a mutation, for example to say that a fetus has a mutation that will cause a
genetic disease (prenatal diagnosis). It can also be used to detect which type
of bacteria is present in a food sample, or for medical diagnosis of a patient.
The information about whether an individual has a particular DNA sequence
and gene, can be very powerful, especially in the diagnosis of genetic disease.
There are many ethical and legal issues that result from this technology. For
example, presymptomatic screening means
testing for a late-onset genetic disease, like Huntington's disease, before the
person is sick. It is predictive power that may need psychological counseling.
It is very important that privacy
is respected, because the information in a person's genes identifies some of
our risk to disease that medical insurance companies and employers could use to
discriminate people. There are already cases of discrimination of individuals
after genetic testing in North America.
Many genetic diseases (such as diabetes or cancer) are caused by the effects
of multiple genes, and the relationship between environment and genes. Genetic susceptibility means that a particular gene is only one
determinant for developing a complex disorder. For example to have an allele
called Apo E4 (that about 10% of Caucasians and Asians have) increases the risk
of developing Alzheimer's disease,
and it is a very strong susceptibility at younger age if you have two alleles,
whereas another allele for this gene, Apo E2, seems to be protective against
Alzheimer's.
Q2: Is there any advantage to have presymptomatic screening for
Alzheimer's disease when you are 20 years old? What about when you are 60 years
old?
5.2.2. Prenatal screening
Prenatal diagnosis or screening has become associated with normal prenatal
care in most industrialised countries. There are some important non-genetic
screening programmes. For example, if a woman is not immune to rubella, she
should be immunised before becoming pregnant. Recombinant DNA techniques were
first used for prenatal selection of sickle cell disease in 1982. However the
most general screening used today is based on protein screening because for
many diseases it is the lack of functional enzyme that is important, it may not
matter what allele you have as long as some protein can be made (see the
earlier example of PKU).
For a growing number of known genetic diseases, methods have been developed
to detect the genetic defect early in fetal life. These methods rely on
removing a sample from the fetal material and analysing it. There are different
stages at which fetuses can be screened for genetic disease or abnormalities.
As far as the ethics and the distress and the health risk to the mother are
concerned, the earlier the better.
Fetal sampling is laborious so that currently only a small proportion of the
population, can be screened even if it is considered desirable. Ultrasound is routinely used, and has the advantage of being
non-invasive. Different methods may be combined, for instance the first
screening may be maternal blood sampling, and if the level of certain proteins (e.g. alpha-fetoprotein) is
abnormal, there is greater risk that the fetus may have some problem such as
spina bifida or a chromosomal problem, like Down's syndrome. Then further
testing is needed to check the result of a blood protein test, as still in most
cases with an unusual protein level the fetus is normal.
Samples of placenta or fetal tissue may be taken from those fetuses
considered at high risk, i.e. those of older mothers or parents who have a
history of genetic disease. The older technique used is amniocentesis, where cells from the amniotic fluid are removed
and grown in the laboratory for analysis. No harm is done to the fetus as the
fetus is surrounded by discarded cells in the amniotic fluid which are no
longer needed for further growth. The fetal samples can be taken at 11-16 weeks.
It is now possible using very sensitive genetic probes to take a sample of the
chorionic villi (membranes around the fetus) at 6-9 weeks and analyse the fetal
DNA directly to determine whether it has a specific genetic defect, with the
technique of chorionic villi sampling. Like amniocentesis there is a 1-2% risk of miscarriage after the
sampling due to the procedure, which is why they are not general.
We are still unable economically, ethically, or socially, to screen every
fetus for so many diseases, with these techniques. Currently efforts and
resources are focused on parents with higher risk, however, the latest screening techniques allow hundreds of samples to
be tested with over a hundred different probes simultaneously, which allows low
cost routine screening, which could enter widespread use. There are mail order
companies in the UK that allow cystic fibrosis tests. In the future it will be
possible to routinely use the technique where the few fetal cells that can be
found in the mother's blood are isolated, and analysed. It is already possible
to use preimplantation diagnosis
to look at an embryo before implanting it in the mother, when IVF is used.
However, IVF is not an option for general use as medical resources are limited.
It may be an option for those parents who refuse abortion of a fetus, but have
a high risk of passing on a genetic disease.
5.2.3. Ethical issues
The general aim of prenatal diagnosis is to reassuremother's who are worried that their fetus has some
disease. They may avoid pregnancy without the possibility of such reassurance
that the fetus did not inherit some disease, or abort because they worried
about some ill effect from a drug used before the mother knew she was pregnant.
Prenatal diagnosis does not always mean an affected fetus will be aborted.
In fact, medically it should be separated. There are a number of advantages for
the parents who want to bear a child regardless of the fetus's condition. The
first is that some therapy may be
possible to solve the problem, or even to lessen the seriousness of the
condition. There are even cases of surgery being performed on a fetus and the
fetus being returned to the mother's womb. Another benefit is knowledge, to be
informed before birth and emotionally prepared.
Human procreation is associated with a high degree of error, because when
genetic elements rearrange there are often mistakes. The number of fertilised
embryos with genetic abnormalities may be about 70%. Most of the genetically
abnormal embryos are never implanted, or are spontaneously abort in early
pregnancy. But some babies are born and will die later, some have a painful
life others do not. If a fetus has a serious genetic impairment, with a
consequence of serious mental deficiency, some people might say that the fetus
does not, and will not in the future, have a "life" as
"normal" humans have a life, it's potentiality is different.
Do we deny the potential for spiritual relationship between God and the most
diseased forms of human life? Severely retarded individuals may never be
spiritually aware - but can we judge? Many religions would argue there are no
"worthless" lives. We should build a society to prevent
discrimination, and make life easier for those with disability, whether or not
we accept using prenatal screening.
Although we will retain division over the issue of prenatal genetic
screening, with some people continuing to reject it, ethically we need a system
to respect the informed choice of families. They must decide their
responsibility to present dependents and future children, and think firstly of
the children's quality of life. The correct decision is not to say do not abort or abort, but it may be
the decision made by the informed mother. Society may put limits on the extent
of this choice, e.g. maybe for sex selection, and maybe for fears of misuse.
Q3. Suppose a couple already has three girls, and they want a boy. Do you
think that the couple can use sex selection or even selective abortion to
increase the chance of having a baby boy?
To News on Genetic Screening and Ethics
5.3. Eugenics
The word eugenics was coined by Sir
Francis Galton and is derived from the Greek word "eugenes" which
means "good genes". Eugenics differs from other human activities in
that it is an activity in which we are trying to change ourselves, not the
environment or other creatures, and therefore is particularly challenging.
People have had ideas of selective breeding to increase the representation
of people with "good genes" for a long time. Plato considered the
desirability of achieving these ends by subtle, or direct, incentives to
control marriage, and/or mating, of supposedly 'fit' human beings. This is what
we could call positive eugenics, as opposed to negative eugenics which is reducing
the occurrence of genetically determined disease.
The "eugenicists" saw less children from the genetic
"stocks" of the more educated families, and worried that their
progeny would be swamped by large numbers of children from uneducated, and what
they mistakenly thought of as genetically unfit, classes. The peak of the
eugenics movement in the 1910-1920 saw the concept taught as a scientific
concept in biology textbooks, immigration laws to restrict "unfit"
immigrants, and compulsory sterilisation of women judged to be feeble-minded.
The Nazis in Germany took mainly US ideas and extended these to the extreme of
euthanasia of handicapped persons and the Holocaust and Racial Hygiene which
saw the mass murder of Jews, Slavs, Gypsies and other groups.
Beside many ethical objections to discrimination, a major scientific proof
against sterilisation being effective
eugenically was the Hardy-Weinberg Law, in 1908. The Hardy-Weinberg Law
explains in a scientific way why sterilisation would not work, and let us tyake
the example of Sickle Cell Anemia which is a disease found in many Africans.
The undesirable allele in this case is the one which causes the disease in the
homozygos state, which is generally fatal (though may now be particially
treated). So if you have two copies you will die, however if you carry one copy
you will have normal health and have an extra advantage that you can better
resist malaria. Therefore in parts of the world which have malaria, this allele
(and actually several other genes which cause recessive genetic disease which
is fatal), is more common because carriers survive better. We know now we all
carry about 15 different fatal recessive alleles, so under their sterilisation
logic no one should have children!
The key ethical issue is that while we all have responsibility to ensure the
health of future children, the choice to have children or not is one that
society has decided is individual. One of the fundamental human rights recognised in the International Conventions on
Human Rights is the right to found a family. There should be no social
restriction, rather we need to think of the individual child-to-be. To have a
disease is undesirable, so in the sense that to have a genetic disease is the
result of a "bad" gene it is a bad thing, and to have a normal
functional allele "a good gene" is good, but this criteria cannot be
used to stop people from having children.
Q4: What is a bad gene? What is a good gene? How different are others
perceptions of bad and good? How much desire could parents have for eye colour,
height, obesity, of their children?
DNA sequences can be used to identify individuals, and have been used for
legal cases. When the DNA is specifically cut up by restriction enzymes and the
pieces are separated unique patterns are made, called DNA fingerprints. They have been used for many court cases
world-wide, being more precise than blood-type matching. There have been
disputes about the probability of two individual's DNA fingerprints matching,
and calculations have recently been revised, but there is still a low
probability of such fingerprints matching (when the size of the fragments of
DNA made after digestion with the restriction enzymes, are the same in two
individuals).
In the USA a genetic register of criminals is being established by the FBI,
and there is also a police database in Britain. DNA fingerprints are also used
for immigration cases to prove genetic parenthood. Privacy is the key ethical
issue to protect individuals, and at least until we can guarantee privacy and
no abuse of the information, we should not establish larger genetic registers.
Many genetic diseases may be able to be treated
by correcting the defective genes, by gene therapy. Gene therapy is "a therapeutic
technique in which a functioning gene is inserted into the somatic cells of a
patient to correct an inborn genetic error or to provide a new function to the
cell". There have been many human gene therapy clinical trials, involving
over 700 patients world-wide (by 1996), for several different diseases
including several cancers. In the USA the trials must be approved by the
Recombinant DNA Advisory Committee (RAC) and the FDA. The RAC meetings are open
to the public, to help allay fears about genetic engineering.
It is still an experimental therapy, but if it
is safe and effective, it may prove to be a better approach to therapy than
many current therapies, because gene therapy cures the cause of the disease
rather than merely treating the symptoms of a disease. Also, many diseases are
still incurable by other means. One success already known is curing an
immunodeficiency disease, ADA deficiency, by allowing expression of the enzyme
made from a normal gene in the cells of children lacking it.
Currently such gene therapy is not inheritable,
we need to have much wider discussion about the ethics and social impact before
we start inheritable gene therapy. However, non-inheritable (somatic cell) gene
therapy to treat patients involves similar issues to any other therapy, and if
it is safer and more effective, it should be available.
Q5: Do you think there are any differences
between gene therapy and other therapy? Does any conventional therapy also
change DNA? When was the first trial of gene therapy in New Zealand?
Q6: What are the ethical differences between
inheritable and non-heritable gene therapy?