Showing posts with label Genetic engineering. Show all posts
Showing posts with label Genetic engineering. Show all posts

Human Genetic Engineering is a step too far

Below is from this source....

Human genetic engineering provokes strong reactions. Dr David King, director of Human Genetics Alert, recently warned: ‘In a world first, the Government has said it will allow scientists to begin developing the technology for genetic modification of human beings, although creation of actual GM babies will be prohibited for the moment. We believe the public will be horrified’ [Ref: Telegraph]. The government move comes in the context of an overhaul of legislation on assisted reproduction and embryology designed to take account of the latest scientific developments [Ref: Guardian]. The spectre of eugenics haunts the designer babies debate. As one journalist puts it, the idea of designer babies tends to prompt comparisons with the Nazis, the hatcheries in Aldous Huxley’s novel Brave New World and the biological underclass of the science fiction movie Gattaca [Ref: Times Online].

While there are real concerns about what the future might hold, the debate requires separating fact from science fiction. The argument of supporters of genetic engineering is that fears are often exaggerated. Rather than crossing a significant ethical threshold, they say we’ll benefit from a continued improvement in our ability to overcome disease and improve people’s lives. Deciding who is right first requires understanding what scientists are capable of doing today. Then future possibilities need to be assessed. Finally, we’ll be in a position to assess what poses the greatest danger: that we take a step too far or that we fail to take the necessary steps towards further scientific developments.

What IS genetic engineering?

Definition

noun

The technology entailing all processes of altering the genetic material of a cell to make it capable of performing the desired functions, such as producing novel substances.


Supplement

Genetic engineering covers all various experimental techniques that manipulate the genes of the organism. It uses recombinant DNA, molecular cloning and transformation. At present, it is applied in improving crop technology, manufacturing synthetic human insulin (using modified bacteria), production of erythropoietin (using Chinese hamster ovary cells), and production of new types of experimental mice for research (such as cancer mouse). It also has the potential of being used in humans by changing their appearance, intelligence, character and adaptability; however, there are ethical concerns and controversies it has to resolve before it can be widely accepted.

From the Web site of safe-food.org, genetic engineering is "a laboratory technique used by scientists to change the DNA of living organisms." Put another way, genetic engineering is "the alteration of genetic code using artificial means" (from www.globalchange.com). Genetic engineering is also called bio-engineering, gene-splicing, gene manipulation, etc. and the organisms that result from the practice are called genetically modified organisms (GMOs).

genetic engineering,

the process of producing recombinant DNA for the purposes of altering and controlling the genotype and phenotype of organisms. Restriction enzymes are used to break a DNA molecule into fragments so that genes from another organism can be inserted into the DNA. Genetic engineering has been used to produce a variety of human proteins, including growth hormone, insulin, and interferon, in bacteria. At present, it represents a powerful tool for medical research but is possible only in microorganisms. In the future, genetic engineering may be applicable to more complex organisms, offering the possibility of controlling and eliminating genetic disorders and malformations in humans.

Mosby's Medical Dictionary

YOUtube on genetic engineering....


Also....



Religion, genetics and the embryo

The source of this article is here...

Once upon a time Christian theologians argued about the sex of angels. Nowadays they argue about the soul of the human embryo in a debate that concerns creatures of flesh and blood and spills way beyond Christianity.
“Although religious practice may be declining,” says French geneticist and Member of Parliament Jean-François Mattei, “the metaphysical issue is still at the core of the questions raised about genetic engineering, either by tradition, culture or duty.”
Should a person have recourse to prenatal screening and consider having an abortion if a serious genetic defect is discovered? Should research on embryos, gene therapy and cloning be allowed?
All the “religions of the Book” (Christianity, Judaism and Islam) believe that the answers to these questions largely depend on the status of the embryo. The frontier between “good” and “bad” genetic engineering depends on whether or not the embryo is considered to be “animate”.

An “opposition front”
“If the embryo has a soul, then it is endowed with a human as well as a biological life and any attack on its integrity is seen as a crime,” says French geneticist René Frydman. “If it is inanimate, the prohibition remains—God-given life should be respected—but the offence is less serious.”
The Catholic Church is in many respects a special case. For a start, it has a single “magisterium” or teaching authority, whereas other religions have a more familiar approach, such as discussions with a rabbi (Jews), priest (Orthodox Christians) or master (Buddhists). Other religions also have various branches (reformed and orthodox Jews, many broad streams of Buddhism) or schools of jurisprudence (Malikite, Hanafite, Shafi’ite and Hanbalite among Sunni Muslims, for example). Most important of all, while all the major religions generally believe human life and dignity should be respected, the Church of Rome is the only religion that considers the embryo “as a human being from the moment of conception”, and it sticks firmly to this doctrine.
Pope John Paul II has repeated it several times, notably in the encyclicals Veritatis Splendor (1993) and Evangelium Vitae (1995). These have resulted in a number of prohibitions: “no” to prenatal screening if it it is done with the thought of a possible abortion and “no” to most research and therapy on embryos. The Vatican is also against both reproductive and therapeutic cloning on the grounds that it violates the “unified totality” of the human person and the sacred link between sexuality and procreation.
The positions of Orthodox Christians are very close to those of the Vatican. But the “opposition front” to genetic technologies is limited to these two groups. For Islam and Judaism, the important principles are the moment when the embryo acquires a life of its own and respect for descendance. The Koran says in Surat 23: “And certainly We created man of an extract of clay, Then We made him a small seed in a firm resting-place, Then we made the seed a clot, then we made the clot a lump of flesh, then We made (in) the lump of flesh bones, then We clothed the bones with flesh, then We caused it to grow into another creation.”
But some Muslims believe it is 40 days before the soul (ruh) enters the embryo, while others believe it is 120. At the same time, while prenatal screening is accepted, there is argument over abortion. H’mida Ennaifer, of the Higher Institute of Theology in Tunis, says “Islamic jurists all condemn abortion after the foetus has received the breath of life. Some Malekites condemn it even when the child is less than 40 days old while other schools of thought allow it during the first four months of pregnancy.”
Islam also allows gene therapy on the human body, but in general it proscribes the modification of germ-cells and bans anything which denies the notion of divine creation, starting with cloning. However, a minority of jurists regard cloning as sometimes preferable to “genetic adultery” because it respects the line of descent by avoiding a situation where a sterile couple uses sperm or eggs from a donor in artificial insemination.
Jews cite the Bible and the Talmud. When the Talmud reports that during the miraculous crossing of the Red Sea by the Israelites (Exodus, chapter 15), even the unborn children in their mothers’ wombs praised God, it comments that “if they could praise the glory of God, it means they have a soul and a conscience.” This comes about after the 40th day, the Talmud says. Until then, the embryo is “only water”. So to obey the halakha (Jewish Law), it is preferable to carry out prenatal screening before the 40th day. After that, abortion is not allowed unless the mother’s life is in danger. In practice, it all depends on what the rabbis say. Some hold that if the mother has a nervous breakdown when she learns she is carrying a child with an incurable condition, abortion is permissible, even after the 40-day limit. Other rabbis are a lot stricter.
Jews allow experiments with embryos, especially if they have no chance of surviving. Judaism also does not rule out cloning, says French theologian and jurist Raphaël Braï. “If cloning is done for therapeutic reasons, the matter has to be discussed with other people. Several religious notions clash at this point. For example, the oneness of the human person and the duty to heal oneself.” But cloning for reproductive reasons is not allowed, with few exceptions.
Protestant Christians are generally even more open to advances in genetics. They stress free will and regard each case on its merits, leaving a decision to the couple involved. “Some allow prenatal screening followed by an abortion if the woman so decides,” says Carlos de Sola, head of the bioethics unit of the Council of Europe, which has arranged discussions between religious authorities. “Some people even endorse choosing the sex of a future child through sperm selection, so as to create a family containing both boys and girls.” Protestants approve of research using embryos as long as it is strictly supervised. They do not rule out cloning either, though they reject cloning for profit or for eugenic reasons.
Buddhists are even less dogmatic because they believe all truth is relative. A French expert in Buddhism, Raphaël Liogier, notes that “the only ethical limit is suffering, for Buddha is primarily a healer.” The Dalai Lama, leader of Tibet’s Buddhists, says what mainly has to be taken into account are “the good effects and bad effects of genetic engineering.” He agrees that it can be used to “improve the human body—the brain, for example.”
“The body is only a vehicle for karma [the ethical consequences of a person’s actions that determine their destiny in their next incarnation],” says Liogier. “If the body has been genetically altered or cloned, it’s really not very important. Abortion however is frowned on because it damages karma.”
But again, everything is relative and the main concern is to avoid pain. The Dalai Lama says “abortion is allowed when a pregnant woman might die if she gave birth or bear a severely handicapped child.”
The range of answers religions give to bioethical questions is very varied and constantly changing, except for the rigid doctrine of the Vatican and the inflexibility of fundamentalists in all religions. Faced with problems which go to the origin and meaning of life itself, says Frydman, “religious opinions are probably a big help because they recall humanity’s root values without trying to impose them and are a forum for discussion, not a body of dogma.”


Christianity and genetic engineering

Because genetic engineering was unknown at the time that the Bible was written, it is difficult to establish definitive references on that topic alone. In order to determine the Christian view of genetic engineering, we need to establish a grid of principles through which to view genetic engineering. For specifics on the Christian view of cloning please see “What is the Christian view of cloning?

The element of greatest concern about the issue of genetic engineering involves how much liberty mankind can take in its responsibility to care for the human body and the rest of creation. There is no doubt that the Bible exhorts us to be responsible for our physical health. Proverbs refers to certain activities regarding restoring the health of an individual (Proverbs 12:18). The Apostle Paul states that we have a certain duty to care for the body (Ephesians 5:29). He also encouraged his protégé, Timothy, to take medicinal action for his infirmities (1 Timothy 5:23). We are also aware that believers have the distinct responsibility of responding properly with the body in that it is the temple of the Holy Spirit (1 Corinthians 6:19,20). We are to show our faith by offering assistance to those who have physical needs (James 2:16). Therefore, we can conclude that as Christians we should be concerned about physical well-being and the benefits of securing help with our health.

Second, the creation was to be under the care of humans (Genesis 1:28; 2:15-20), but the Bible tells us that creation was impacted by the sin of humans (Genesis 3:17-19, Romans 8:19-21) and anticipates being redeemed from its effects. It is possible to conclude that as caretakers for the creation, humans have an obligation to “fix” the effects of the sin curse and attempt to bring things into a better alignment, using any means possible. Therefore, the thinking goes, scientific advances could be used for the betterment of the creation. However, there are concerns regarding employing genetic engineering to accomplish this good.

1. There is the concern that genetic engineering will take on a role beyond what God has given to us as His creation. The Bible states that all things were created by God and for Him (Colossians 1:16). As individuals we are made in God’s image and therefore should be subject to His plan (Genesis 1:26,27; Matthew 22:20,21). God designed all living things after certain “kinds” (Genesis 1:11-25). Too much manipulation of the genetics (altering species) could be delving into issues reserved for the Designer.

2. There is the concern of genetic engineering attempting to preclude God’s plan for the restoration of creation. As stated above, the creation was affected by the events recorded in Genesis 3 (mankind’s rebellion against God’s plan). Death entered into the world, and man’s genetic make-up and that of the rest of creation began a change toward demise. In some instances, genetic engineering could be seen as an attempt to undo this result called the “curse.” However, God has said that He has a remedy for this—redemption through Jesus Christ, as described in Romans 8 and 1 Corinthians 15. The creation anticipates newness associated with the culmination of God’s promise to restore things to an even better state than the original. To go “too far” to fight this process may compete with the responsibility of individuals to trust in Christ for restoration (Philippians 3:21).

3. It seems evident from general scriptural study that God has a plan for the process of life. It seems evident that the process is unique and purposeful. There is concern that if humanity interferes with that process, something could go terribly wrong. For example, Psalm 139 describes an intimate relationship between the psalmist and his Creator from the womb. Would the use of genetic manipulation to create life outside of God’s plan jeopardize the development of a God-conscious soul? Would interfering with the process of physical life affect the prospects of spiritual life? Romans 5:12 tells us that all humanity sins because Adam sinned. It is understood that this involved the transference of the sin nature from generation to generation so that all have sinned (Romans 3:23). Paul explains the hope of eternity through the conquering of Adam’s sin. If all that are in Adam (from his seed) die, and Christ died for those in such condition, could life created outside of that “seed” be redeemed? (1 Corinthians 15:22, 23).

4. There is also the concern that such bold strides in genetic engineering are motivated by a defiance of God. Genesis 11:1-9 discusses what happens when the creation attempts to exalt itself above the Creator. The people in Genesis 11 were unified, yet they were not submissive to God’s design. As a result, God stopped their progress. God certainly recognized that there were some dangers involved with the direction in which the people were headed. We have a similar warning in Romans 1:18-32. There God describes individuals that have become so enamored with the creation (actually worshipping it rather than the Creator) that those individuals spiraled down to destruction. There is a danger that genetic engineering could foster similar motivations, and ultimately, similar results.

These are questions and issues for which we have no answers at present, but they are concerns, which should be carefully considered by Christians attempting to adopt a view of genetic engineering.

Islam and genetic engineering

Responding to the topic of genetic engioneering, the eminent Muslim scholar, Sheikh Yusuf Al-Qaradawi, states the following: One of the blessings of Islam is that it never abstracts scientific programs or narrows the scope of the mind in the field of science and technology. Unlike other religions, there is no conflict between science and religion in Islam. Christian clergy opposed scientists, thinkers and pioneers of technology that we take for granted today. Many were punished, tortured and sentenced to death.

The Qur’an shows that Allah, Almighty, bestows many gifts on mankind enabling them to discover the mysterious nature around them and to recognize the laws that control the universe. Allah Almighty also submits the whole universe with its heavens, earth, sun and moon to mankind.

Allah Almighty says: (See ye not how Allah hath made serviceable unto you whatsoever is in the skies and whatsoever is in the earth and hath loaded you with His favors both without and within? Yet of mankind is he who disputeth concerning Allah, without knowledge or guidance or a Scripture giving light.) (Luqman 31: 20)

He Almighty also says, (And in the earth are portents for those whose faith is sure. And (also) in yourselves. Can ye then not see??w (Adh-dhariat 51: 20-21)

When man’s knowledge advances, it becomes compulsory for him to deepen his faith and moral virtues. One must not go alone, doing whatever one wants, ignoring religious morals or the welfare of people in general.

The problem in Western civilization is that science is separated from religion and in some cases it fights religion.

Allah Almighty says, (And when he turneth away (from thee) his effort in the land is to make mischief therein and to destroy the crops and the cattle; and Allah loveth not mischief.) (Al-Baqarah 2: 205)

We welcome the idea of genetic engineering. It is one of the greatest discoveries of our time and is shared by many countries. Whether it is considered more important than the discovery of penicillin or man landing on the moon, we hope it is used for the benefit of humanity and that its guidelines will be according to the views of qualified jurists.

There are many benefits we can derive from this, say, for instance, in treating genetic diseases by using the effective genes to prevent harm or disease. This is something commendable in Islam according to the legal rule "Prevention is better than cure"; the rule is taken from the hadith; “There should be neither harm nor reciprocating injury.”

By this, through the assistance of such a scientific device, man will be able to prevent many diseases.

Questions

  • Is it ok to choose embryos because they have been screened for a cancer gene?
  • What about choosing an embryo based on gender?
  • If a gene can be found for homosexuality, is it ok to screen for that?
The source for the following is here

How far is too far when it comes to genetic engineering? The question became a lot more relevant this morning, when it was announced that the world's first "cancer free" baby was born in England. A spokesman for the University College London told CNN that the child was tested as an embryo for the BRCA-1 gene, which has been linked to breast and ovarian cancer.

People with the BRCA-1 gene have been found to have a 50-80% chance of developing breast or ovarian cancer in their lifetimes. The child may still develop non-genetic forms of cancer, however.

"The parents will have been spared the risk of inflicting this disease on their daughter. The lasting legacy is the eradication of the transmission of this form of cancer that has blighted these families for generations," said Paul Serhal, a consultant at University College London Hospital and Medical Director of the Assisted Conception Unit.

Choosing a "cancer free" embryo does not sit well with everyone. Josephine Quintavalle, co-founder of Comment on Reproductive Ethics, is upset that the three day old embryos are destroyed if they are found to be carrying a genetic deficiency. She stated, "This is simply a mechanism for eliminating the birth of anybody (prone to) the disease. It is basically a search-and-kill mechanism." Comment on Reproductive Ethics deals with ethical dilemmas related to reproduction.

On the other side is Peter Braude, a top expert on genetic testing of embryos in England. He argues that discarding three day old embryos that have not been implanted will prevent abortions. "There has always been a vociferous group in opposition," he said. But "there are people who can benefit and I think they should be allowed to do so."

Choosing children

Choosing children - the ethical dillemmas of genetic intervention....worth a read...

Susan Aldridge wrote the below

What are the pxincipal ethical issues created by modern biology?

The major ethical issues arising from recent advances in biological science are:

  1. Human embryo research
  2. The misuse of genetic screening
  3. The release of genetically engineered microbes, plants and animals into the environment
  4. The modification of genes in the human germ-line

We will consider each of these issues in tum.

Human embryo research has been the subject of extensive debate for some years. In some countries it is prohibited, in others it is not. The main problem is due to the lack of consensus on a basic human question: when does a fertilized human egg become a human being? This is a fundamental ethical question because a human being has human rights, including the right-tolife. 'Me Catholic Church and many other religious groups strongly oppose abortion. For them life starts from the fertilized egg, so abortion is murder, and for people with these beliefs, human embryo research is absolutely unacceptable. The USA is a country which since 1973 has had liberal abortion laws. The Supreme Court, in the case of Roe vs. Wade, ruled in 1973 that any woman has an unrestricted right to abort a foetus during the first 3 months of pregnancy. There are about 1.5 million legal abortions carried out in the USA each year. This being so, why should not some of these millions of aborted foetuses be used for research, instead of being incinerated? Such is indeed allowed in the USA, but other countries do not allow such research. This is, however, an ethical problem, to which scientific knowledge has little relevance. Biologically, there is nothing more special about a fertilized egg than an unfertilized one. Life is a continuum.

Genetic screening is an issue that will continue to be discussed for many years to come. Points of issue include whether genetic screening of embryos should be permitted. This procedure allows the detection of a defective gene in an embryo. In many countries there is already a widespread programme to screen for the chromosome abnormality that leads to Down's syndrome. Gene technology will allow many more conditions to be screened. Ethical problems are also raised by the genetic screening of new-bom babies. In some states of the USA, including Pennsylvania, every child bom is screened for a battery of diseases including Duchenne muscular dystrophy, a disease which leads to death before the twenties and for which there is no cure known. We think that this is a very dangerous practice not only because it can distress parents who have not asked to know the future of their children, but also because these genetic data have the potential to be misused by insurance companies and employers. This knowledge may stigmatize and marginalize people who had the bad luck to have a defective gene. In a human society, which so often mistrusts those who are different, a genetic passport can be a huge handicap. Perhaps President Lincoln would never have been elected, if' his political adversaries could have publicized the fact that he had the 'bad' gene which causes the Marfan syndrome, a condition caused by the possession of a dominant autosomal gene which results in ocular, skeletal and cardiovascular abnormalities. On the other hand, some genetic tests like that for phenylketonuria (see Chapter 10) need to be carried out because there is an effective treatment which prevents its deleterious etyects. We think, like several eminent human geneticists, that mandatory genetic tests should be allowed only in those cases where the genetic disease can be cured. The third problem arises from the genetic screening of adults. Such tests should never be mandatory, but only carried out with the consent of the individual, and even then the results should be kept secret. This is the only way to ensure that there is no discrimination against the carrier of'defective genes.

The release of genetically engineered organisms into the environment could cause unexpected environmental problems. We need to realize that it is possible to make combinations of genes in organisms in a way that would be impossible by natural selection. How do we decide it' a transformed organism might upset the balance of ecology in a particulaienvironment? Could for example, a bacteria, genetically engineered to eat oil spilled in the sea, in a few years become a fish pathogen? Might the pathogenicity start slowly, like the eftect of DDT, and then build up to cause a catastrophe? The second aspect of the release of genetically engineered organisms that has to be appreciated is that they are alive. In the case of chemicals which are found to have undesirable effects, it is possible to stop their use. Living organisms can reproduce themselves so stopping their use may not help. The only transformed organisms which should not be a threat are ones which require human help to survive. We do not know if all the thousands of organisms which have already been transformed have this peculiarity. The business of transforming genomes is exploding so rapidly that we do not have an overview of the problem.

The last issue is the biggest of all. Should we try to change or add genes in the human germ line, the cells in our bodies that have the potential to make gametes? Changes to the germ line therefore have the potential to be inherited. We should make it clear that it is not yet possible, mainly for technical reasons, to transform human germ cells genetically. But what is not possible today can be possible next year or in 5 years. Predictions are very difficult to make in science. Therefore it is necessary to discuss this problem now. Many gene therapists believe that the best gene therapy is not one which modifies somatic cells but that, if it is technically possible, it would be better to modify the germ line. Genetically speaking this may be correct, although many of the defective genes which affect humans arise as a result of new mutations and so 'cueing' humans of mutant genes will not be as easy as might be thought. Many people fear that once a technique for modifying the germ line to treat genetic disease has been introduced, it will slowly start being used for other things. It is not immoral to have children with brown eyes so why can we not introduce the gene which makes eyes brown? Or inactivate a gene or two so that a girl had fair hair. Why not introduce a gene which makes a boy 10 centimetres (4 inches) taller? To be resistant to alcohol would be a good thing, let us add that gene too. And what about the genes of intelligence, of courage, of sport achievement, resistance to asbestos, the gene of happiness? Do we want to change humankind? Who can decide which genes a future human being should have, the mother or the parents or the state or a committee of experts? Our new-found genetic knowledge raises questions for all of us that are so novel and fundamental that it is extremely difficult to know how the problem should be solved. Certainly, committees of experts are important to give advice but they should not make political decisions. There is also the problem that many prominent scientists are strongly involved in the biotechnology industry, and so their opinions may be biased. The medical profession is not a guardian of morals and even less a political institution. There are examples where the medical profession in some countries at some times has failed to uphold high moral values. Too many German doctors were willing to be involved in the Nazi eugenics programme. Less well known is the fact that the American Psychiatric Association until 1974, classified homosexuality as a mental disease. The initiation of a programme that allows the genetic modification of the human germ line, even for the purposes of gene therapy, needs widely based and open discussion. The decision cannot be delegated to experts or to the medical profession. It is a political problem, but should it be left to politicians? Some issues are too big to be left to people who are often more concemed with re-election than with the future of society. Perhaps such important ethical issues should be decided by direct democracy. Should we use a Swiss style general referendum to decide on such an issue? The great advantage of this form of direct democracy is that everybody can participate in the public discussion for months before the referendum is held. The other advantage is that no one can say that she/he has no power in the matter. But would it ever be possible for the majority of people to be sufficiently informed to be able to vote rationally? There are after all many examples in history of the tyranny of the majority. Perhaps it is time for a novel form of democracy, in which decisions are taken only by those who can successfully complete a questionnaire that will test their background knowledge! We end with another quotation from the Bible:

The Lord God ... said, 'The man has become one of us, knowing good and evil; what if he now reaches out and takes fruit from the tree of life also, and eats it and lives for ever?' So the Lord God banished him from the garden of Eden to till the ground ... and he stationed the cherubim and a sword whirling and flashing to guard the way to the tree of life. (GENESIS, 3: 22-24)

We must all now decide whether, having eaten the fruit of the tree of knowledge, we wish to return to the Garden of Eden to take fruit from the tree of life, changing human genes in the hope of living for ever.

Tomorrow's Child Engineering the Human Germ-line Sharon Begley NZ Herald Nov 98

"Life would enter a new phase" says biophysicist Gregory Stock - "one in which we seize control of our own evolution".

IT IS only a matter of time. One day - a day probably no more distant than the fhst wedding anniversary of a couple who are now teenage ethearts - a man and a woman will walk mto an in-vitro fertilisation clinic and make scientific history. Their problem won't be infertility - the reason couples choose IVF now. Rather, they will be desperate for a very special child, a child who will elude a family curse. To create their dream-child, doctors will fertilise a few of the woman's eggs with her husband's sperm as as IVF clinics do today. But they will inject an artificial human chromosome, carrying made-to-order genes like pearls on a string into the fertilized egg. One of the genes will carry instructions ordering cells to commit suicide. Then the doctors the place the embryo into the mother's uterus. Left without the artifical genes if her baby is a boy, when he became an old man he, like his father and grandfather before him, would develop prostate cancer. But the suicide gene will make his prostate cells self-destruct. The man, unlike his ancestors will not die of the cancer. And since the gene that the doctors give him will copy itself into every cell of his body, including his sperm, his sonstoo will beat prostate cancer. Genetic engineers are preparing to what has long been an ethical Rubicon. Since 1990, gene therapy has meant slipping a healthy gene into the cells of one organ of a patient suffering from a genetic disease Soon, it may mean something much more momentous: altering a fertilized egg so that genes in all of a person's cells, including eggs or sperm also carry a gene that scientists, not parents, bequeathed them. When the pioneers of gene therapy first requested Government approval ,for their experiments in 1987, they vowed they would never alter patients eggs or sperm. That was then. This is now. One of those pioneers, Dr W. French Anderson of the University of Southern California,- recently put the National Institutes of Health on notice. Within two or three years, he said, he would ask approval to use gene therapy on a foetus which has been diagnosed with a deadly inherited disease.

The therapy would cure the foetus, before it was born. But the introduced genes, though targeted at only blood or immune-system cells, might inadvertently slip into the child's egg, (or sperm) cells, too. If that happens, the genetic change would effect the children to the nth generation.- "Life would enter a new phase," says biophysicist Gregory Stock of UCLA "one in which we seize control of our own evolution." Judging by the 70 pages of public comments the national instutes have received since Anderson submitted his proposal in September, the overwhelming majority of scientists and ethicists oppose gene therapy that changes the germ line (eggs and sperm). But the opposition could be boulevard wide and paper thin. "There is a great divide in the bioethics over whether we' should open this Pandora's box says science-policy scholar Sheldon Krimsky of Tufts University.

Many bioethicists are sympathetic about using germline therapy to shield a child from a family disposition to cancer or atherosclerosis or other illnesses with a strong genetic component.'

As James Watson president of the Cold Spring Harbor Laboratory and and co-discoverer of the double-helical structure of DNA said at a recent UCLA, conference . We might as well do what we finally can to take the threat of Alzheimers or cancer away from a family."

But something else is suddenly making it OK to discuss the once forbidden possibility Of germline engineering. Molecular biologists now think they have clever ways to circumvent the ethical concerns that engulf this sci-fi idea.

There may be ways for instance to design a baby's genes without violating the principle of informed consent. This is the belief that no one's genes, not even an embryos - should be altered without his or her permission.

Presumably a few people would object to being spared a fatal disease. But what about genes for personality traits, such as risk-taking or being neurotic?

But the child of tomorrow might have the final word about is genes says UCLA geneticistJohn Campbell. The designer gene for say patience could be paired with an of-off switch, he says. The child would have to take a drug to activate the patience gene. Free to accept or reject the drug, he retains informed consent over his endowment.

There may also be ways to make an end run around the worry that it is wrong to monkey with human evolution. Researchers are experimenting with tricks to make the introduced gene self-destruct in cells that become eggs or sperm. That would confine the tinkering to one generation. Then if it became clear that eliminating the genes for say mental illness also erased genes for creativity that loss would not also become part of the man's genetic blueprint.

In experiments with animals Mario Capecchi if the University of Utah has designed a string of genes flanked by the molecular version of scissors. The scissors are activated by an enxyme that would be made only in cells that become eggs or sperm. Once activated the genetic scissors snip out the introduced gene and presto it is not passed along to future generations. What I worry about says Capecchi is that if we start mucking around with eggs and sperm at some point - since this is a human enterprise - we are going to make a mistake. You want a way to undo that mistake. And since what may seem terrific now may seem naive in 20 years you want a way to make genetic change reversible.

There is no easy technological fix ofr another ethical worry however. With germ-line engineering only society's haves will control their genetic traits. It isn't hard to forsee a time like that painted in last year's film Gattaca where only the wealthy can afford to genetically engineer their children with such 'killer applications' as intelligence, beauty, long-life and health. "If you are going to disadvantage even further those who are already disadvantaged" says bioethicist Ruth Macklin of Albert Einstein College of Medicine "then that does raise serious concerns".

But perhaps is not enough to keep designer babies solely in Holywood's imagination. For one thing genetic therapy as done today (treating one organ per child or adult) has been a bitter disappointment. "With the exception of a few anecdotal cases" says USCs Anderson "there is no evidence of a gene therapy protocol that helps". But germ-line therapy might be easier to make effective. Doctors would not have to insinuate the new gene into millions of lung cells in say a cystic fibrosis patient. They could manipulate only a single cell - the fertilized egg - and still have the gene reach every of the person who develops from that egg.

How soon might we design our children? The necessary pieces are quickly falling into place. The first artificial chromosome was created last year.

By 2003 the human genome project will have decoded all 3 billion letters that spell out our 70,000 or so genes Animal experiments designed to show that the process will not create horrible mutants are under way.

No law prohibits germ-line engineering.

Although the National Institutes of Health now refuse to even consider funding for it, the rules are being updated And where there is a way there will almost certainly be a will.

"None of us" says Anderson "want to pass on to our children lethal genes if we can prevent it. - that's what is going to drive this."

At the UCLA symposium on germ-line engineering, two thirds of the audience supported it. Few would argue against using the technique to eradicate a disease that has plagued a family for generations. As Krimsky says "We know where to start" The harder question is do we know where to stop?

Evolution Extinguished NS 3 Oct 98 25

IF YOU put your ear to the tracks, you can hear the train coming. In conference halls around the world, geneticists and developmental biologists have been gathering to discuss what once was unthinkable-genetically engineering human embryos so that they, and their children, and their children's children, are irrevocably changed. These experts are talking with remarkable candour about using germ-line engineering to cure fatal diseases or even to create designer babies that will be stronger, smarter, or more resistant to infections. Doctors are already experimenting with gene therapy, in which a relatively small number of cells-in the lungs, say-are altered to correct a disease. Germ-line engineering, however, would change every cell in the body. People would no longer have to make do with haphazard combinations of their parent's genes. Instead, genetic engineers could eliminate defective genes, change existing ones or even add a few extra. Humanity would, in effect, take control of its own evolution. So awesome is this idea, that until a year or so ago, the taboo on human germline engineering was absolute. But opinions have started to shift. Once barely considered a topic for polite conversation among even the most gung-ho of geiieticists, germ-line engineering of humans is becoming so much grist to the mill of scientists gossiping around the coffee pot. Not that the pillars of the scientific establishment agree on this emerging technology, not by a long way. In a straw poll, researchers variously described the idea of human germ-line engineering as "irresistible", "morally questionable" or just plain "dangerous". What they did agree on is that germ-line engineered humans are likely to beconic a reality. Tampering with a human embryo to create that can be passed from one to the next is still more or less verboten 23 countries have signed a Council of Europe convention that bans it and officials at the US Food and Drug Administration promise not to give the go ahead without much public deliberation. Despite this however, most experts say they would be surprised if designer babies are not toddling around within the next 20 years or so. Gregory Stock, a biophysicist-turned- expert on technology and society at the University of California, Los Angeles, helped to organise a symposium in Marchcalled "Engineering the Human Germ- line". The task? Not to look way into the future, but at what we'll be faced with in the next decade or two. "There is no way to avoid this technology," explains Stock, who thinks that calling the evolutionary shots will create a happier, healthier society. "The knowledge is coming too fast, and the possibilities are too exciting." Public enthusiasm could soon match Stock's: poll after poll shows that a sizeable minority of paretits-sometitmes as many as 20 per cent-say tilat they see nothing wrong with genetically altering their children for health reasons, to give them an edge over the child at the next desk-or even to stop them being homosexual. So what is shifting the mind-set about human germ-line engineering from "never" to "well, maybe"? The inain driving force, most experts agree, is the new technologies rolling inexorably along the tracks. We are discovering not ony what our genes do, but how to make precise changes in themi Aild although the human genome isn't yet collipletely sequenced, already the ditabases contain details of thousands of genes, and of thousands of variations within them, along with information about how these variations affect physical and emotional traits. Added incentive comes, paradoxically, from frustrations with gene therapy. Gene therapy promised to cure genetic disorders such as cystic fibrosis and sickle-cell anaemia, and even common illnesses such as cancer. But although the glitches are slowly being fixed, few people have so far benefited from the procedure. The problem is getting new genes into enough cells, and keeping them there for long enough to do any good. With germ-line engineering you have to tweak only one cell-a fertilised human egg-which is "infinitely easier", says Leroy Hood, a molecular biologist at the University of Washington in Seattle. "We have terrific ways to do that." Once a genetic engineer has changed the genome of an egg fertilised in a lab dish, the egg divides over and over again, forming all the tissues of the body. Every cell will have exactly the same genetic make-up as the altered egg.

Now and forever

Genetically engineered mice and farm animals have been around for years and are used for everything from basic research to attempts to create "humanised" animal organs for transplant. But what might be considered a bonus in agricultural biotechnology-the fact that any changes are present in the animal's sperm and eggs (the "germ cells") and so will be passed on to succeeding generations-is for many the most worrying thing about genetic engineering in humans. The critics point out that if medicine has played a bit part in our recent evolution-antibiotics, for example, allow people with less than robUSt immune systems to survive long enough to pass this trait into the next generation-genetic engineering has the potential to be a star performer. One reason for cold feet is that large scale genetic engineering could actually rob society of desirable traits. What if the "disease" genes in combination with other genes, or in people who are merely carri ers, also help produce such intangibles as artistic creativity or a razor-sharp wit or the ability to wiggle ones ears? Wipe out the gene, and you risk losing those traits too. And while no one would wish manic depression on anyone, society might be the poorer without the inventiveness that many psychologists believe is part and par cel of the disorder. in his book Remaking Eden, Lee Silver, a biologist at Princeton University, goes as far as to suggest that a century or two of widespread engineering might even create a new species of human, no longer willing or able to mate with its "gene poor" relations ("Us and them", New Scientist, 9 May, p 36). "The potential power of genetic engineering is far greater than that of splitting the atom, and it could be every bit as dangerous to society," says Liebe Cavalieri, a molecular biologist at the State University of New York in Purchase. Cavalieri, who has worked in the field for more than 30 years, thinks it unlikely that the ugly side of genetic engineering will stop development of the technology in its tracks. "It is virtually inevitable it will get used and for the most banal reasons possible-to make some money, or to satisfy the virtuoso scientists who created the technology." If esoteric worries about what may or may not happen in a genetically engineered society are unlikely to change people's views, safety issues could-at least until they are solved. "There is a real risk of unforeseen, unpredictable problems," says Nelson Wivel, deputy director of the Institute for Human Gene Therapy at the University of Pennsylvania, and former executive director of the National Institutes of Health Recombinant DNA Advisory Committee. In gene therapy, genes are ferried into cells by modified viruses or other means. It's a risky business, because genes can get inserted in the wrong spot in the genome, killing the cell outright or, far worse, triggering cancer. But at least with gene therapy there is natural damage control-few cells pick up the genes even when the procedure goes well, cancer only affects one individual, and, as the procedure has always been carried out long after birth, there's no chance of upsetting key developmental genes. With germ-line engineering, on the other hand, there's more scope for unpredictable, even monstrous, alterations. Take the so-called "Beitsville pig". This pig, a thom in the side of high-tech agriculturists and an icon for animal rights activists everywhere, was engineered by scientists at the US Department of Agriculture to produce human growth hormone that would make it grow faster and leaner. The engineers added a genetic switch that should have turned on the growth hormone gene only when the pig ate food laced with zinc. But the switch failed. The extra growth hormone made the pig grow faster, but it also suffered severe bone and joint problems and was bug-eyed to boot. Of course, unlike human experiments, slaughtering "failures" is always an option for animal genetic engineers. Before genetic engineering of humans can become a reality, each candidate gene and its switches would need to be extensively studied in animals first, and any changes would have to be made with a surgical precision that reduced the chances of a "Beltsville human" to just about zero. As it happens, over the past few years, molecular geneticists have been busily developing the tools to do just this sort of "genetic surgery". For years, genetic engineers have altered farm animals by injecting genes into fertilised eggs and then placing them in an animal's womb. But the technique is far too unreliable to use in humans. Out of every 10 000 eggs injected, roughly three make it to adulthood with the gene functioning as planned. What's more, it is possible only to add whole genes, not to fine-tune existing ones. With mice, the process is more refined. Mice embryos contain embryonic stem (ES) cells that will grow and divide in a flask. That allows the engineers to make use of "homologous recombination", the process by which DNA strands bind to, and sometimes replace, DNA strands of similar sequence. With homologous recombination it is possible to make tiny, surgically precise changes within genes, with the technique depending in part on being able to sort through a large number of ES cells, only picking out the ones that have taken the genetic change in the correct place. Those cells are then added back to an embryo, where they can form any part of the animal. The result is a "chimera", an animal whose body contains both normal and altered cells. To create an animal with the altered gene in every cell, a chimera with the change in its eggs is bred with one that has the change in its sperm-one reason the technique can't be used in humans. But the efficiency of gene surgery is improving so that fewer cells are needed to start with. That has made it possible for several labs to try gene surgery directly on fertilised mouse eggs, says Dieter Gruenert, a molecular geneticist at the University of California, San Francisco, who is developing just such a technique. The process is still in its infancy, but it could one day make it possible to genetically engineer human eggs, eliminating the need for crossbreeding. A more immediate solution will probably come from an alternative way of generating lots of identical embryonic cells: the technology that produced Dolly & Co. Cloning relies on a combination of two new techniques. First, grow cells taken from an adult or an embryo in a flask under conditions that encourage them to divide and increase their numbers, and then trick them into reverting to a nonspecialised state with the potential to form an entirely new individual. Second, fuse one of these cells with an egg from which the nucleus has been removed, and implant this cutand-paste embryo into a womb. The wrinkles still need ironing out, but these techniques promise engineers the luxury of an inexhaustible supply of cells to attempt genetic surgery upon, only transferring to an egg those nuclei they know have been properly changed. And unlike the mouse ES cells, these cells will generate an animal with the genetic change in every cell. Born last year, Polly, a sheep with a gene for a human clotting factor, was created in just this manner.

Batteries of genes

With the exception, perhaps, of Richard Seed-the Chicago physicist who in January said he would open a human cloning clinic-no one is openly attempting to develop cloning for humans. But hundreds of genetic engineers are working to perfect its use in other mammals, including primates. "None of the technologies [that will allow human engineering] is being developed only for that purpose, but when you put them all together, that is what you will have," says Wivel. Even so, whether or not it is combined with cloning technology, "gene surgery" lets would-be human engineers go only so far. They could tweak a gene here or add one there, but they couldn't do much about characteristics such as intelligence, say, or disease resistance, or athleticism, which are under the control of numerous genes working in concert. For this, you'll need a budding technology that could soon make it possible to add whole batteries of genes to human cells. When it comes to cell division, most of the DNA in each chromosome is irrelevant. But to be copied properly and sorted into the two daughter cells, a chromosome must have two types of highly specialised DNA sequences-one somewhere in the middle called a centromere, and bits on either tip called telomeres. Last year, Huntington Willard, a molecular biologist at the Case Western Reserve Medical School in Cleveland, Ohio, and his colleagues reported that they had created artificial chromosomes in cultured human cells that replicated every time the cells divided. "We cultured them for six months, and they looked like perfectly normal chromosomes," say Willard.

Because these human artificial chromosomes (HACS) promise the ultimate in genetic engineering, they have done more to fire up discussion about human germline engineering than just about any other technology. Once perfected, HACs will make it possible for genetic engineers to ship complex custom-made genetic programmes into human embryo cells. Each gene could come with control switches geared to trip only in particular tissues, or when the patient takes a particular drug. Suppose, for instance, that men in your family tend to get prostate cancer at a young age. Insert into your fertilised egg an HAC containing a gene for a toxin that kills any cell that makes it, and two switches for that gene one that is turned on only by prostate cells and another by ecdysone, an insect hormone that humans cannot make. Nine months later, you're delivered of a bouncing baby boy. Fifty years later, he gets prostate cancer. He takes ecdysone, which activates the prostate poison, killing every prostate cell in his body Even cancer cells that have spread to other parts of the body should be wiped out. It's scenarios like this-dreamt up by John Campbell, a molecular biologist at the University of California, Los Angeles, who helped to organise the March symposium-that make the promise of human germ-line engineering so tantalising. Hood is convinced that the benefits of germ-line engineering are going to be substantial: "We could probably engineer people to be totally resistant to AIDS, or to certain kinds of cancers. We might engineer people to live much longer. I would say all these are good qualities." Willard agrees that the prostate cell scheme, or others like it, might someday be made to work. At the moment, his team is trying to create HACs that contain specific human genes so that they can check that the genes function normally in cell cultures. "Everybody wants to [use artificial chromosomes] in mice," he says, "But we're years away from even contemplating putting HACs into humans." Still, when that day comes, as most experts predict it will, who and what will be the first candidates for human genetic engineering? Geneticists are more willing to kick around the possibilities than ever before. Gruenert speaks for many when he says that the crucial issue is whether germline engineering would save lives and prevent suffering. "For medical reasons, I have no problems," says Gruenert. "But for making superwomen or supermen? I have some problems with that." The first candidates for human genetic engineering are likely to be children who could inherit a disorder that kills young, is incurable both now and for the foreseeable future, and is caused by a relatively simple defect. Tay-Sachs disease, which causes the brain to degenerate in the first few years of life, is just such a disease. Fix the gene, goes the argument, and you stop the disease both in that child and all his or her offspring. If the safety issues are resolved, the idea of wiping out such diseases could sway the opinions of the public and regulatory agencies, paving the way for the first attempt at human germ-line engineering, says Jeremy Rifkin of the Foundation on Economic Trends in Washington DC, a longstanding opponent of biotechnology. "I've seen this pattern before in biotechFirst there is some discussion in journals, then a conference, then they go ahead and do it. I think there are protocols being readied now, and we'll see them within a year or two."

Strange bedfellows

Rifkin may have some unusual allies in his fight against human engineering. Many researchers who are otherwise decidedly pro-biotechnology are vocal in their concerns about engineering humans. Allen Roses, who heads Glaxo Wellcome's worldwide genetics research effort, is emphatic that any attempts at germ-line engineering would be "morally questionable". The milder-mannered Francis Collins, director of the National Human Genome Research Institute near Washington DC, says simply: "It is very hard to come up with compelling scenarios of why you'd want to." Collins, Roses and others take issue even with the idea of using genetic engineering to prevent genetic disorders. They point out that parents known to be at risk of certain serious genetic abnormalities are already offered genetic testing and the option of an abortion if their fetuses have the disorders. Using this approach, the number of Tay-Sachs births has been reduced by more than 95 per cent among American Jews. For women willing to have IVF, an embryo can even be tested before pregnancy starts. Of course, repairing rare genetic defects is not the only factor likely to endear genetic engineering to the public. Who could resist the chance to bequeath their

children freedom from Alzheimer's, cancer, heart disease and diabetes? Then there's the possibility of cosmetic changes and enhancements that have nothing to do with saving lives and preventing disease. Many behaviourat traits, from cheerfulness to sexual orientation, have already been linked, if tenuously, to variations in single genes. Many more such links will be reported in the near future. "There will come a time when we will understand enough to manipulate even complex genetic systems," says Hood. "For example, we will be able to dramatically affect intelligence. That, I think, will be pretty irresistible." "Evolution is being superseded by technology, and the time scale will be far more rapid," says Stock. "Humans are becoming the objects of conscious design." And no matter how wild the idea of designer children sounds now, technology has a way of making believers out of sceptics. Silver argues that parents will provide the market forces that will eventually make germ-line engineering of humans routine. When IVF was first being developed in the 1970s, he points out, doctors and lay people alike thought the idea absurd and repellent. Even though success rates are still low, IVF created such demand among couples with fertility problems that it has become widely accepted and commonplace. For now, however, the regulative barriers are firmly down, even as the research hurtles forward with breathtaking speed. Which is perhaps why talk about engineering humans is now coming into the open. It no longer makes sense to shy away from discussing what we're going to do when all the technical obstacles are overcome, and genetic engineering offers us the profound power to sculpt our children-and the future of our species.

Robert Taylor is a science writer in Washington DC

Further reading. "Human artificial chromosomes coming into focus", by H. F Willard, Nature Biotechnology, vol 16, p 415 (1998) "Variations on a theme: cataloging human DNA sequence variation", by F. Collins, M. Guyer, and A. Chakravarti, Science, vol 278, p 1580 (1997) "Human factor lx transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts', by A. E. Schnieke and others, Science, vol 278, p 2130 (1997) "Rhesus monkeys produced by nuclear transfer", by L. Meng and others, Biology of Reproduction, vol 57, p 454 (1997) "Cloning for profit", by G. B. Anderson and G. E. Seidel, Science, vol 280, p 1400 (1998)

For more on the symposium 'Engineering the Human Germline", see http://www.ess.ucia.edu/buge.

Ethical Dilemmas NS 17 Oct 98 Inside Science

Susan Aldridge

ETHICS is the study of the moral value of human conduct and of the rules and principles that govern it. Often known as moral philosophy, it seeks to distinguish between the good, what is bad, and ways of implementing these rules. The thomy question of how to define "good" and "bad" lies at the heart of ethical decision making. The Greek philosopher Plato said that the most important - and one of the most difficult - question to answer in real life is "What is the good?" It is hard to define exactly what we mean by ethics, even experts disagree. Put simply, it refers to standards of behaviour governed by what is agreed to be acceptable or correct. Basic categories of ethical concem fall into two classes: intrinsic and extrinsic. Intrinsic concerns deal with things that are thought to be wrong in themselves, such as nuclear weapons and human cloning. Extrinsic concerns involve the application of developments, neutral in themselves, but open to misuse or the cause of harm to others, This classification includes a new drug or an over-powered car. Many ethical arguments hinge upon the weighing of risks against benefits. Risk benefit analysis is the basis of an ethical system called utilitarianism, whose exponents included philosophers Jeremy Bentham (1748-1832) and John Stuart Mill (1806 - 1873). In a nutshell, utilitarianism argues that things are right or wrong in proportion to the amount of pleasure or pain they produce for communities or individuals. Another school of ethical thought is based upon natural law. Here, ethical decisions are made on the basis of how unnatural a scientific development is. Under Natural Law, genetic engineering is seen as intrinsically wrong, as is IVF. But the idea that natural is good and unnatural is bad has weaknesses. Natural disasters, such as earthquakes and volcanoes, cause immense damage and suffering, and many plants contain potent toxins. You can also argue that all scientific developments are, to an extent, unnatural. Natural law also encourages respect for the natural world. And it touches on the concept of human dignity: people should not be used as a means to an end, but ascribed value in their ovm right. This would forbid, say, the generation of embryos or fetuses to be us ants surgery. it is not just biology and medicine that give rise to ethical problems, of course. Take, for example, the 16ng debate over nuclear power. Supporters say it is a clean source of energy which can save the planet from global warming and provide developing countries with the energy they need to get ahead. Critics point out the risk of a major nuclear incident has been underplayed by the industry.

ALL progress in science and technology has an impact on people's lives. Often these effects are positive-antibiotics, computers and electricity have made our lives safer, easier and more comfortable. But inventions can bring suffering and injustice, such as nuclear war, pollution and road accidents. How do we decide what is the right and wrong use of science? These difficult choices lie in the realm of ethics. Few of us would argue over the chemical formula of sulphuric acid, or the right names for the bones in the human skeleton, but when it comes to ethical questions there is often disagreement on what is "right". Views on issues such as genetic screening and clinical trials are affected by religion and culture. And what is acceptable, changes over time. in 1967, many condemned the first heart transplant as unnatural. But most people now accept these operations as life savers. In 30 years time, will we happily accept the transplantation of animal organs to humans? Weighing benefits against risks can often provoke strong feelings, as with the arguments over animal experimentation. Animals are used in three main ways these days: in medicine, cosmetics and transgenics. Each raises different questions about risk versus benefits. Thousands of lives are saved every year through medicines and surgical techniques that were first tested out on animals. Research into cancer, mental illness and neurological disease such as multiple sclerosis-all conditions for which there is a clear need for new treatments-rely heavily on animal experiments. In this case, most of us agree that the benefits in terms of reduced human suffering outweigh the inevitable suffering inflicted on the animals. In 1990, for example, 3.2 million animals experiments took place. But a minority of animal experiments are carried out to test cosmetics and toiletries. Here the balance seems to tilt in the other direction. Some of these items are undoubtedly necessary, but should animals suffer just to bring a new kind of makeup or deodorant to supermarket shelves? Companies could instead be asked to use ingredients already known to be safe. 'ftansgenic animals, which carry genes from humans and other species, can be used to test new treatments for diseases such as sickle-cell anaemia. New drugs can be developed by creating transgenic sheep and cattle that carry genes for human proteins that are produced in their milk. Dolly, the cloned sheep, was created as part of this research programme (although she is not herself transgenic). In this case, the science is so new that judging long-term benefits and risks is difficult. Some say that animals have rights and should never be subjected to experiments, regardless of the benefits to humans. They argue that even though chimpanzees, farm animals and laboratory mice are not members of our species, this does not give us the right to treat them as we please. Animal rights activists believe humans are guilty of "speciesism", a notion suggested in 1975 by the Australian philosopher Peter Singer. Even if we argue that humans have greater rights, because they are rational and self-conscious, we have to realise that chimpanzees show intelligence, some selfawareness and possess a sophisticated social awareness.

Experiment or not The three "Rs"

ALERT to these ethical problems the British government brought in the Animals Act in 1986 to control animal experimentation. This incorporates the "Three Rs" principle developed in 1959 by two researchers funded by the Universities Federation for Animal Welfare. Rex Burch and William Russell had travelled Britain interviewing scientists about good practice in the treatment of experimental animals. The three Rs stand for reduction, refinement and replacement. Reduction refers to cutting the number of animal experiments, for example, by harmonising regulations between different countries so that experiments do not have to be repeated in each country. Refinement means extracting the maximum information from the minimum number of experiments. And there are many possible replacements for animal experiments, including the use of so-called "lower" organisms-the horse shoe crab, for example, tissue slices, cell cultures and computer models (see Figure 2). In theory, a research scientist cannot use an animal in research if the information could be obtained by one of these other methods. In practice, few of the replacements are yet widely accepted as valid alternatives to animal experiments. instead of animals, we could use people in medical trials. Human clinical trials, c@irried otit before l new drug or surgical treatment is niade generally available, differ from animal tests in two ways. Firstly, volunteers have to give their fully informed consent. Animals cannot consent, for obvious reasons. And those recruited on clinical trials do not usually include children or women of childbearing age (because a fetus could be exposed to the drug) and prisoners. Secondly, there should never be any intention to cause harm to the volunteer. This is not true with animals where most are killed at the end of the experiment, although there is a legal requirement for pain to be kept to the minimum.

There is a serious ethical issue in human trials, however. To get reliable information on a new treatment, it is necessary to assign the volunteers either to a treatment group or a control group that receives only a "dummy" treatment, or placebo (see inside Science No. 65, "How a drug is born"). Patients who are seriously ill, however, are understandably anxious to receive the best treatment. Some doctors feel that depriving half the patients of treatment is unacceptable; and it is sometimes difficult to recruit patients to trials, even when the treatment and control groups are swapped halfway through. Biotechnology and genetic engineering (see Inside Science No. 105 "Growth industry") raise many new ethical issues. Genes are, of course, the basic material of these technologies, and commercially useful genes can be found all over the world-in human populations, tropical plants and even at the bottom of the ocean But who owns these genes and who is going to benefit most from their exploitation? The UN Convention on Biodiversity was agreed at the Rio "Earth Summit" in 1992 seeks to address these concerns. It plans to introduce and enforce ethical rules. Instead of biological resources such as plants, cells and genes being regarded as the common property of humanity, they now belong to their country of origin. Before this, a drugs company from anywhere in the world could bring plant and soil samples back from any other country without any questions being asked. The company could screen its samples for new antibiotics or painkillers, for example. If it found anything worth exploiting, the rights in that discovery belonged solely to the company. Now companies must enter into formal agreements with governments before collecting any samples. Some of the profits from a successful drug must now be ploughed back into the country which gave rise to the original source material. The ethical issue becomes even more sensitive when it comes to dealing with human genes. The Human Genome Diversity Project is sampling DNA from populations around the world. Part of the wider Human Genome Project which was set up in 1990 to identify the 60 000 to 80 000 genes carried by humans, it will study differences between the genetic make-up of ethnic populations, which, when analysed alongside data for the prevalence of disease, may point to genetic causes and possible treatments. However, Native American groups in the US object to their genes being studied for fear that the information will be used to exploit or discriminate against them.

Improving nature: Plant genetics

PLANTS which have been genetically modified are already being grown in open fields, and modified bacteria and viruses are often used to carry genes into plants and animals. Developers want to boost crop yields for the world's expanding population by protecting the plants from pests, or to help the environment by enabling a more efficient use of weedkillers. But critics point out that making crops resistant to herbicides so that only weeds get killed when herbicides are sprayed might encourage farmers to be careless. If the herbicide does not harm their crop, they may stop worrying about how much they use and perhaps be less careful about where they apply it. There is another danger too: genetically modified plants might breed with wild species and so spread their genes far and wide. Supposing, for example, a gene for herbicide resistance were to find its way into a weed. The creation of a superweed that dominated the ecosystem would be an alarming development and many people would like to wait until we know more about the risks before proceeding further with plant genetic engineering.

Futuristic babies Beyond the test tube

AND it's not only plant reproduction that perturbs us. There are now 13 ways to have a baby other than by sexual intercourse. In vitro fertilisation (IVF) is a well-established technique, producing so-called testtube babies. The technique now includes the use of donor sperm and eggs, and embryo freezing. in future, women may even be able to have babies by cloning their own body cells. Assisted reproduction has the obvious benefit of bringing the pleasure and joy of parenthood to childless women, whether they are infertile single women, lesbians, postmenopausal women or women wanting a dead partner's child. For some, these new candidates for parenthood pose ethical problems. For example, one "cost" of fVF is that children put up for adoption lose out if an infertile couple opts instead for IVF, while the child of a postmenopausal mother runs the risk of losing her care and support before reaching adulthood. And all these techniques are expensive, so how can we be sure that people with other medical conditions are not being deprived of scarce resources as a result? Fertility drugs are an essential part of IVF, but they make the rate of multiple pregnancy increase from between I and 2 per cent to 25 per cent. it may sound ideal to provide an infertile couple with a readymade family in the form of twins, but there are many risks associated with multiple pregnancy. The mother is more likely to suffer complications such as high blood pressure, while the babies may be born prematurely, possibly suffering lifelong health problems as a result. One way around this problem is a technique called selective reduction: where one or more of the fetuses is aborted to give the remaining ones a better chance. For everyone involved, this is a difficult decision to make.

The ethical dilemma here depends upon the status given to a sacrificed fetus: whether or not it has equal rights with the baby (or babies) that survives. These ethical issues resemble those faced by other innovative medical procedures. But IVF and related technologies have created new questions. Firstly, interference with the processes of reproduction and birth is seen by many people as being unnatural; some accuse the doctors of "playing God". Then there are ethical issues about the parental rights and responsibilities of all those involved in these new reproductive processes (see Figure 3). When we separate biological and social parenting, it has a radical impact on our ideas of what makes a family. IVF may also lead to the creation of "spare" embryos, which are not implanted into the uterus. How should we treat these? Parents can opt to have these frozen for further use, donate them to research or let them perish, but there was an outcry recently when a woman proposed to store an embryo until it suited her to carry it to term. It is also possible to create embryos in the test tube specifically for research purposes. As with selective reduction, attitudes towards embryo research depend upon the status accorded to the embryo. In Britain, an embryo is seen in the eyes of the law as rather less than a living child or adult, but still worthy of respectful treat ment. Embryo research, which is permitted up to 14 days after fertilisation, is strictly con trolled by the Human Fertilisa tion and Embryology Authority. of course, there has been a good deal of debate about the ethics of attempting human cloning. We have to distinguish between cloning of cells for possible medical uses on a patient and an entire cloned baby. Cloned tissue could be used for transplants, in which case human cloning would have some potential benefit-and would cut down on animal experiments. But most people see the cloning of a new human as unacceptable, mainly on the grounds that it is an offence against human dignity and that each individual has a right to his or her own genetic identity. in fact, there is already a market for clones, but not human ones. People are already attempting to have their pets cloned. But do animals have a right to their genetic identity? Should cutting edge research like this be used to satisfy the need for a pet? On the other hand, might cloned pets make people liappy-as well as contributing to research?

Testing zone Hard choices

GENETIC advances have helped the treatment of inherited diseases. Single gene disorders affect about I per cent of the population, while many more common diseases, such as asthma, diabetes, and cancer, have a genetic component. It is now possible to test high-risk families, or populations, for the presence of many different defective genes (Figure 5). As the Human Genome Project nears completion, many more genes involved in disease will be discovered. Gene tests, therefore, are certain to become more widespread in the future. There is also the prospect of using gene therapy to insert healthy genes into ordinary body cells (somatic cells), or even eggs and sperm (germline cells). There are clear advantages to gene-based medicine. Pre-natal diagnosis of a severe disorder like sickle-cell anaemia allows the family the option of abortion. This saves the whole family the burden of coping with an affected child. it also saves the suffering of the child who would otherwise have been born. Tests given to adults to assess their susceptibility to cancer enables them to have more frequent medical checks. And when tests on a member of an at-risk family prove negative, it does enable them to make plans for the future with confidence. Genetic testing also brings risks and costs. First, pre-natal testing followed by termination deprives a child of the chance of life, of some value, however great the suffering involved. There is also the question of how serious a dis ease should be before pre-natal testing is an ethical option. Would people not want to have children with diabetes, say, if the relevant genes were discov ered, even though people with diabetes can lead a normal life with treatment? And maybe parents will soon have the option of choosing embryos without genes which may be found to influence baldness, low intelligence or even homosexuality? In 1997 a Gallup poll of British parents revealed that many would opt for genetic enhancement of their children if they could. If it were proved that genes for aggressive behaviour and homosexuality existed: 18 per cent would choose an abortion against aggressive behaviour and 10 per cent against homosexuality, while 5 per cent would like a physically attractive child. Developments such as these could lead to the development of a genetic underclass in society, repeating the eugenic horrors of Nazi Germany. Fantastic as these ideas may seem, we may see discrimination on genetic grounds in the near future. Insurance companies could refuse policies to people carrying faulty genes. There is also concern that employers could use genetic tests to ensure a super-healthy work force, thereby neglecting their responsibility to provide a decent working environment. Genetic tests can also cause psychological suffering in an at-risk family, particularly where incurable diseases, such as familial Creuzfeldt-Jakob disease (CJD) or Huntington's disease, are involved. Because these diseases develop in middle age, the person testing positive may have no symptoms at the time, but is suddenly facing a death sentence. They may already have had children, who may be carrying the gene. There is also the issue of whether to share the information with other family members. This is why genetic testing is only done in specialist centres, where full information and counselling are available. With so many ethical issues raised by modern science, it is easy to understand why there are now several university departments and legislators who specialise in ethics. Their work will play an increasing role in helping us to play our part in deciding between right and wrong in scientific progress.

FURTHER READING Clones, Genes and Immortality; Ethics and the Genetic Revolution by John Harris (Oxford University Press, 1998); Attack of the Genetically Engineered Tomatoes: The Ethical Dilemma of the '90s by Nicola Hamilton (Whittet Books, 1998); Improving Nature? The Science and Ethics of Genetic Engineer' by Michael J. Reiss and Roger 'ng

Straughan (Cambridge University Press, 1996). New Scientist's special issue on genetic engineering will be published on 31 October 1998.



Designer babies - ethics

Science is on the brink of handing us the key to our own creation, of giving us the power to redesign ourselves.

There is enormous potential for good. Diseases could be eradicated, death forestalled, human potential extended. But behind that promise lurks a long, cold shadow of doubt.

What becomes of parenthood, of individuality, of the notion of fate in a world in which human beings are not just born but engineered? What will life be like in a world in which we have the power, as developmental biologist Stuart Newman puts it, to turn "human beings into manufactured objects"?

The new science that is raising these questions is called "germline engineering." What it means is designing our babies to our own specifications. We would choose the genes that determine human potential -- height, hair color, intelligence, longevity, even many personality traits -- instead of leaving it up to the messy, unpredictable process of natural procreation.

Experts disagree on when this will be possible. Perhaps in 10 years. Perhaps not for many decades. But they do agree it is coming.

"We live in a huge supermarket," says Leslie Fiedler, an essayist and cultural critic at the University of Buffalo. "And one of the things that's going to be offered for sale in the future is making yourself a better human being. Living longer, growing taller, jumping higher." Some applications, such as eradicating fatal defects including cystic fibrosis and Tay-Sachs disease, unquestionably would be a boon to humankind. But would a germline intervention that prevented obesity be the greatest public health advance of the 21st century or the pathological vice of a vain society obsessed with thinness? People endowed with the power to shape their genetic legacy would have to decide what is normal. Are people who are mentally retarded, blind or manic depressive defective or mere variations from the norm?

Where is the line of acceptability between preventing severe birth defects, on the one hand, and genetically engineering a homogeneous race of "perfect" humans, on the other?

"The knee-jerk reaction is that I don't want a child that has something wrong with it," says Anne Boyle Cross, a Ph.D. candidate at Yale University who is expecting her first child later this year. "But there are worse things than having a blind child or a mentally retarded child."

Some parents would almost certainly demand enhancements to give their offspring advantages they themselves never had. Ambitious parents might want to give their children genes for memory and intelligence.

Music lovers might want children with perfect pitch. Frustrated high school heroes might want genes that would improve their kids' chances of becoming world-class athletes.

"The question is, 'So what?'" says Erik Parens, a fellow at the Hastings Center for Bioethics in Garrison, N.Y. "Don't parents seek all the advantages they can for their children? Piano lessons,
ballet lessons, and the like?"

But what do you do with a kid who is genetically engineered to play football but would rather play violin? With natural procreation, no one is to blame for our genetic makeups. They are simply the luck of the draw. But in a world where parents select their childrens' genes, they would bear responsibility for every choice.

What if your parents decided against a particular genetic improvement and you felt you should have had it? Conversely, what if your parents chose a trait for you that you wish you didn't have?

Would you be resentful? Could you sue?

This sort of thing could create incomparable anguish, especially since recent research suggests that some of the same genes that confer desirable characteristics also contribute to undesirable ones. For example, the same genes that contribute to manic depressive illness also seem to confer artistic creativity.

Disable the mental illness genes, the argument goes, and you could deprive the world of future van Goghs, Hemingways and Poes. Yet "Starry Night," "The Sun also Rises" and "The Telltale Heart" were paid for with turbulent lives and violent, early deaths. Vincent van Gogh and Ernest Hemingway both committed suicide. Edgar Allan Poe drank himself to death in a Baltimore tavern.

Furthermore, genetic tinkering that would unquestionably be good for the individual could be a mixed blessing for society. Why not bless our babies with the genes that contribute to the remarkably long lives of a small percentage of the population? But what if everyone lived to be 100? Or 120? The world would become an increasingly crowded place. How would we find room for the next generation?

Another complication: Germline engineering will not be free; not everyone will be able to afford it. Will this create a new, genetic gap between rich and poor? Will it lead to a world in which babies of the rich will be guaranteed genes for intelligence, longevity and other desirable traits while the babies of the poor will have to take their chances?

And what of the nature of parenthood itself? Today, babies born to us are truly ours. Half of their inherited traits come from the father and half from the mother. Genetically designed babies would have genes that would come from neither side of the family. They would be the product not of blessed union but of a biotechnological revolution.

Will parents and children sense that genetic disconnection?

"I want half of those genes to be mine," says Cross, the expectant mother. "I don't want even one percent to be an outside party's."

On the verge of his 83rd birthday, essayist Fiedler has witnessed an era of great strides in medicine: the extension of life expectancy by decades, the conquest of infectious disease, the eradication of smallpox. But to what end?

"Certain diseases have disappeared from the world. And people do live longer and run faster and jump higher. But they don't seem to be any happier," Fiedler says. "I grew up thinking when I got old enough I would be finding some answers. And all I find is more questions."

No one knows where germline engineering will lead, but history makes one thing clear. From the harnessing of fire to the splitting of the atom, mankind has never made a scientific discovery and then failed to use it.

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