THE HANDSTAND

Human Cloning and Genetic Modification-
The Basic Science You Need to Know

I. GENES
Genes are strings of chemicals that help create the proteins that make up your body. Genes are found in long coiled chains called chromosomes. They are located in the nuclei of the cells in your body:

II. "THREE WAYS TO MAKE AN EMBRYO"
In sexual reproduction a child gets half its genes from its mother (in her egg) and half from its father (in his sperm):

Cloning is an asexual form of reproduction. All the child's genes would come from a body cell of a single individual:

Who is the clonal child's genetic mother or father? As we understand those terms, a clonal child wouldn't have a genetic mother or father, it would have a single 'nuclear donor.' If a man cloned himself, would the child be that man's son or his twin brother? It would be neither, it would be a new category of biological relationship: his clone.

III. STEM CELLS
Stem cells are primordial cells capable of developing into a variety of types of cells. Some stem cells are found in the adult body. Others are found in very early embryos. These stem cells can be cultured in petri dishes and potentially used to generate "therapeutic tissues" or "spare organs":

Many people support the use of stem cells of both types for such therapeutic purposes. Many others support the use of adult stem cells for this purpose but oppose the use of embryonic stem cells, because they oppose the destruction or manipulation of human embryos.

IV. HUMAN CLONING: A CRITICAL DISTINCTION BETWEEN TWO APPLICATIONS
1. Reproductive cloning uses the cloning procedure to produce a clonal embryo which is implanted in a woman's womb with intent to create a fully formed living child--a clone-as shown in diagram 3 above..

2. Therapeutic cloning uses the cloning procedure to produce a clonal embryo, but instead of being implanted in a womb and brought to term it is used to generate stem cells, as shown in diagram 4 above.

The purpose of using clonal embryos to generate stem cells is to allow creation of tissues or organs that the clonal donor can use without having these tissues or organs rejected by their body's immune system.

Most people oppose reproductive cloning. Some people oppose reproductive cloning but support therapeutic cloning. Others oppose therapeutic cloning as well as reproductive cloning, either because they are opposed to the destruction of embryos as a matter of principle, or because they feel the acceptance of therapeutic cloning will set us on a slippery slope to the acceptance of reproductive cloning and human genetic manipulation.

It is possible to support stem cell research and still oppose research involving therapeutic cloning.

V. HUMAN GENETIC ENGINEERING
Human genetic engineering means changing the genes in a living human cell. Suppose you had a lung disease caused by defective genes in your lung cells. If there was a way to fix those genes, you might be cured.

Scientists change the genes in living cells by putting the desired "new" gene into a little virus-like organism which is allowed to get into your cells and which inserts the new gene into the cell along with the "old" genes:

VI. HUMAN GENETIC ENGINEERING: A CRITICAL DISTINCTION BETWEEN TWO APPLICATIONS
1. "Somatic" genetic engineering is genetic engineering that targets the genes in specific organs and tissues of the body of a single existing person without affecting genes in their eggs or sperm. Somatic gene transfer experiments are currently undergoing clinical trials, with mixed results to date. But they may someday be effective. Diagram 5 above shows how somatic genetic engineering works.

2. "Germline" genetic engineering is genetic engineering that targets the genes in eggs, sperm, or very early embryos. The alterations affect every cell in the body of the resulting individual, and are passed on to all future generations. Germline engineering is banned in many countries but not in the U.S. Diagram 5 shows how germline genetic engineering works.

[note: The term "somatic" comes from the Greek "soma" for "body." The term "germline" refers to the "germ" or "germinal" cells, the eggs and sperm.

VIII. PRE-IMPLANTATION GENETIC DIAGNOSIS AND SELECTION (PDS)
Many people assume that germline engineering is necessary to allow couples at risk of passing on a genetic disease to avoid doing so. This is not so. Procedures already exist that make this possible, including adoption and gamete and embryo donation. In addition the alternative of pre-implantation diagnosis and selection allows couples to have a child that is fully genetically related to both of them and which does not carry the genetic disease about which they are concerned.

The PDS procedure begins in the same way that germline engineering would, with an IVF procedure, but instead of seeking to change the genes in unhealthy embryos it simply selects the healthy embryos themselves for implantation in the mother:

This technique is more straightforward than germline genetic manipulation, and does not open the door to an out-of-control techno-eugenic human future. The only situation in which germline engineering would be required over pre-implantation selection is one in which a couple would like to endow their child with genes that neither member of the couple possesses. This is the "enhancement" scenario, which we believe would lead to a dystopic human future if it were allowed. PDS, on the other hand, would have only a minimal effect on the human genome, even if it were widely used, because the procedure selects from the range of existing human traits. But engineering the genes by means of germline modification would allow novel forms of human life to be created within one generation.

While pre-implantation diagnosis and selection can be used for the acceptable reasons of preventing genetic disease, it could also be used in ways that societies might find unacceptable, eg., to select for cosmetic, behavioral, or other non-disease traits. Societies have the right and responsibility to decide which uses of such screening technologies should be allowed and which should be banned.

Click here for a printable PDF version of this brochure

ARHP's Genetic Engineering Resource Center

Read a Transcript from ARHP's Recent Debate on Genetic Engineering

Many sections of this ARHP educational tool are taken from Human Cloning and Genetic Modification: The Basic Science You Need to Know' by the Center for Genetics and Society, with their permission.

Center for Genetics and Society
436 14th Street, Suite 1302, Oakland, CA 94612
tel: 510-625-0819
fax: 510-625-0874
e-mail: info@genetics-and-society.org
Website: www.genetics-and-society.org

MEDIA DISCUSSION ON CLONING

A clone is simply a group of individuals containing exactly the same genetic material.

Traditional viewpoint

Originally the term clone was used to cover plant material simply derived from asexual reproduction or vegetative reproduction - tubers, plantlets, offsets etc. and cuttings, grafts etc.

However, the term may also apply to animals which naturally reproduce asexually,

e.g. Amoeba reproduces solely by asexual reproduction to produce genetically identical offspring, and some animals alternate between sexual and asexual stages which result in clones being formed.

Viewed in this way, identical (non-fraternal) twins are fairly commonplace examples of a natural cloning process.

More modern developments

The principles of cloning have been applied to some more fundamental experimentation in plants and animals.

Horticultural applications

It has been discovered that plant cells which have apparently finished differentiation can be encouraged to revert to an unspecialised state called a callus, which can be caused to grow on special liquid/gel media. This has been done with many types of plants - from normal horticultural species such as carrots and cauliflowers to more exotic species such as new varieties of flowers and palm oil plants. Since the growth involves nuclear division by mitosis and cell division, the resulting cells are identical.

The mass of undifferentiated tissue can be divided into individual cells without damage, and then left to grow into more masses of tissue, similar to an embryo inside a seed. On transfer to different media, these embryos can be persuaded to develop into miniature plants inside special illuminated incubators in the laboratory. This process is called micropropagation.

These plants may then be transferred and grown on using standard horticultural techniques - pots in glasshouses, etc., before release.

Possible medical application

Cloning simpler organisms

It is known that in simpler organisms the differentiation process is less inflexible, and that damage to the body can be overcome due to cells re-growing lost tissue. Much experimental work along these lines has been carried out in in amphibians.

Experiments on amphibian eggs (frog spawn) have proved that it is relatively easy to transfer a new nucleus (from a body cell) into an egg cell which will then usually develop normally according to the genetic information in the transplanted nucleus. This technique has the potential for producing large numbers of genetically genetically identical individual organisms.

Cloning mammals

It had been thought that in mammals (including Man), the situation was somewhat different and that it was very difficult to persuade nuclei from differentiated cells to divide again, when inserted into other cells.

However, with the advent of techniques including nutritional and temperature conditioning of cells taken from the body of higher animals, it has proved possible to clone mammals, e.g. Dolly the sheep.

Several practical problems remain to be solved; the reliability of the process could be increased, and it has transpired that cloned offspring effectively age prematurely - due to progressive deterioration of structures called telomeres at the edges of chromosomes. However some believe that there are a variety of advantages in being able to clone agricultural animals by splitting early embryos.

Although some of the practical difficulties of cloning whole mammals have been overcome, there is little likelihood of applying this cloning technique to humans.

Cloning and embryo cells

In embryos, cells derived from a fertilised egg divide repeatedly to produce tissues for the developing foetus. In an embryo, some dividing cells are becoming differentiated according to their function, but there are also unspecialised stem cells which may be persuaded to divide into different types of cells, depending on the body's requirements.

In the laboratory, cells have been taken from human embryos (normally obtained via an abortion) or from foetal blood cells in umbilical cord. A more hopeful source is the use of "spare" early embryos fertilised in a dish by IVF (in vitro fertilisation) techniques.

There has been much controversy over these procedures, partly based on the origin of the biological material in the first place and partly due to misgivings over the implications of continuing cell division.

However, restrictions have been applied as to the use of these techniques in studying the development of these cells. The human embryology authority had limited research to early stages after fertilisation only. Cell biologists hoped that if allowed greater freedom then research into many genetic diseases, e.g. cystic fibrosis, could benefit.

The latest development in this field is that British MPs have voted to allow research into stem cells.

It is especially likely to be of use to researchers studying degenerative diseases, e.g. Alzheimer's, but also in the study and treatment of a variety of cancers.

There is no possibility that these cells will develop into a new individual unless implanted into a uterus. Human cloning "for reproductive purposes" remains illegal.

What slippery slope?
We have nothing to fear from the cloning of human embryos by South Korean scientists, says Christopher Reeve

Friday February 13, 2004
The Guardian

This is a historic breakthrough that could revolutionise medicine. A woman with multiple sclerosis, for example, could use one of her own eggs and have a piece of her skin used to extract DNA, which could then be put into that unfertilised egg - and cells could be derived that might cure her of MS. At this point, we cannot know how long it will take to deliver this breakthrough to people with diseases and disabilities. I wouldn't want to speculate with a number, because you're bound to be wrong. If you say two years, if you say 10 years - both are likely to be wrong.

Oversight will be absolutely crucial - there is the potential for abuse, and the technology of cloning should never be used to reproduce human beings. But those who say that therapeutic cloning will inevitably lead to reproductive cloning are mistaken. We often hear about the slippery slope. But here in the US, when we lowered the voting age from 21 to 18, it didn't slide down to 12. It stopped at 18. There are very strict laws about selling liquor that go back to Puritan times. There are all kinds of regulations covering what doctors can and cannot do. Everywhere in society we see regulation working effectively. The fact is that somatic cell transfer has now been achieved, and I think that is something to celebrate.

What is crucial is that here there is no fertilisation. And while it takes 14 days for even a fertilised egg to be recognisable as human, scientists are talking here about taking stem cells at the three- to five-day stage. I do not believe that represents the destruction of a human embryo. And because these stem cells contain the patient's own DNA, we don't face the problem of rejection by the patient's immune system, or the possible formation of tumours and runaway overdevelopment: this breakthrough, as I understand it, solves those problems.

I hope South Korea will share its methodology with other countries that have a progressive policy on stem cell research. Scientists around the world are making very important advances using all kinds of technology - many of which have nothing to do with stem cells. There are all kinds of approaches going on, and that's what I'm most encouraged by, not one particular technology. I am an advocate for progressive scientific research, for relieving the suffering of millions of people around the world who live with incurable diseases. Stem cells are only part of the equation - whether they come from the bone marrow or the umbilical cord or the brain; or whether they are taken from excess fertilised embryos that are going to be discarded as medical waste from in vitro clinics - they are very important, but they are only part of the equation.

Politically, though, the issue is at a stalemate at a federal level in the US. There are two competing bills in the Senate - one that would allow somatic cell transfer and one that would ban it - and neither has enough votes. At a state level, however, there have been successful initiatives in California and New Jersey. And I am hopeful that a number of states will pass their own legislation allowing research in the very near future, before the presidential elections.

Meanwhile, I am grateful that countries around the world, led by the UK, Israel, Sweden, South Korea, Singapore, and a number of others, are going forward with research. Because they do, there will always be the option for patients to travel to those countries, or for the technology to be imported eventually. The most important thing is that, somewhere in the world, the work is being done.

· Christopher Reeve was talking to Oliver Burkeman. Forwarded by John Massey
++++++++++++++++++++++++++++++++++++++++++++++++++++++

Unlocking the secrets of the nucleus

Richard Gardner
Friday February 13, 2004
The Guardian

The results published by the team from South Korea and the United States represent a promising step forward.

Most research on embryonic stem cells at the moment is being done using spare embryos from in vitro fertilisation. If these stem cells were eventually used to treat patients, they would run the same risks of rejection that are such a big factor in organ and tissue transplants today.

The problem is that the stem cells would not be genetically compatible with those of the patient.

This is where cloning technology might hold a solution. If a cloned embryo was produced using the nucleus of a cell from a patient, the genetic makeup of the stem cells extracted from it would be almost identical to that of the cells in the patient's body.

Although some people have suggested that this might one day become a routine therapy, the process of cloning and cultivating stem cells to produce replacement tissues and organs would remain extremely difficult and time-consuming.

But therapeutic cloning may lead to even more useful advances. Ultimately, researchers would like to learn the secret of reprogramming the nucleus, since it is this that controls the cell.

We know that the process of cloning, in which a nucleus is transferred from an adult cell into an egg cell and an electrical current or chemical stimulation is applied, produces this reprogramming. The adult nucleus is reset and becomes the nucleus of a single-celled embryo.

If therapeutic cloning allows the secret of this reprogramming process to be unlocked, then potentially a whole range of medical leaps forward could be explored.

Could cells adjacent to the damaged part of an organ be reprogrammed to produce replacement cells, such as in spinal injuries? Could defective cells be reprogrammed to act normally, to tackle cancer for instance? The possibilities would be truly amazing.

More work, including further investigation of yesterday's results, is now needed. They may only have stimulated a process called parthenogenesis, in which an egg cell starts to undergo development, but without the involvement of the adult nucleus. In this case it would not be the adult nucleus in control, and the embryo would not be a true clone.

But we remain hopeful that they have truly taken the first steps towards successful therapeutic cloning. It is important that legislation and funding allows such research to continue, so that we might realise these possible great benefits to human health.

· Professor Richard Gardner is chairman of the Royal Society working group on stem cells and cloning
*****************************
Koreans succeed in stem cell first

Announcement brings hope to scientists and sufferers, while opponents warn of race to clone babies

Tim Radford in Seattle and David Adam
Friday February 13, 2004
The Guardian

South Korean and American scientists have cloned human embryos and successfully extracted stem cells from one of them. The research opens the way for once-undreamed of treatments for long-term diseases such as diabetes, Parkinson's and Alzheimer's. It also reignites the simmering debate about human cloning.

The largely Korean team used 242 eggs from 16 women to clone 30 blastocysts -the tiny ball of cells that become an embryo. Stem cells are the agents that turn a single fertilised egg into up to 10 trillion cells in just nine months' gestation. Scientists around the world have cloned sheep, mice, rats, rabbits, horses, and even a mule. But despite dramatic yet unsupported claims from European fertility clinics, primates and humans were thought to be almost impossible to clone.

The Korean and US scientists sucked the original DNA out of the egg, and substituted it with chromosomes from an adult cell. Then they "tricked" the egg into thinking it had been fertilised.

"Nobody has cloned a human here," said Donald Kennedy, a biologist and editor in chief of Science, which publishes the study today, on the eve of the annual meeting of the American Association for the Advancement of Science in Seattle.

"All they have done is create a stem cell line from an early blastocyst ... To get from that to an embryo is a big step. A blastocyst of that stage could conceivably be used in an attempt to implant but we have no idea whether it would implant or not."

The achievement has inevitably sent ripples through scientific and political communities. In Britain, it was welcomed by the government's chief scientific adviser, Sir David King, and by the Royal Society. But anti-abortion groups warned that women may one day be used to "farm" donor eggs.

Dr Kennedy hoped that it might prompt American politicians to think again about the ban on using government money for such research. It could offer the possibility that people with degenerative diseases such as Alzheimer's could be given tissue transplants with their own genetic "signature".

"It may very well be that women with a substantial genetic predisposition or substantial concern about one of these might very well want to think about this. It is a long way away - a very long way away. What it offers is an interesting theoretical possibility which would be of use to a limited number of people on the face of the earth," Dr Kennedy said.

Yesterday's announcement was the culmination of years of research into the potential benefits of therapeutic cloning. But it is not the end of the story. For those benefits to be realised, researchers must now work out how to turn the cells into replacement human tissue needed to treat disease. Human stem cells have been available from embryos left over from fertility treatment for years, but it is not properly understood why one type of cell becomes heart tissue, and another liver.

Even the most optimistic researchers admit this means that reliable clinical applications are years away. Initially, the aim would be to culture large numbers of individual cells: islet cells to replace those that have failed in people with diabetes, or nerve cells that could be implanted in the brains of patients suffering from Parkinson's, Huntingdon's and Alzheimer's diseases.

In the long term, some scientists believe it could be possible to grow entire organs. Linda Kelly of the Parkinson's Disease Society said: "This announcement is clearly a milestone in medical research."

But pressure group Human Genetics Alert warned that researchers had given a big boost to those who want to make cloned babies. Such fears arise because the initial steps in therapeutic cloning and reproductive cloning are identical.

Britain was one of the first countries to ban reproductive cloning while allowing therapeutic cloning if researchers obtain a licence from the Human Fertilisation and Embryology Authority. No licences have yet been granted, though at least one is believed to have been requested.

**************************************

It's time hope triumphed

Ed Guiton explains why the Korean human cloning breakthrough will give hope to spinal injury victims everywhere

Friday February 13, 2004
The Guardian

When you leave a spinal hospital as I did, paralysed from the shoulders down, struggling to come to terms with the convulsion in your life, you find yourself repeating the mantra of spinal hospitals everywhere: "Put all thoughts of cure out of your mind."

My neck had been broken. Crucially, nerve cells of the spinal column are of a type that cannot regenerate unaided. The gap is filled with impenetrable scar tissue. "The way your body is functioning now," the doctors say, "is how it will remain for the rest of your life. Focus on looking after yourself, doing the best you can."

Until fairly recently they were probably right; there was no cure and spinal research was a career graveyard. Maybe it is better to get your hoping over quickly. Within hours of being shipped home to Britain from Bolivia where I broke my neck, I was told in a brutal fashion: "We'll get you off the ventilator, but that's it." My daughters were there, seeing me for the first time - they too had to cauterise hopes.

The problem with hoping that change will come sometime in the bearable future is that you might postpone the mental revolution required to live in the here and now. You will find little psychological help on hand to stop the screaming in your head. "When they come here from intensive care they are used to being pampered. We soon knock that out of them!" said one spinal-unit nurse to my wife.

But the world of scientific research on spinal injury has been turned upside down, for God's sake! This latest news, that the scientists in Korea have cloned foetal stem cells, gives great promise that soon it will be possible to harvest an immortal line of these marvellous cells that can turn into any tissue in the body. Of course, the matter of rejection has to be addressed. And it is not yet possible to produce a failsafe system for turning the cells into the material you require; they will often turn into extra scar tissue, which blocks the growth of nerve cells.

However, it is hard not to believe that at some point science will reconnect brain to body across the awful four-centimetre gap in the spinal column. In Australia, human clinical trials are going on right now in which a brew is injected into the spinal column to promote nerve growth and protect any existing nerve fibres .

This brew consists of an enzyme to digest scar tissue, a growth factor, and nerve cells from high in the nose that, unlike the stupid nerve cells in the spine, have not forgotten how to reproduce. (These are called OEGs, olfactory ensheathing glia). We are awaiting the Australian results. In China, however, a similar operation using OEGs derived from foetal material is already being offered commercially for $20,000 (£10,570), and more than 300 have been performed. So far results are promising.

Hope is no longer the option of fools but the prerogative of all with spinal injuries. And in the meantime one thing I have learned is that if you have a spinal injury you must fight for everything you need from the health and social systems; to hell with their budgets. Join up, join in, get out and about. To that degree the mantra is correct, life cannot be postponed, there may be no cure in your lifetime if you are in your 60s like me. But you are an adult, a citizen, you have a right to be told the truth and not be treated like some weak-minded idiot who will lose all perspective if asked to live with uncertainty.

There are about 50,000 spinally injured people in this country, not to mention the greater numbers who have multiple sclerosis and other nerve-related conditions. Once the new therapies come onstream there will be a great clamour for them, and for the physiotherapy that will keep us fit enough to benefit from them.

Acute hospitals and the research community should be walking in step with each other. And every effort must be made to overcome the fundamentalist scruples inhibiting US and European research on the use of embryonic stem cells.

If Christopher Reeve had been daunted by the pessimism pervading spinal injury research in the US, much of the progress now being made might never have come about. By raising millions he has transformed the whole field and drawn in new, young research scientists. Research grants are given only to those focusing on outcomes and - often to the dismay of scientists - sufferers from the condition have a vital say in who is supported. Research here should follow a similar path. It is high time that hope triumphed over resignation.