Well Hello Dolly........It's so nice to have you around....
   
Dolly Levi, the match-maker extrodinnaire, what have you wrought.

First a few definitions.......... to frame a discussion

clone ...... is a population of genetically identical organisms, all derived from a single individual by asexual reproductive methodology. Clones have been commonplace in plant horticulture since ancient times. All individual MacIntosh apple trees, for example, are members of a clone, having been derived initially from a single mutated plant, and they all share identical genes. A vast array of fruit and nut tree varieties and innumerable ornamental plants represent clones.

     During the second half of the 20th century, techniques for cloning animals were successfully demonstrated in amphibians by such researchers as Briggs and King (Proc. Natl. Acad. Sci. 38:455, 1952) and J.B. Gurdon (Oxford Univ. Press, 1974), and by plant scientists at Cornell University (F.C. Steward). The nucleus of an amphibian egg cell (haploid) was replaced by that of an adult epithelial cell (diploid). The egg cell is then stimulated to develop without fertilization, and the resulting embryo is composed entirely of cells genetically derived from the single implanted adult nucleus.

     In the 1980s recombinant DNA technology provided another means of cloning genes; the new technology allowed researchers to transfer, manipulate, and change genes. A most significant limiting factor in the development of this technology has been establishing an effective means of transferring altered genes into recipient embryonic cells. Research has centred on the use viruses, bacteria, and plasmids as vectors for transferring genes. The possible applications of recombinant DNA technology for commercial and scientific purposes are many. The potential exists for large-scale and inexpensive production of proteins and other biosynthetic products by gene cloning. Examples of active areas of research are in the development of insulin, the antiviral agent interferon, and vaccines such as that for the hepatitis B virus.

     The practical applications of cloning are economically promising but philosophically unsettling. Animal breeders would welcome the chance to clone top-quality livestock. A single superior animal (one that produces leaner meat in greater quantity) could be used to create a line of genetic constancy, much as has been done with fruit trees. Clones are also highly useful in biological research because of their genetic uniformity.

     The cloning of human beings is a subject fraught with ethical and moral controversy. The phobias raised by hollywood movies as "The Boys from Brazil" have frightened a mis-informed public into believeing that duplicates of Hilter or Einstein are possible. Additionally, if cloning can ensure the infinite replication of specific genetic traits, a judgment would need to be made as to which traits are desirable and therefore worthy of perpetuation. The persons empowered to exercise such judgment would be in a position to change the course of human development.

 

    Some recent news items pertaining to the cloning of Dolly .........
genetic engineering ........ the artificial manipulation, modification, and recombination of DNA or other nucleic acid molecules in order to modify an organism or population of organisms.

eugenics....... the study of human improvement by genetic means. Proposals for ameliorating undesirable qualities of the human race date from ancient times. Plato's Republic depicts a society in which there is an effort to improve human beings through selective breeding. The first thorough exposition of eugenics, however, was made by the English scientist Francis Galton, a pioneer in the use of statistics. In his book, Hereditary Genius (1869), Galton proposed that a system of arranged marriages between men of distinction and women of wealth would eventually produce a gifted race. He coined the term eugenics in 1883 and continued to expound its benefits until his death in 1911.

     The American Eugenics Society, founded in 1926, supported the proposition that the wealth and social position of the upper classes was justified by a superior genetic endowment. U.S. eugenists also supported restrictions on immigration from nations with "inferior" stock, and argued for the sterilization of insane, retarded, and epileptic citizens in the United States. As a result of their efforts, sterilization laws were passed in more than half of the U.S. states, and isolated instances of involuntary sterilization continued into the 1970s. The assumptions of eugenists came under sharp criticism beginning in the 1930s and were discredited after the German Nazis used eugenics to support the extermination of Jews, blacks, and homosexuals.

     Since the 1950s there has been a renewed interest in eugenics. Because certain diseases (e.g., hemophilia and phenylketonuria - to be discussed by the class later in the semester) are now known to be genetically transmitted, couples can choose to undergo genetic screening, in which they learn the chances that their offspring might be affected by some combination of their hereditary backgrounds. Couples at risk of passing on genetic defects may opt to remain childless or to adopt children. Furthermore, it is now possible to diagnose certain genetic defects in the fetus. Couples could choose to terminate a pregnancy that involves a genetically disabled offspring. These advances in human reproductive genetics have reinforced the eugenic aim of identifying and eliminating undesirable genetic material. Counterbalancing this trend, however, has been medical progress that enables victims of many genetic diseases to live fairly normal lives. Genetic surgery, in which harmful genes are altered by direct manipulation, is also being studied, and, if perfected, could obviate eugenic arguments for restricting reproduction among those who carry harmful genes. Such conflicting innovations have complicated the controversy surrounding eugenics. Moreover, suggestions for expanding eugenics programs, which range from the creation of sperm banks for the genetically superior to the potential cloning of human beings, have met with vigorous resistance from the public, which often views such programs as unwarranted inteference with nature or as opportunities for abuse by authoritarian regimes.

THE START OF SOMETHING BIG? Dolly becomes a new icon for science.

News and Analysis : SCIENTIFIC AMERICAN, May 1997 page15

"It was supposed to be impossible. When Ian Wilmut, Keith H. S. Campbell and their colleagues at the Roslin Institute near Edinburgh, Scotland, announced in February that they had cloned an adult sheep, creatating a lamb with no father, they did not merely stun a world unprepared to contemplate human virgin births. They also startled a generation of researchers who had grown to believe that cells from adult vertebrate animals cannot be reprogrammed to make a whole new individual. Dolly, the lamb at the epicenter of the culture-shock waves, developed from a sheep egg whose original nucleus had been replaced by a nucleus from an adult ewe's udder. The trick that other had not thought of was that of starving the donor cells for five days before extracting their adult nuclei. Wilmut and Campbell realized that this made the nuclear DNA susceptible to being reprogrammed once placed in an egg.

     Dolly's birth presents an ethical and scientific watershed. Around the world, advisory committees and legislators are frantically trying to decide whether and when it might be ethical to duplicate the feat in humans. Traditional teachings that life begins at conception suddenly seem to be missing the point. "We have to rid our minds of artificial divides," says Patricia King of Georgetown University. President Bill Clinton quickly announced a ban on the use of federal funds for human cloning research and asked the National Bloethics Advisory Commission to recommend some actions.

     Many animal development experts now suspect that genetically duplicating humans is possible, especially as Donald Wolf of the Oregon Regional Primate Research Center has already cloned rhesus monkeys from embryonic cells. (Cows, sheep and rabbits have also been cloned from embryonic cells in recent years, but these experiments lacked the emotional impact of a copied mature animal.) lndeed, it took less than two weeks from the date of the Roslin Institute's announcement in Nature for Valiant Ventures in the Bahamas to announce that it will build a laboratory to clone people willing to pay. The company was founded for this purpose by the Raelian Movement, a self-styled religious organization.

      But producing healthy human clones may prove to be extremely difficult. Wilmut, who argues for a moratorium on such attempts, points out that more than half the cloned sheep pregnancies he initiated failed to develop to term. Some had abnormalities. "People have overlooked that three out of eight [cloned] lambs died soon after birth" in an earlier study, he notes. Moreover, it took 277 attempts to produce Dolly from an adult cell.

     Should Valiant Ventures's plans ever come to fruition, they would probably produce many unhappy customers and some dead babies before they created a live one. That grim scenario prompts bloethicist Arthur Caplan of the University of Pennsylvania to argue that anyone attempting such a project "ought to be arrested." He predicts that a moratorium will be enforced by government officials. (Such restrictions might spare egotistical millionaires the disappointment of learning that cloned offspring can be just as hard to handle as natural ones.)

     Wilmut concurs that there are no ethical grounds to justify duplicating existing humans. He even opposes allowing a couple to copy a child in order to get a source of tissue to save its life (although some years ago a California couple conceived a child in the time-honored manner to supply bone marrow for a sibling). The only human cloning Wilmut would condone is copying an embryo to avoid genetic disease caused by mutations in mitochondria, energy producing organeeles, lying outside the cell nucleus, with their oen DNA. Mutations of mitochondrial DNA can cause devastating afflictions, including blindness. By implanting a nucleus from an embryo with defective mitochondria into an egg donated by a woman with healthy mitochondria, researchers could help a couple have a child free from mitochondrial disease.

     Other bioethicists are more receptive to copying people. John C. Fletcher of the University of Virginia believes that society might find it acceptable for a couple to replace a dying child or for a couple with an infertile partner to clone a child from either partner. "I am not scared of cloning," Fletcher declares. The widespread squeamishness toward embryo research suggests, however, that Fletcher may for now be in a minority.

     Four years ago the revelation that researchers at George Washington University had microscopically divided genetically defective human embryos and provoked a national outcry-even though the investigators never contemplated implanting the multiple embryos into a uterus. Last year the National Institutes of Health terminated an employee who used federal equipment to perform genetic tests on cells from human embryos before implanting them, in violation of a congressional ban.

     In the fields of animal husbandry and biomedicine, cloning could bring about big changes-provided the technique works in species other than sheep and can be made more efficient. "I have no doubt this will become the method of choice for producing transgenic animals," says James M. Robl of the University of Massachusetts. Transgenic, or genetically manipulated, animals are typically now made by a laborious hit-or-miss procedures that involves injecting genes into eggs and breeding the few animals that take up the genes. Cloning should expedite the rapid generation of large numbers of creatures with specific alterations, Robl believes.

     Robl founded a company, Advanced Cell Technology, that plans to clone transgenic animals that will produce human proteins in their milk or supply tissue for transplants that human immune systems will not reject. (The Roslin Institute has a partnership with PPL Therapeutics, which will also produce animals that secrete human proteins.) Robl foresees large gains for animal breeding in general. Experiments involving genetically identical clones, he explains, would involve fewer confounding variables and thus should be easier to interpret; moreover, fewer animals may be needed to produce the same results. Breeding programs to rescue endangered species might also become more effective. Cloning could sidestep some of the difficulties of sexual reproduction, although by limiting genetic diversity it might create its own problems.

     Looking toward more distant shores, Dolly's existence raises the question of whether cells from patients can be reprogrammed to make genetically compatible therapeutic tissue, such as brain tissue of the type that is destroyed in Parkinson's disease. "The components needed for this kind of manipulation are out there," Robl speculates.

       In the meantime, there is much to learn about the potential of genetic reprogramming. Nobody knows whether Dolly will live a healthy life, because her cells may in some respects behave like those of an animal six years old-the age of Dolly's parent when she was copied. It will be scientifically fascinating, if Dolly develops strange and fatal afflictions in midlife. It will be even more fascinating if she does not. "

-Tim Beardsley in Washington, D.C. SCIENTIFIC AMERICAN May 1997 -

 

 


Human clones could not be exact copies say experts.... By Joanne Kenen

WASHINGTON (10:47am ET 03/16/97 Reuter) - As society debates the ethics of cloning, scientists and ethicists say it is important to understand that cloning a human being could never produce an exact duplicate. Everything from the cytoplasm of the egg cell where the DNA genetic blueprint is placed, to whether a cloned person remembered the Beatles would impose individuality on ''borrowed'' DNA.

Even identical twins, who are nature's clones, are not totally identical. Clones made in a laboratory would be twins born years or decades apart, separated by generational and cultural chasms.

"By far the most mischievous misunderstanding is this idea that you can Xerox people,'' said Harold Shapiro, president of Princeton University and chairman of the National Bioethics Advisory Committee which President Clinton has asked to evaluate the legal and moral dimensions of cloning. "If you lost a child or parent, and wanted to bring a person back -- you can't do that,'' Ian Wilmut, the scientist who cloned a sheep in Scotland, told a U.S. Senate panel last week.

Many experts, including Wilmut, are deeply troubled by the idea of cloning humans, a technology that could transform reproduction into replication; that could turn a parent and child into a pair of identical twins. 'If you take the DNA and, 20 years later, you put it in a different uterus, you couldn't possibly replicate a person,'' said Harvard University medical ethicist Lisa Geller. 'And if that's what you're trying to do, to replicate a person -- you're going to have a hell of a hard time with a teenager,'' she added.

Ethicists, geneticists, biologists and psychologists argue endlessly about the balance of "nature'' and "nurture'' in human development, about which traits are inborn and which are shaped from environment and experience. But even those experts tilting toward the 'nature'' end of the spectrum, like psychologist Thomas Bouchard of the well-known University of Minnesota Center for Twin and Adoption Research, say human clones would look alike, but would not necessarily be alike.

"The difference in temporal experience would magnify the difference in personality,'' said Bouchard, who believes about half of psychological tendencies are inherited.

Environmental factors come into play from the very start. The cytoplasm of the cell into which the DNA is placed will be different from the adult cell from which it is derived. Small pieces of genetic material, known as mitochondrial DNA, will also be distinct.

And once the clone is implanted into a womb, the prenatal environment will differ as well. The diet of the woman carrying the fetus, whether she smokes, what chemicals or toxins she encounters in her daily life all affect the child. "Identical twins are usually brought up roughly together, and treated in similar ways. But if the clone and source differ by a generation ... all kinds of things change over a generation, what's allowed, what's taught, our diet,'' said Philip Kitcher, a philosopher at the University of San Diego and the author of "The Lives to Come: the Genetic Revolution and Human Possibilities.''

A clone of Albert Einstein, taken out of 19th century Germany and placed, for instance, in late 20th century southern California would probably still be smart, and may well have the same wild white hair. But he would not necessarily become a physicist.

A clone of Michael Jordan would probably be tall, agile and have lightning reflexes. But he might not become a professional basketball player. And a clone of any ordinary man or woman might look almost indistinguishable from the genetic parent, but could have a whole different view of the world, based on experience, luck or what theologians would call soul.

"Dolly (the cloned sheep) is a snapshot -- not a snapshot of an adult sheep but one of that sheep's cells,'' said University of Pennyslvania bioethicist Glenn McGee.

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Dolly scientists reject human cloning ........ By Patricia Wilson

WASHINGTON (03:33 PM ET 06/25/97, Reuter) - The scientists in Scotland who cloned Dolly the sheep have been approached by two families seeking to use the technique to produce exact genetic copies of relatives, the team's leader said Wednesday. He made it clear the two requests had been rejected. "I can't think of any embryologist I know who would be interested in cloning a human being,'' Dr. Ian Wilmut told a news conference at the American Association for the Advancement of Science.

"One inquiry was from a lady shortly to lose her father and the other was from a couple who lost their daughters in an automobile accident,'' he explained, without saying where the requests had come from.

Despite fears that the idea of cloning an existing human being from his or her DNA might take hold among the bereaved, the famous, or the scientifically curious, Wilmut said those were the only two inquiries he had received.

Wilmut and his team amazed the world when they announced in February that they had cloned a lamb -- which they named Dolly -- from a single cell taken from an adult sheep. Their success was so controversial, raising the prospect that the procedure could be used to make humans genetically identical to an existing man or woman, that President Clinton almost immediately appointed a commission of scientists, lawyers and theologians to review the legal and ethical ramifications of cloning.

The group was faced with trying to reconcile the views of opponents of cloning who regard it as an affront to nature and demand a complete ban, and supporters who see it as a stunning scientific breakthgrough with promising medical repercussions.

Their solution was to propose a five-year ban on cloning a human being, but to allow the cloning of human embryos for private laboratory research. Clinton proposed legislation embodying those recommendations June 9.

Wilmut said he fully supported Clinton's plan. "I share the concern, almost universal, that this technique should not be misused ... it should not be used to produce a copy of a person who is already here,'' he said.

But Wilmut and Dr. Ezekiel Emanuel, associate professor of medical ethics at Harvard Medical School, acknowledged rumors -- which they said they could not substantiate -- that some people had expressed keen interest in cloning a human.

"The reasons should be obvious -- being first, the money,'' Emanuel told the AAAS news conference.

As for Dolly, Wilmut said the sheep was perfectly healthy and would be given a chance to breed in the fall. ``I have nothing to report. She's in no way different from any other sheep,'' he added.

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Clinton proposes five-year ban on human cloning ....   By Arshad Mohammed

WASHINGTON 02:20 PM ET 06/09/97(Reuter) - President Clinton Monday proposed a five-year ban on cloning a human being, saying it was morally unacceptable and could undermine society's respect for human life.

            Announcing the proposal at the White House, Clinton said the legislation would not prohibit the cloning of human DNA or of animals, arguing this did not pose the same moral questions and could lead to great medical and agricultural advances.

            In proposing the law, Clinton accepted the findings of an  ethics commission which he asked to review the legal and ethical
ramifications of cloning after scientists in Scotland reported in February they had cloned a lamb -- which they named Dolly --
from a single cell taken from an adult sheep.

            ``One unanimous conclusion has emerged: attempting to clone a human being is unacceptably dangerous to the child and morally unacceptable to our society,'' Clinton said in a White House Rose Garden ceremony to announce the legislation.

            ``What the legislation will do is to reaffirm our most cherished beliefs about the miracle of human life and the
God-given individuality each person posesses,'' he added.

            ``It will ensure that we do not fall prey to the temptation to replicate ourselves at the expense of those beliefs and the
lives of the innocent children we would produce,'' he said.

            Under the proposed legislation, which would have to be passed by the Republican-controlled Congress, cloning a human
being would be prohibited for five years.

            Violating the law could lead to fines of $250,000 or twice the gain or loss a scientist might make from the endeavor.

            While the legislation is pending, Clinton said the ban on using federal funds to clone humans would remain in effect and
he called on the private sector to voluntarily refrain from the technique, known as ``somatic cell nuclear transfer.''

            If the bill were signed into law, the National Bioethics Advisory Commission, which is chaired by Princeton University
President Harold Shapiro, would have to report 4 { years later on whether the overall ban should be continued.

            The advisory commission of 18 scientists, lawyers and theologians sought to reconcile the views of opponents of
cloning who regard it as an affront to nature and demand a complete ban, and supporters who see it as a stunning scientific
breakthrough with promising medical repercussions.

            Polls taken shortly after the announcement of the cloning of Dolly showed 90 percent of Americans opposed human cloning.

            In his remarks, Clinton stressed the moral dangers of cloning children.

            ``Creating a child through this new method calls into question our most fundamental beliefs. It has the potential to
threaten the sacred family bonds at the very core of our ideals and our society,'' he said. ``At its worst, it could lead to
misguided and malevolent attempts to select certain traits, even to create certain kind fo children -- to make our children
objects rather than cherished individuals.''

            But he insisted that cloning human DNA and animals did not pose the same moral questions.

            ``There is nothing inherently immoral or wrong with these new techniques used for proper purposes ... In fact they could
hold the promise of revolutionary new medical treatments and life-saving cures to diseases like cystic fibrosis, diabetes and
cancer, to better crops and stronger livestock,'' he said.

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Scientists grow monkeys from cloned embryos
 
Web posted at: 9:00 p.m. EST March 2, 1997
 
PORTLAND, Oregon (CNN) -- Scientists have produced sibling rhesus monkeys from cloned embryos in the technology's closest application yet to a species related to humans.  (800K/23 sec. QuickTime movie)

The monkeys were developed using cells from different embryos, so they are not genetically identical, said Don Wolf, senior scientist at the Oregon Regional Primate Research Center.

"I don't see it as nearly as big a step as the step that was announced last week in [the magazine] Nature," Wolf said, referring to a Scottish lab's successful cloning of an adult sheep.
 
But the monkey experiment does mean the technology for producing genetically identical animals is now available, and that promises to be useful in experimental studies on diseases and "nature versus nurture" theories, he said.

Conducting tests on genetically identical animals will help reduce the number of animals needed for an experiment to have statistical significance, he said.

Wolf told the Portland Oregonian newspaper the experiment technically was not cloning.

"That is not what I am calling it," Wolf said. "Cloning in the strict sense of the term is using an adult cell so you get an exact replica of the adult. That is not what we are doing."
 
On the "down side," the achievement takes science closer toward suggesting the genetic procedure called nuclear transfer can be done in humans, he said.

"Of course, we have absolutely no interest in even cloning an adult rhesus monkey, let alone to be involved in cloning in humans," Wolf said, adding he finds the idea "repugnant."

The nuclear transfer technology has already been applied to mice, rabbits, cows and pigs, among other animals, said Wolf, who is also is director of the human in vitro fertilization laboratory at Oregon Health Sciences University.

To develop the monkeys, scientists harvested eggs from an adult female monkey, then fertilized each of them in vitro. After about three days, the embryos divided to the eight-cell stage of development.

The scientists then teased apart the cells, taking one full set of chromosomes from each embryo cell and inserting it into a fresh egg stripped of its DNA.

Nine successfully developed into embryos and were implanted in adult females. Three pregnancies and two live births resulted.

A paper on the work, titled "Nuclear Transfer in Rhesus Monkeys," has been submitted to the journal Biology of Reproduction but had not yet been accepted, Wolf said.

The Associated Press contributed to this report.                          back



Dolly the cloned sheep mates
Is Dolly a mom-to-be?

January 8, 1998 - Web posted at: 6:42 p.m. EST (2342 GMT)

EDINBURGH, Scotland (AP) -- Dolly the cloned sheep has been mated -- the old-fashioned way -- but there's no word yet on whether she's expecting.

Scientists at Edinburgh's Roslin Institute, who made history when they cloned Dolly from the cell of another sheep's udder last year, insisted Thursday that there won't be any scientific interference.

"Dolly has been mated and we will wait for nature to take its course," said Dr. Harry Griffin, the institute's assistant director. "We don't know if she is pregnant yet."

Staff at the institute said in September that Dolly would be bred with a ram early this year to determine whether she is fertile and can produce healthy lambs.

Dolly, now 18 months old, is a Finn Dorset breed. She is the first mammal cloned from the cell of another adult mammal.
Graeme Bulfield, the institute's director, said the breeding will determine whether Dolly's lambs would be affected by her unusual conception. Her offspring would not be clones and would be genetically different from her, he said.

Healthy lambs would mean that the cloning process had produced a fully healthy, fertile sheep, which would be valuable knowledge for PPL Therapeutics, the Scottish biotechnology company formed to market the center's work, Bulfield said.
The institute already has proven that cloned animals can reproduce.

Megan and Morag, sheep conceived through a different cloning process, have lambs of their own.
Griffin was quoted as telling the Evening Standard that the institute is planning a new center where it can put Dolly, Megan, Morag and Polly, a lamb carrying a human gene, on public display. He said it should be open by Easter.

Copyright 1998 The Associated Press. All rights reserved. This material may not be published, broadcast, rewritten, or redistributed.
 

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copyright c1997, Charles Mallery, Department of Biology, University of Miami, Coral Gables, FL 33124
Last Update - 5 January 1998