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Clone and Cloning: From Polly to Human?

In a lecture-preaching tour of England-Scotland in Oct.-Nov., 2002, we had the privilege and rare opportunity of visiting Roslin Institute in Edinburgh where Dolly was cloned in 1998. With recommendation by a university faculty member, we were cordially received by Dr. Tim King and given a tour of the labs, operation room, and the farm where sheep and cattle were kept under strict quarantine. Both Christine and I gently touched Dolly, Polly, Megan and Morag. Dr. King explained the lab work and procedures of how Dolly and Polly had been cloned by Drs. Ian Wilmut (attending a conference elsewhere) and Keith Campbell. In the following, I shall report on what we saw that day, the present status of cloning farm animals at Roslin Institute, and its implications in human cloning.

A. What is cloning?

So much confusion occurs when people see the word "clone and cloning." These words mean different things to different people. Scientifically and technologically, they refer to the following:

1. One group of genetically identical individuals/organisms descended from the same parent by asexual reproduction. Examples have been known for many years, such as potato tubers, strawberry suckers and onion bulbs used in their production/reproduction.

2. One group of genetically identical cells produced by mitotic division from an original cell. For example, chromosomes split into two daughter cells as seen in regeneration and replacement of bodily cells.

3. In bacterium or virus, the self-replicating DNA molecule is reproduced in vivo or in vitro, ending in two identical molecules.

4. The production of one or more genetically identical animals by "transferring the nucleus of a body cell (somatic cell and diploid) into an egg (not yet fertilized) with its nucleus or portion of its DNA previously removed so that the donor's nucleus or its DNA could replace the recipient's nucleus or DNA." This is known as nuclear transfer. The other way is by "splitting a reconstructed embryo (after fertilization) at 4-8 cell's stage," and then transplanting/implanting it into a surrogate mother. This is known as cell nuclear replacement. These two methods were used to produce Dolly and Polly at Roslin Institute.

We should confine any discussions of cloning to its specific scientific and technological meaning. As we know in life science, nuclear transfer is not a new technique; however, with Dolly and Polly, the technologies were employed in rather complicated and sophisticated ways and worked out with large farm animals.

B. Dolly, Polly, Megan and Morag's cloning and health:

In 1995, Drs. Wilmut, Campbell and associates produced Megan and Morag. In 1998, working with PPL Therapeutics, they cloned Dolly from the somatic cell (bodily, asexual) of a 6-year-old sheep. That was made known to the scientific community and general public and considered the breakthrough of the year. The event induced so much fascination and fanciful imagination.

It should be emphatically pointed out that the success rate was very low, averaging 1% with cloned embryos leading to live births. Unsuccessful attempts were not reported. Taken together, the rate should be much lower. Abnormal development of placenta was common, constituting the major cases of fetal loss earlier in pregnancy. Some cloned offspring died either late in pregnancy or soon after birth with cardiovascular dysfunction or respiratory malady. Cloned sheep or cattle were abnormally much larger in size. Even those that were apparently normal had unrecognized internal abnormalities or unable-to-register complaints. Luckily, Megan, Morag, Dolly and Polly survived, and they are still living to this date. Dr. King specifically points out that Dolly suffers from arthritis with muscle of the hind leg much weakened.

The colleagues at Roslin Institute admit that nuclear transfer is by no means a specific method of integrating the donor's DNA, or nucleus, into the recipient's. It requires an intact nucleus, with functioning chromosomes. DNA on its own is not enough. Another requirement is an appropriate supply of oocytes and surrogate mothers to carry the cloned embryos to term. After birth, the cloned animals experience various dysfunctions. Wilmus and Rudolf Jaenisch (MIT Biology Dept.) attributed all these to genetic instability and aberrant, unprogrammed gene expression (Science, March 30, 2001).

On July 6, in an article "Do not Clone Humans," they warned against unjustified extension to humans (Science, July 6, 2001). Turning deaf ears to the warning, Gibelli, T.B. and his colleagues at Advanced Cell Technology in Mass., produced/created three cloned human embryos (Scientific American, 286:44-51, 2002). It was lauded as a breakthrough by those who supported reproductive cloning or therapeutic cloning. The fact was that their cloned embryos developed only to the 2-, 4- or 6-cell stage. It was in an early stage of cloning, and it did not go any further. It suggested cloning human embryos could be far more difficult than in ruminants or mice. At any rate, the scientific community as well as the general public watches and awaits further news and conclusion.

Early in 2002, The National Bioethics Council, with Prof. Leon Kass of the Univ. of Chicago as Chairperson, voted and by consensus, submitted a proposal of moratorium for four years to President George W. Bush and the Congress. The reaction by the scientific community was a mixed bag. The US National Academy of Sciences sponsored a conference in August of 2002 on cloning. In the meeting, Drs. Wilmut and Harry Griffin vehemently opposed the attempt on cloning humans by a consortium of Drs. Severino Antinori of Italy and P. Zavos from Kentucky. These gentlemen had been for years involved in a very lucrative industry, i.e. in vitro fertilization for infertile parents. They made extravagant claims of how they were going to avoid such risks in human cloning. They were far more comfortable in talking of their program with news media. It turned into a media circus! The media indeed paid too much attention to their claims. Scientists attending the conference were extremely frustrated and disgusted at Antinori's unwillingness to acknowledge the risks and to provide any scientifically sound evidence. In a free society, nobody could do any more, and nobody was in a position to stop them.

This is where we stand today.

C. Ethics and our Christian stand:

In the last five years, with nuclear transfer or reconstructed embryo-splitting, scientists have cloned mice, goats, pigs, sheep and cattle, and failed with cats, dogs, rats, rabbits, and monkeys. Likely, in the coming years more animal species will be cloned, but improving success is by no means easy to come by. The high incidence of abnormalities is not surprising. There are so many intricate and interlocking molecular mechanisms that cannot be duplicated with/by human ingenuity. Scientists with their know-how can only reach approximated conditions of God's creation at cellular level; they can go no further.

With farm animals, no ethics or rights have been debated. As an academician, scientist and Christian, I believe that cloning humans is altogether different. A human is created in God's image. He is unique. Even his soul and genome are unique. Life begins at conception. Christians and the Church must uphold the sanctity of human life. We must accept these dogmas and take our stand. Scientific and biotechnological advancements, taken as instruments and service for humankind, only confirm our convictions and reinforce our stand: God is the Creator, and life comes from His creation.

(Stephen C. Y. Liu is Prof. Emeritus of microbiology and molecular biology, and church elder, residing in Ann Arbor, Michigan. His e-mail address is stephen_c_y_liu@yahoo.com)

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