"THE MEDICAL ESTABLISHMENT HAS BECOME THE MAJOR THREAT TO HEALTH." - Ivan Illich (medical historian), in Limits to Medicine, 1976

SHEEP "PHARMING" IN MIDLOTHIAN

Clone: [Greek. klon, slip, cutting used for propagation; A colony or group of organisms (or an individual organism), or a colony of cells derived from a single organism or cell by asexual reproduction, all having identical genetic constitution; To produce such a colony or individual.] Steadman’s Medical Dictionary

This year, the ‘creators’ of Dolly, the cloned sheep, have been challenged and their paper published in Nature, reporting her birth, criticised as "an anecdote, not a result"1.

Dr. Ian Wilmut and his colleagues from the Roslin Institute reported that Dolly’s ‘biological mother’ was a single cultured cell from the udder of a six-year-old pregnant Finn Dorset ewe. The nucleus of this cell was introduced by cell fusion into the egg of a Scottish Blackface ewe from which the nucleus had been removed. After culturing for a few days, the egg was transferred to a surrogate mother, another Scottish blackface ewe. Eventually, of 277 similar fusions, a single live lamb was born – number 6LL3. She was christened Dolly, after Dolly Parton – a schoolboy level reference to her mammary cell origin. That Dolly displays the characteristics of her breed, not those of her surrogate mother or the egg donor is regarded as proof that she is the clone of the Finn Dorset ewe.2

Dolly was not the first lamb to be cloned by the Roslin Institute – the births of Megan and Morag, two Welsh mountain lambs, were reported in Nature in 1996, almost a year before Dolly3. What makes her special is the fact that she is the first to be cloned from an adult cell using nuclear transfer technology. In the experiment that produced Dolly, seven other lambs were born but these, like Megan and Morag, were derived from embryonic and foetal cells of sheep of other breeds.2

The critics, Sgaramella and Zinder, suggest that there was a mix-up and Dolly came from a foetal or stem cell.1 Wilmut argues that a mix-up of cell cultures was unlikely but admits a slight possibility that a foetal cell from the pregnant ewe could have been the source of Dolly’s DNA. A sample of this is to be compared with Scottish Blackface DNA and with DNA from the frozen mammary cells. Other cloning researchers have supported Dr Wilmut, describing a single live birth out of 277 attempted fusions as a "very respectable result", not an anecdote and that repeating the experiment would be costly4.

Exciting (or not) for scientists as the cloning of Dolly may be, she has no commercial use. PPL Therapeutics, the biotechnology firm that collaborated with the Roslin Institute to produce her, is in the business of biopharming – its aim is to create a flock of identical sheep, or preferably cows, that produce human proteins in their milk5.

To this end, another sheep, Polly, was born last year. The human gene that produces a blood-clotting factor, factor IX, was introduced into the nuclei of foetal cells from Poll Dorset sheep. Again using nuclear transfer technology, these cells were fused with donor eggs and transplanted into surrogate ewes. Polly was the first of three live births (all clones) carrying this human gene6.

The creation of transgenic animals with human genes is not new. Previously, human DNA was micro-injected into fertilised eggs and the success rate only became evident after birth. Nuclear transfer is far more efficient, allowing selection of the cells that express the inserted gene before fusion with the egg. PPL took many years to build up a flock of 600 transgenic sheep, as only 4% of lambs expressed the gene of interest. Now, transgenic animals can be cloned to produce large numbers of identical animals all expressing the same human gene5.

Sheep are not the only animals to have been cloned. An American company has recently cloned a calf – Gene – from a foetal cell. A company spokesman says that cattle can be cloned with desirable traits – high milk production or tender meat. There is also the potential to produce clones that secrete pharmaceuticals in their milk7. The Japanese too claim to have cloned calves8. A group in Oregon has taken the first steps towards cloning monkeys. The researchers took two 8-cell monkey embryos, separated the cells and then transferred cells from the embryos into cells without a nucleus. The two monkeys are not clones as they are derived from two different embryos, however, the potential for producing clones is there9. And this takes us a step further toward cloning humans, an eventuality which horrifies many.

Farming becoming pharming raises serious animal welfare issues. Donor animals must undergo surgery to obtain eggs; many attempts are required to produce a single live birth; cloned animals often have abnormally high birth weights; foetuses may be malformed; and foreign genes may have harmful effects on the health of animals10,11. 

Some believe that the creation of herds of identical clones is simply an extension of selective breeding to enhance desirable genetic traits. Others maintain that we exploit farm animals anyway by eating them and using their skins or wool, so why not go one step further and find yet another means of utilising them. The use of animals as living factories is distasteful to most of us. For many years human proteins have been produced in genetically-engineered yeasts and bacterial cells, without causing animals to suffer13. Of course, this technique is less productive and more costly … but should we value the profits of pharmaceutical companies above lives?

Finally, how’s Dolly getting along? The media star who last year had her fleece donated to help raise funds for cystic fibrosis research14 gave birth to Bonnie on 13th April 199816. 

This article appeared in the NAVS (National Anti-Vivisection Society) Magazine "The Campaigner" Jan-Jun 98. For further information contact NAVS 261 Goldhawk Road, London UK W12 9PE. Ph: 0181-846 9777 - Fax: 0181-846 9712. Email: navs@cygnet.co.uk - WebSite: http:/www.cygnet.co.uk/navs.

References:

  1. Sgaramella V and Zinder ND (1998) Dolly Confirmation. Science 279: 635-636.
  2. Wilmut L et al (1997) Viable offspring derived from fetal and adult mammalian cells. Nature 385: 810-813.
  3. Campell KHS et al (1996) Sheep cloned by nuclear transfer from a cultured cell line. Nature 380: 64-66.
  4. Butler D (1998) Dolly researcher plans further experiments after challenges. Nature 391:825-826.
  5. Pennisis E (1998) After Dolly, a pharming frenzy. Science 279: 646-648.
  6. Schnieke A et al (1997) Human factor IX transgenic sheep produced by transfer of nuclei from transfected fetal fibroblasts. Science 278: 2130-2133.
  7. Pendick D (1997, 16 Aug) Clones unlimited. New Scientist 155 (2095): 11
  8. SCRIP no 2258 August 15th 1997 p17
  9. Bradbury J (1997) First Dolly the sheep, now multiple monkeys. The Lancet 349: 705.
  10. Gordon M (1997, 26 Apr) Suffering of the lambs. New Scientist 154 (2079): 16-17
  11. Government advisors investigate cloning … Agscene Spring 1998 p17
  12. Cloning and Farm Animal Welfare. Comments to: The Farm Animal Welfare Council from Compassion in World Farming
  13. Government backs genetic engineers’ blood problems (1981, 17 Dec). New Scientist 92 (1284): 785
  14. The Daily Telegraph 21st may 1997
  15. Dolly’s baby (1998, 17 Jan). New Scientist 157 (2117): 7
  16. Dolly had a little lamb … The Independent 24 April 1998

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