Science in Society Archive

Xenotransplant Fails All-round

A key paper [1] was published in the middle of a storm of bad publicity over the safety of xenotransplantation (See Xenotransplantation Must End, this issue), and by Imutran and Infigen, describing a cloning procedure for pigs using in vitro fetal cell culture that have been genetically modified.

The experiment was heralded by the authors as a 'reproducible methodology enabling strategies for GM pigs for xenotransplantation, the production of pharmaceutical proteins (biopharms) and the enhancement of pig breeding programmes'. They claim it is the most promising technology for achieving targeted knockout of porcine endogenous retrovirus (PERV). The aim was to produce 'humanised' organs from GM cloned pigs that could resist rejection and be used in xenotransplantation.

Despite the hype, there is no escaping the massive failure rate in this experiment, nor the displeasure of Imutran's parent company, Novartis, which have since shut down the whole operation and merged Imutran with Biotransplant.

Pig fetal cells were cultured and genetically modified with a vector containing an antibiotic resistance marker gene. About one thousand nuclei from these cells were transferred, one by one, or cloned into pig oocytes and placed in an embryo culture for three days prior to in vitro fertilization. Twenty-three recipient sows were used in total, each received between 115-160 embryos! (What happened to the poor sows.) Despite these massive efforts, the rate of pregnancy initiation was 30%, 7 out of 23 recipients, and only 2 litters each containing 2 piglets were born. The second litter died after one week.

A subsequent letter published in in the same journal by the president of Infigen said, "due to unfortunate circumstances in managing an unruly first time mother the second litter of cloned piglets were lost." The 2 piglets were taken away from their mother and lost significant body weight, which caused their death.

Having come from a long line of farmers myself, I find this statement hard to believe as piglets are often taken from unruly first time mothers and easily bottle fed, especially when they cost millions of dollars to produce!

  1. Jeff Betthauser et al Production of cloned pigs from in vitro systems. Nature Biotech:2000:
  2. Bishop MD Pig litter update. Nature: 2000: 18: 1227.

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