The arrival of Dolly, the cloned Scottish sheep that was an exact genetic copy of her mother, was regarded as a major scientific breakthrough. Dolly was generated by cloning technology using a cell from the udder of an adult animal (her mother).
Dolly was not only scientifically important, but heralded what promises to be a revolution in the animal biotechnologies, such as embryo multiplication, cloning and transgenics.
It is useful to understand several terms now being used in discussions on animal biotechnologies.
• Embryonic cells are cells in the embryo that have not progressed down any particular pathway to form tissues such as muscle, skin, heart, nerves etc. The term Embryo Multiplication (EMT) can be used when embryonic cells have been multiplied by nuclear transfer. EMT is just a type of cloning using embryonic cells.
• Somatic cells on the other hand refers to cells that have differentiated (or specialised) into specific cell types (such as skin, muscle etc.) after implantation, but which are not germ cells. Germ cells refer to the sperm, ova or their precursors. Thus the term somatic cell refers to almost any cell in the body of the foetus, newborn or adult animal, apart from germ cells.
• Nuclear transfer, Cloning and EMT (see diagram below) all refer to the fusion of a cell, either embryonic or somatic, with an egg (oocyte) that has had its nucleus containing the genetic material removed (a process called enucleation). The product of this fusion event is a single cell embryo, which then begins dividing again from the one cell stage (as with a normal embryo after fertilisation).
Producing genetically identical embryos by nuclear transfer (from Cattle Breeding Technologies, Genetics Australia, 1996).
• Transgenic. The genetic make up of a cell can be modified either by putting in a new gene (from another animal, human or plant, or even a synthetically produced gene) or removing ("knocking out") an existing gene. The modified cell, or animal composed of such cells, is said to be transgenic, or genetically modified.
The possibilities for human health
In human health there are some very significant possibilities, including:
• the production of valuable human medicines in the milk of cows, sheep or goats
• the development of animals (e.g. pigs) whose genetic makeup has been slightly modified so that their organs (heart, kidney etc.) can be transplanted into humans whose organs have failed, without being rejected ("xenografts").
The possibilities for agriculture
In 1991 Genetics Australia made the decision to invest considerable resources into a program targeting Embryo Multiplication and Transfer (EMT) as the means of producing genetically identical animals at low cost.
This decision was based on an assessment that there would be breakthroughs in cloning technology sometime in the future. An important risk of not investing was that Australia would be left well behind in technology developments for genetics, that had the potential to place Australian dairy farmers at an international disadvantage compared to competitors.
The close collaboration developed between Monash University and Genetics Australia now provides Australia with a capacity in cloning technologies. The development of a fully functioning in vitro production laboratory at Genetics Australia gives the cooperative the capacity to contribute directly to the research and provides a commercial focus for the program.
Commercialisation
Since Dolly's arrival, the pace of progress has been swift. Huge amounts of dollars are being invested, particularly by pharmaceutical companies interested in developing applications for human health.
For example, one human protein that lends itself to such production in transgenic animals is human serum albumin (HSA).
The annual global requirement of HSA is in the order of 500 tonnes, worth US$1.5 billion. This is currently extracted from human blood by expensive technology, with severe limits to supply. It is estimated that the set-up cost to produce these human proteins by traditional "synthetic" technology is around US$200 million. By comparison the cost of making one transgenic "founder" animal producing such proteins in the milk is around US$500,000.
An insight into the future
At the recent International Embryo Transfer Society Conference in Boston during January two examples of the application of advanced animal breeding technologies were announced. Ian Lewis points out that these examples give us some insight into why these technologies are important and why they are likely to develop at a rapid rate.
George and Charlie
George and Charlie are a couple of healthy bull calves. However they are not just any old bull calves.
Firstly, they are cloned. The cells from which they were cloned came from cells from a bovine foetus.
Before the cells were used in the cloning process, they were genetically altered.
To top it all off, this pair of bulls came from cells from the same foetus, which means that they are genetically identical.
Therefore George and Charlie are identical, transgenic, cloned bull calves, the first of their kind in the world and part of the biotechnology revolution that is upon us.
A load of bull you might say? Not at all!
The scientists from US company Advanced Cell Technologies (ACT) who announced these exciting new developments at the IETS Boston conference in January, claim that many more such calves are on their way. They also claim to have used the same technology in pigs, with the first such transgenic, cloned piglets due to be born shortly.
Goats producing human proteins
Transgenic goats producing valuable human proteins in their milk are also part of "what's new".
Genzyme Transgenic Corporation (GTC) has been quietly creating a number of transgenic "founder" goats over the last few years.
At the IETS conference, it was reported that Genzyme now has over 10 different lines of transgenic goats secreting commercial quantities of valuable human proteins in their milk.
Once transgenic founder animals are made (for example one male and one female) they can be multiplied up by traditional methods (such as multiple ovulation and embryo transfer) to produce herds of transgenic animals to be milked for the valuable pharmaceutical proteins that they produce.