From the scientific point of view, Dolly opens many new doors. But as far as Novo Nordisk is concerned it is not particularly relevant right now.

Research partners PPL Therapeutics’ quantum leaps in cloning technology are of no immediate significance for Novo Nordisk

The cloning breakthrough will have no immediate effect on Novo Nordisk’s collaboration with PPL Therapeutics on transgenic sheep that produce vital medicine in their milk. They have had a human gene introduced into their cells, with the result that they produce an extra protein in their milk. When separated from the milk and purified, this protein becomes a vitally important drug, coagulation Factor VIIa, for example, of life-or-death importance to haemophiliacs.
Novo Nordisk researcher and project manager, Jan Lund Ottesen, who has a PhD in transgenic animals, says, "The important prospect as far as we are concerned is that at some time or other, we may be able to clone a transgenic sheep with a high concentration of medicine in its milk and thereby acquire a completely identical group of animals which can all be expected to have high concentrations of medicine in their milk. Because it is faster and more controllable, such a method of breeding medicine-producing sheep can be of commercial advantage and make it easier to gain authority approval.
"Having said that, I must emphasise that before somatic cloning is used, all risks must be thoroughly analysed. We must also be quite certain that the animals do not suffer in any way by being created by cloning."
Ottesen and his research colleague in Novo Nordisk, Christian Grøndahl, point out that it has already been possible for ten years to breed identical animals with the same genes by so-called embryonic cloning - separation of cells in a fertilised egg.
"But if somatic cloning is more refined over the next 10 or 20 years, transgenic animals will allow us to be on the market faster - and cheaper - with new preparations produced in ‘cloned factories’, genetically identical sheep with extraordinarily high production of proteins that can be used to treat serious illnesses in humans," says Grøndahl.

Application potential
The two researchers regard somatic cloning primarily as a stepping stone that will allow basic research to move on.
"We see new possibilities for progress in a number of diseases which researchers have still not managed to come to grips with. Certain forms of cancer, in particular, but also other serious diseases, such as diabetes and Alzheimer’s."
Ottesen and Grøndahl explain that further research into cloning will reveal new facts about those mechanisms that make it possible to re-program cells.
"We know from work on transgenic mice that it is possible to ‘switch off’ certain genes and thus study various treatment techniques and strategies. With the cloning of somatic cells in their arsenal, researchers may one day be able to produce an "Alzheimer’s pig" that will expand our understanding of the disease and perhaps enable us to discover why it occurs in some people and not in others."
The two researchers also see some obvious implications for organ transplants from animals to humans. The cloning technique, combined with the ability to produce pigs whose tissue-typing antigens are ‘switched off’, could provide the key to rejection, allowing kidneys, hearts and corneas from pigs to be transplanted into humans.

Strategic investment
Today, Novo Nordisk holds approximately 9% of the shares in PPL Therapeutics. The alliance was started at the beginning of 1995 and represents a strategic research-driven investment.
Ulrik Spork, responsible for corporate development projects in Novo Nordisk: "Dialogue with PPL was opened in 1994 by ZymoGenetics, our American research centre. What we were interested in was gaining access to PPL’s technology in the production of proteins in transgenic animals.
"For a while, Dollymania was the cause of a huge rise in the price of the shares. But they have since fallen to the 1996 flotation price level. Such a rise, of course, could be of great value to Novo Nordisk if we decided to sell, but we are first and foremost interested in a long-term strategic alliance."
Spork does not regard Dolly as of particular commercial interest. "From the scientific point of view, Dolly opens many new doors. But as far as Novo Nordisk is concerned it is not particularly relevant right now. PPL’s primary role, as far as we are concerned, is to produce four-legged factories in the shape of transgenic sheep, whose enormously productive milk glands make it possible to produce proteins which would be impossible, or at least extremely difficult, to produce in any other way. So access to this technology could well be decisive in determining whether a preparation can be brought to market or not."
Apart from Factor VIIa, which today is produced with the help of fermentation technology and has been marketed by Novo Nordisk since February 1996 under the name of NovoSeven®, Spork mentions therapeutic proteins such as protein C and fibrinogen, which Novo Nordisk and PPL are working on jointly to develop in transgenic animals but have already decided to not produce themselves.
"Our collaboration with PPL in the widest sense is based on the ability to draw on their expertise and capacity when we need to evaluate the potential of new therapeutic proteins to be produced by transgenic animals. PPL is also our production partner when we find it relevant to use transgenic animals," says Spork.