animal cloning old macdonalds farm is not what it used to be
(Baronial 2003)
Imagine a typical bulldoze through the countryside. Equally you wait out your window, you notice a farm. At that place are cows and sheep grazing on grass, chickens in the coop and pigs in the sty. However, this is no ordinary farm. What yous don't see is a blood clotting cistron existence produced in the cow's milk, strong however calorie-free-weight spider silk proteins being produced in the sheep, vaccines in the chicken eggs and that the pigs are destined to be a source of transplant organs (xenotransplantation). No, this is no ordinary farm. This farm of the future is actually a "pharm."
Pharming, yet another cleverly misspelled word produced by the biotechnology sector, refers to using transgenic animals (animals that conduct strange genes in their genome) to produce drugs or other products beneficial to humans [1]. While this idea may not exist that new, its implementation is just now beginning to take shape. Numerous companies are springing upward all over the world marketing a plethora of these pharmaceutical products. With our electric current noesis of what affects embryonic development being limited, the major hurdle to the success of these products is the upstanding issues that take arisen through the use of transgenic animals, specially if they are to exist used for human consumption.
A Word About Cloning
Cloning. Mention the word 'cloning' to the average person and often they will tell you the harms of cloning-for instance, how it can be used to generate a population of genetically superior "super-humans." However, frequently the about talked about applications of cloning are those that, in reality, are still fictitious. In reality, fifty-fifty current cloning techniques to creating transgenic animals are very difficult [2]. First and foremost, producing transgenic animals is very costly, ranging in price tags from $20,000 to $300,000. Furthermore, not all transgenic animals produce proteins in large amounts, or they produce them in the wrong tissues. So, if a transgenic animal were produced that expressed the correct protein, in the right tissue, and in big amounts, it would exist benign if its offspring were to exercise the same.
How to Brand Your Own Transgenic Animal
While the technique of cloning has inverse dramatically over the years, the basic principle remains the same [2]. Take a blood clotting factor protein we would like to clone in a cow as an example. Essentially, the cistron for the gene would be linked to a promoter specific for a milk poly peptide. This promoter is responsible for ensuring that the gene is merely expressed in the milk of the animal. Many copies of this promoter-cistron combo are then introduced into a cow'due south egg, which is allowed to develop in a surrogate beast (see Effigy 1). A technique called 'Pronuclear injection' is used to do this and involves injecting the Dna direct into fertilized eggs using a very fine drinking glass needle ( transfection).
However, pronuclear injection is very unreliable. This is due to DNA uptake and integration into the genome of the egg cell being a very rare event, typically resulting in 1 to five transgenic animals out of every 100 being born. Dolly the sheep, the commencement animal cloned by pronuclear injection, was the result of one success out of 277 eggs [3]. Another Biotech visitor, PPL Therapeutics, took several years merely to produce a flock of 600 transgenic sheep.
Information technology was obvious that if pronuclear injection were the only animal cloning technique bachelor, pharming would non be a viable pick. This trouble has been solved by a new technique chosen 'nuclear transfer', which solves the low per centum of transgenic offspring past selecting for eggs that have cloned genes integrated into the egg's genome before information technology is implanted into the surrogate [4] (see Figure 2) Essentially, cells are transfected equally earlier, with the addition of a gene that makes the egg resistant to an antibody if information technology is expressed properly. This allows for the choice of but those cells that properly express the antibody resistance gene, and in conjunction, the gene of interest. The nucleus of these cells are then removed and transferred to an egg that has had its nucleus removed, followed by treating and culturing the egg to allow fusion with the nucleus. Since all the eggs contain the transgene, nigh 100% of the offspring will exist transgenic animals.
Issues with Modernistic Cloning Techniques
While nuclear transfer practically guarantees a litter of transgenic offspring, problems still exist with this method of cloning. Outset of all, non only is integration of the transgene into the genome a very rare upshot, it is likewise random, as scientists have no mode of directing where the transgenes end upward [4]. This ways that the transgene could insert into regions that may exist deleterious to its expression or it may even insert into an endogenous cistron (a gene belonging to the animal) knocking out its function. Secondly, many of the animals are built-in with gross birth defects. These animals tin can be grossly over or nether weight, and many have internal organs that are underdeveloped or deformed. Therefore, even though scientists can produce a full litter of transgenic offspring, there is no guarantee that these animals volition be (a) healthy, (b) express the transgene in big amounts, or (c) express the transgene in the right tissue.
While scientists take greatly improved the techniques used to produce transgenic animals, cloning is still essentially a trial-and-fault procedure. These problems doomed one biotech company, Granada Inc., which tried to make a herd of transgenic cattle. They were forced to shut down, as they could not generate enough calves [iii]. Scientists are however baffled past the loftier charge per unit of birth defects, only they signal out that animals built-in by in vitro fertilization also tend to be born with a high charge per unit of birth defects (albeit at a lower frequency) [3]. This suggests that it is not necessarily the nuclear transfer that is causing the defects, rather how the implanted embryo develops in the surrogate womb. Thus, the search for the ability to target integration of the transgene, and improved methods of culturing and implanting the embryo continues.
Why Pharm?
Outlined higher up are 'the what' and 'the how' of pharming, plus some of the concrete issues associated with information technology. Despite the expense and difficulty in creating a successful transgenic fauna, the benefits can still potentially outweigh the setbacks. For the biotech visitor that is producing transgenic animals, and for its investors, the benefits are obvious — money, and lots of it from pharmaceutical sales. Even so, pharming tin can do good the ordinary person past reducing the cost of pharmaceuticals. Currently, the method of choice for manufacturing many drugs is past laboratory prison cell culture of leaner, yeast, or animal cells [five]. There are many drawbacks to this mode of mass producing drugs: (a) cell cultures crave abiding monitoring and sampling, as cell cultures tend to crave precise parameters in order to produce large amounts of protein, (b) expansion is very plush and laborious, as new equipment is required, as is space to store the equipment, (c) in order to retain biological activity, many proteins require modifications (addition of sugars, for example), some of which are only performed by mammalian cells, and (d) well-nigh cells demand to exist ruptured (non a trivial procedure if you consider the size of modern bioreactors) to isolate and purify the protein of interest, which is much more difficult than purifying proteins from the blood or milk of an animate being. So, even though the initial toll of producing transgenic animals is quite high, using animals equally bioreactors is really a cost efficient alternative to mass produce human pharmaceuticals. I estimate by AviGenics (a individual biotech house, so take these numbers with a grain of common salt) states that while mod cell culture costs roughly $100 per gram of poly peptide produced, pharming the aforementioned protein cost roughly $two to $20 per gram if using caprine animal milk, or $0.10 to $0.25 per gram if using poultry eggs [2]. This volition mean that the consumer volition benefit from receiving pharmaceutical drugs at a fraction of the price.
Some Pharming Projects of Interest
When the Roslin Institute and PPL Therapeutics appear the nascency of Dolly in 1996, quite a stir was created. Dolly, a sheep, was the commencement animal cloned from an adult cell, previously believed to be impossible. A year afterwards, the same group announced the birth of two more cloned sheep, Molly and Polly. Nonetheless, these two sheep were very different from their cousin, Dolly. The virtually pronounced difference was the fact that they both carried the human being gene that codes for a protein called Factor IX [iii]. Gene Ix is a blood clotting poly peptide, and information technology is commonly used to treat patients that accept hemophilia B, a disease that is acquired by a deficiency in Gene 9. The goal of creating Molly and Polly was to produce a herd of sheep that produced Cistron IX in their milk. The only other source of Factor IX is from man claret plasma. Past producing Gene IX in sheep milk, it is hoped that the cost of product will be profoundly reduced.
Avant-garde Cell Technology, Inc is using the queen of milk product, the moo-cow, for potential use as bioreactors [4]. They have produced transgenic cows that secrete the poly peptide serum albumin in their milk, a protein that is used to extend blood volume and is used in patients suffering from traumatic injuries, such equally burns. Cows are an obvious choice for pharming purposes as they can produce up of 8000 Fifty of milk per year, and an estimated xl to fourscore kg of poly peptide a year [4]. That is quite a substantial corporeality compared to the 4 kg of protein per twelvemonth in goats and 2.v kg of protein per year in sheep [4].
One interesting project is that taken up by Nexia Biotechnologies. For years humans have wanted to utilise the silk of spider webs for many applications, as the silk is strong, elastic, and extremely lightweight. However, unlike silk worms, spiders cannot be farmed for their silk, as spiders are extremely territorial, plus information technology is not the consummate web that is desired, rather a portion of the web referred to as frame silk [4]. Cell cultures accept been unsuccessful for producing spider silk, as they tend to produce fibres that are too curt for commercial applications. Nexia Biotechnologies has been successful at producing spider silk in the milk of goats, and is in the procedure of developing "Biosteel®", a man made textile made of spider silk [6]. Potential applications of this cloth are extensive, ranging from medical uses (wound closures, dressing, patches, glues, prosthetic devices), to armed services uses (strong, calorie-free-weight body armour), to sporting appurtenances (biodegradable line-fishing line).
Ethical Issues to Pharming
Many of the ethical issues that arise from pharming surround the handling of animals [vii]. Fifty-fifty with the 100% transgenic offspring produced by nuclear fusion, many are built-in with nascency defects and gross abnormalities or exercise not produce the protein of interest. Additionally, while 100% of the animals born are transgenic, a large number of eggs are used in the procedure of finding one tin can be implanted. This in itself may non be too alarming, all the same, most of the fourth dimension the egg "donor" is slaughtered in the donation process.
Another issue is the idea of the age of the clones [8]. Dolly recently passed away at the age of half-dozen and a one-half. Considering that the average sheep lives for 11 to 12 years, this was quite young. Dolly died from a lung disease found but in old sheep, adding to speculation that cloning animals may consequence their historic period. In fact, many cloned animals tend to die young, some inside weeks of birth. When the Roslin Constitute and PPL Therapeutics appear the birth of Molly and Polly, they had a litter of six lambs out of xiv cloned embryos. One died within hours of birth, and three more died presently later on, leaving the globe with Molly and Polly.
Finally, as transgenic animals are being produced, biotech companies are quick to patent their work in order to maximize their profits. This raises the issue of animal rights, and whether or non these animals volition be treated as sentient beings or whether they will merely be treated as walking factories.
Conclusion
Pharming promises a earth of cheap pharmaceutical drugs, new medical applications, and even the possibility of wearing your new spider silk jacket to the hippest bar in town. All the same many of the products can even so exist produced alternatively (i.due east. cell civilisation) and while pharming promises to produce the aforementioned pharmaceuticals cheaper and better, that realism is too far abroad to determine whether or not it can exist delivered. Moreover, the ethical bug surrounding the use of animals equally pharmaceutical factories is however beingness debated, let alone new debates every bit new awarding of pharming are suggested. Pharming'due south promise is heady and the existent farm is sure to new be the aforementioned.
Additional Reading
i. Clarke A.R., ed. (2002). Transgenesis Techniques: Principles and Protocols. Totowa, NJ: Humana Printing. 351p.
2. Baldi P. (2001). The Shattered Cocky: The Terminate of Natural Evolution. Cambridge, Mass: MIT Printing. 245p.
iii. Yount L. 2000. Biotechnology and Genetic Engineering. New York: Facts on File. 280p.
4. Rifkin J. 1998. The Biotech Century: Harnessing the Factor and Remaking the Earth. New York: Jeremy P. Tarcher/Putnam. 271p.
References
i. Rosenfeld A. (1998). New breeds down on the pharm: plain old barnyard animals — with genes from other species added — are producing medicines that proceed people alive. Smithsonian 29(4): 22-30.
2. Rittner M., Cummings D. (1999). Animal Pharming: The Industrialization of Transgenic Animals. Centers for Epidemiology and Brute Health:
three. Pennisi E. (1998). Later on Dolly, a Pharming frenzy. Science 279: 646-648.
4. Dove A. (2000). Milking the genome for profit. Nature Biotechnology 18: 1045-1048.
viii. Sgaramella V., Zinder N.D. (1998). Dolly Confirmation. Science 279: 635.
(Art past Jane Wang – notation that high res versions of image files bachelor hither)
Source: https://www.scq.ubc.ca/the-new-macdonald-pharm/
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