Feb 01 2019

Drug-Laying Chickens

One of the ways in which medicine advances is developing better, faster, cheaper ways of mass-producing needed pharmaceuticals. Chemists working for pharmaceutical companies are always looking for a better pathway to get to their desired product. Protein-based drugs are particularly difficult and expensive to manufacture – proteins are large molecules of precisely sequenced amino acids that also have to be folded into a particular configuration. The best way to produce proteins is within living cells.

Initially protein drugs were simply harvested from plants or animals. Insulin, for example, was originally sourced from cow (bovine) or pig (porcine) pancreas. This was an expensive process, and the resulting insulin was not pure, and also was not human. This resulted in decreased effectiveness, some variation in purity, and the tendency to produce immune reactions.

In 1978 the first recombinant human insulin was produced using E. coli bacteria in which the gene for human insulin was inserted. Recombinant human insulin came on the market in 1982, increasing the availability, safety, and effectiveness of insulin and reducing the cost.

This that time this technique has been used to make a host of medical and non-medical protein products, using bacteria or yeast. Most cheese, for example, is used using rennet derived from genetically modified yeast. Prior to that rennet was harvested from the stomach lining of calves. The modern cheese industry would essentially not exist without GM rennet.

Other types of organisms can also be used to make human proteins for drugs or proteins for industry. This brings us to the science news referenced in the headlines – researchers have genetically modified chickens to lay eggs that have a human protein in the white part of the egg. These chickens or their eggs will never enter the food chain – their purpose is solely to produce protein-based pharmaceuticals. So far they have created chickens whose eggs contain Macrophage-CSF or Interferon Alfa-2A. The former is being developed to stimulate tissue healing, and the latter is an immune-modifying protein with anti-viral and anti-cancer effects.

These chickens were modified using a viral vector (using a lentivirus). However, CRISPR can be used to more quickly, cheaply, and precisely make modifications in the future.

The potential advantage here is that you only need to make one rooster with the desired genetic modification and then you can scale up production as much as you want simply by having them reproduce. Hens lay about 300 eggs per year, each containing a nice packet of desired protein. They argue this will further reduce the cost of producing protein-based drugs, with lower infrastructure costs and easy scalability. Add in CRISPR and the costs come down further.

The regulatory hurdles are still significant, however, and bringing any resulting protein drug to the market will take years. However, the hurdles for veterinary medicine are much lower and so they could be used in animals much more quickly, while human versions are being developed.

This type of technology is one of the promises of CRISPR. There is also no reason why we can’t modify plants to produce some proteins, and then we can literally grow drugs. Plant-based protein production may be even cheaper than egg-based, and won’t have the ethical objections that some may have using animals in this way. You also would not necessarily need to use crop or even edible plants, so there is no chance of getting into the food supply. The plants just need to make the desired protein, which can be purified from the ground up leaves or whatever. Other precautions can be taken so the drug-producing plants don’t get out into the wild.

This is just one way in which we are entering the age of genetic manipulation. This is already a critical technology for modern medicine, and will likely become far more so over this century. The potential benefits are too great to ignore. There has been a lot of fearmongering among the public of the dangers of genetic manipulation, as if it is “unnatural” in some vague sense. Rather, we should respect the power of this technology, both good and bad.

There is no reason why we cannot reap the benefits of genetic technology, but in a carefully regulated way so as to minimize risk. We do this with many technologies, and genetic modification is no different. There are real risks, and they should not be minimized, but neither should they be overblown to scare the public away from a potentially life-saving technology. Ask any diabetic dependent on insulin how they feel about the risks vs benefits of recombinant medicine.


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