May 5, 2017, (Research Matters):
Imagine if just gulping a glass of milk took care of all your daily protein needs, being that ‘superfood’ dieticians recommend. Or how about a milk-pill - a glass of milk with all the antibiotics you need to ward off that infection? This is not too far in the future, thanks to genetic engineering.
Milk, while being a major source of protein worldwide for growth and survival, is also a commercial food product of significant importance. Over six billion people across the globe consume milk and milk products. An ever-increasing demand for milk has raised an important question - how can this huge demand for milk be effectively met, while still retaining all the goodness of its nutrition value.
Traditionally, dairy farmers have used the technique of ‘selective’ crossbreeding where some breeds of cattle that yield more milk are mated with breeds with other favourable traits like being disease resistant or better suited for local conditions. However, this method sometimes resulted in unwanted consequences.
“When European breeds like the jersey were cross bred with local Indian breeds to increase milk production, some desirable traits of the local breeds were also lost in the process”, explains Dr. Satish Kumar, Chief Scientist and Group Leader at the Centre for Cellular and Molecular Biology, Hyderabad.
Scientists later proposed ‘genetic engineering’ as an alternative to cross breeding. Genetic engineering, as the name says, is the modification of genes - a unit of heredity. Since genes in cows dictate which proteins need to be in milk or how much of these proteins are produced, playing with them allows scientists to obtain some desirable traits. They can increase the protein content in milk, thus increasing its nutritional value, or modify the composition of milk in order to make it more suitable for human digestion or for other therapeutic uses.
Dr. Bruce Whitelaw’s group from the Roslin Institute, Edinburgh in collaboration with Dr. Kumar have recently published a review on the some of the solutions that researchers have developed over the years using tools of genetic engineering. “A key development has been our ability to introduce the necessary genes into the local breeds, without the necessity to cross-breed, which is relatively more uncontrolled”, points out Dr. Kumar about the exciting prospects this field of research has for the future of milk production.
A brief of history of genetically engineered milk
Genetic engineers have been tinkering around with milk for around thirty years. The major effort throughout these years has been to develop animals as ‘bioreactors’ to produce any protein of interest. “It began in 1987”, Prof. Whitlaw recounts, “when mice were made to produce beta-lactoglobulin, a protein that is normally found in sheep milk.”
Using methods like pronuclear injection, the gene responsible for producing the protein of interest was inserted into the fertilized egg (zygote) of another animal. The result was a ‘transgenic’ animal, which after reaching maturity, was able to produce a protein that was not normally present in its milk.
Later, the advent of recombinant technology gave scientists greater freedom in how they could engineer genes. Recombinant technology is a set of techniques where a gene or genes of interest is inserted into an animal cell using a ‘vector’. A vector is typically a circular piece of DNA in which the required gene is inserted at some specific points. The vector then carries this gene into the animal cell. Often, the gene gets integrated into the DNA of the cell, allowing the cell to produce the new protein (as dictated by the new gene). The technology allowed scientists to insert the gene at specific locations in the DNA, as opposed to the random integration done by earlier methods. Hence, genetic engineers could now add genes, remove genes by substitution, and regulate genes by introducing other elements that controlled the amount of the protein produced.
Genes were added not only to increase the protein content, but also to alter the composition of milk for different purposes. For instance, transgenic cattle were engineered to produce milk with elevated levels of β- and κ-casein, proteins that are important for the stability of milk, thus preventing it from spoiling easily. In another study, goats were made to produce human lysozyme, a protein that is known to kill bacteria.
These advances were not only important for producing milk for human consumption; they also held potential for a healthier livestock industry. Pigs were engineered to produce milk with higher lactose levels, which reared piglets that were heavier and grew faster, for example. This strategy has since then been considered to reduce the death of new-born piglets in the pig industry. On the opposite other end, some milk protein genes have also been ‘knocked out’ in mice to study how those particular proteins affected the growth of suckling pups.
The existing techniques have brought breakthroughs and have given us a better understanding of the role of milk proteins. However, they are usually cumbersome and involve several complicated steps, which may not give optimum results. Research in this area never slowed down for this reason, but recently there has been greater excitement about an emerging technology – genome editors.
‘Genome editors’ are the new tools in the kit of today’s genetic engineers that allow precise deletions or insertions at a particular location in the DNA. Using enzymes that act as ‘molecular scissors’, the DNA can be cut at specific locations, inserted, deleted or modified with an engineered genome, and the cuts are later repaired using a required template. The CRISPR/Cas system is one of the three main genome editors that have been developed recently. Because of its high precision and ability to make multiple changes in the same cycle, this system has been quickly adopted by researchers and is set to boost genetic engineering studies. “A particular impetus to write about the status and scope of this field was the CRISPR/Cas system”, recounts Prof. Whitelaw, talking about this technology. “With this system, we can now introduce multiple changes in the DNA precisely where we require.”
Such ‘precision breeding’ using genome editors has already been used to create genome-edited sheep, goats, cattle and pigs.
The future of milk
With the prospect of genetically engineering milk going in every possible way, where are we headed? “The stage is set. We have the technology. It is only a matter of time and we will see many innovations come up”, says Dr. Kumar enthusiastically about the future.
One of them is to ‘humanise’ milk to combat allergy – a common condition among infants and young children – by removing the allergy-causing proteins like beta-lactoglobulin from cow’s milk. Researchers are also trying to develop ‘medicated’ milk by introducing antibodies or vital proteins in cattle milk for the purpose of vaccination and therapeutics. Dr. Kumar gives an example - “Alpha-1 antitrypsin deficiency, which is a serious genetic disorder, can be treated by administering the required protein - alpha-1 antitrypsin - through milk!”
Though the future sounds exciting, there is still a long way to go before genetically engineered milk reaches our table. This might not be merely because of the lack of technology, but also due to other socio-economic and political factors. Irrespective of that, the authors believe that genetic engineering can definitely address the challenge of food security. “This is of significant importance especially in a country like India. Hopefully, the regulatory environment will soon be sorted out, and we can see genetically engineered milk making in-roads in the market as well”, signs off Prof. Kumar.