How did it all start?
Phenotype, genotype, genes, DNA, seem like familiar words from high school biology, right? But how many of us are fully aware of the fact that right from the food we eat to the clothes we wear, use applications of genetic engineering? The world of genetic engineering primarily revolves around a molecule known as the DNA ( Deoxyribonucleic acid). It is found in almost every living cell and carries genetic information that helps an organism to carry out its life processes. It is essentially a blueprint of life. Human beings have been dabbling with it since millennia right from the time they first began to harvest crops and breed animals. Selective breeding over thousands of years allowed us to choose more nutritious crops with desirable traits as well as domesticate wild animals, for example, pet dogs have evolved from domesticated/ friendly wolves who were fed scraps and survived to pass on their genes.
The discovery of the structure of DNA in the 1950's - the famous double helix, allowed biologists to better understand the functioning of DNA. This breakthrough was a foundational block for modern genetics. In 1962, Dr. Norman Borlaug with his team of scientists managed to double the production of wheat, which was earlier plagued by stem rust - a fungus that damaged crop yields and slashed productivity. He did this by cross-breeding his cultivars with a short Japanese variety to make them resistant to disease and falling over. Borlaug's wheat came to the rescue of millions of people suffering from a severe famine in India and Pakistan.
How far we've come
The first genetically modified organism was made by Herbert Boyer and Stanley Cohen in 1973, it was a bacteria resistant to the antibiotic kanamycin. The first genetically modified animal was a mouse, created by Rudolf Jaenisch in 1974. The first GM crop was an antibiotic-resistant tobacco plant produced in 1982. China became the first country to commercialize transgenic plants including virus-resistant tobacco in 1992.In the same year, ‘Flavr Savr tomatoes’ became the first GE food crop approved by the U.S. Department of Agriculture. These tomatoes were engineered to have a longer shelf life by being more resistant to decaying bacteria.
Coming to medicine, until 1982 insulin used to treat diabetics was procured from the pancreas of pigs and cows. But in 1982, Genentech, the first genetic engineering company, brought synthetic human insulin to the markets produced using recombinant DNA technology.
Soon genomics progressed rapidly to produce not just insulin but treating infertility, new vaccinations, growth hormones, cancer drugs, etc. Interestingly, the cheese we so dearly love is made using recombinantly produced cymacin, which is an enzyme that speeds up the coagulation of milk to form curds. This cymacin was traditionally obtained from the stomach linings of goats and cows. The year 1995 saw another striking application of biotechnology in the form of a cotton variety capable of producing its insecticide. Genetic engineering had some fun applications too. In 2001 the 'GloFish’ became the first commercial transgenic animal to flood the markets. This fish was genetically engineered to fluoresce in black light using genes that produce bioluminescence. Salmon that breeds throughout the year shall be in the markets soon. In the food industry, vegetarian chicken, vegetarian burger patties that taste like meat are being produced using synthetic 'Heme proteins' that give blood its color and taste.
In the area of therapeutics, cell gene therapy is being used to edit DNA, to fix a critical defect in the genome. These therapies are being used to treat cancer, leukemia, lymphoma, or genetically inborn diseases like muscular atrophy and blindness. It is really exciting to see how advancements in molecular medicines and gene therapy might eventually help in eliminating diseases like cancer.
The techniques in genetic engineering that we have used so far are Polymerase Chain Reaction or PCR, used to make copies of DNA. Cutting and pasting DNA, mixing one organism's genome with the other, ( Remember Jurassic Park?), that is exactly what we call recombinant DNA or a transgenic organism. We can also insert an edited DNA into a cell, just like a new software on a computer. Presently we can also write DNA sequences using chemical synthesis. This is where we ask ourselves, what will a genetically-engineered future look like?
What lies ahead?
So far we have harnessed and made use of genomes created by nature. Evolution has already gifted us with a treasure of genes. Soon, synthetic biologists want to be able to program and engineer entire genomes by ourselves. Advanced computational techniques have enabled us to better understand biophysical models. Technology is our tool to master biology and understand the design and complex interactions within living cells. An idea that scientists have been working upon is that of personalized cancer vaccines that target the unique tumor in an individual. The ability to engineer genetically encoded molecules like proteins directly might be a game-changer for the treatment of diseases. For example, A universal flu vaccine, that could cover you against the risk of flu not just for that year, but all future years as well.
The two breakthrough techniques in genetic engineering that we have discovered over the last decade are Optogenetics and CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)
Optogenetics involves modifying cells to make them sensitive to light. Take our brain cells for example. Human beings still don't have a complete understanding of how the brain functions. We haven't been able to trace the minute yet significant interactions between groups of neurons that govern brain activity. What if we could switch on and switch off individual cells to assess their impact? That is what we do while researching across every scientific discipline. Isolating variables to study them individually and then assess the collective dynamics. Researchers have already used this technique to control motion circuits in mice. They have also been successful in putting fruit flies to sleep by using a flashlight! Optogenetics could further our understanding of brain physiology immensely.
CRISPR editing is a technique that allows us to not only remove particular genes from a cell's DNA but also add new ones. CRISPR gene editing uses the natural defense mechanism of bacteria and archaea, the Cas proteins such as Cas 9 to protect the bacteria from foreign invaders, ie. viruses. These proteins can recognize and store genetic code and chop off foreign DNA. CRISPR editing could be useful in curing diseases like cancer, cystic fibrosis, cataracts, and muscular dystrophy. One essentially has to remove the mutations and replace them with healthy DNA. If we can edit genomes it also means that you can remove a genetic defect from an embryo as well. It also implies that we can insert genes that produce traits we find desirable, for example, a faster metabolism, stronger muscles, physical features, and even intelligence. Genetic engineering could also help us slow down or even reverse our aging process. Engineered humans may sound like a far fetched dream but is an undeniable possibility in the next hundred years. When we develop techniques precise enough to do the above, everything around us will be inevitably engineered. Right from our external surroundings, to our internal composition. Today we can detect certain defects in an embryo early on and many people do choose to terminate the pregnancy post detection. While that decision might be subjective, indeed, we are already selecting lives that will take birth. While a disease-free and younger world sounds like all you will ever need, genetic engineering could also be used to fight ruthless wars and force unwanted genetic modifications under an authoritarian regime.
The question is who decides what is the right health policy and how far is too far when it comes to genomic editing. The only way to go about it is universal participation and adoption of genetic engineering to facilitate systematic and sensible research and progress. If we argue that gene editing and engineering new genomes are against nature, we forget the fact that human species is itself a creation of nature. Perhaps we evolved this way to advance and explore possibilities to sustain and spread our civilization on and beyond the planet. Nonetheless, genetic engineering is instrumental in building sustainable infrastructure. For example, driveways that could repair themselves, roofs that had bacteria which remove pollutants from the air, superfoods, modified agriculture, bio- machinery and equipment that does not leave a carbon footprint, etc. programming living cells the way we want also gives us the power of creating entire ecosystems on other planets and make them habitable. Self-sufficient space stations and genetically modified astronauts could transform and revolutionize space exploration forever.
For all we know, we will be long gone till these visions turn into reality, but humans have always manifested what they have imagined. Just how aviation and air travel seemed like a fairytale to the medieval generation, we can never really deny that the most obscure idea might lead to an invention a few hundred years down the line.
By :Yeishita Kelkar