Synthetic Biology’s Origin Story
The franken-cells of today’s labs have a 10,000 year history.
As long as humans have farmed crops and domesticated animals, they have practiced genetic engineering. By selectively breeding animals and plants with the most favorable traits, early agrarians were able to breed genetically engineered species specific to their needs. Genetic engineering mimics the process of natural selection, but selective breeding speeds up this process and selects traits most advantageous to humans.
The modern conception of genetic engineering — white-coated figures in a lab manipulating gene sequences to create modern Franken-creatures — has its origins in the latter half of the twentieth century. Rapid advances that allowed scientists to manipulate genetics came swiftly after James Watson and Francis Crick’s 1953 discovery of the double helix structure of DNA.
The following discoveries have accumulated into a toolbox, a dynamic collection of methods to manipulate genes. One of the first tools added came in the 1960’s with the discovery of endonucleases, enzymes which cut DNA at specific sites. These enzymes allowed scientists to break into the genetic code, opening the possibility for additions and deletions manufactured by humans.
The next vital addition to the toolbox was a 1973 experiment performed by Herbert Boyer, Paul Berg, and Stanley Cohen, which marked the first instance of recombinant DNA cloning. Their lab introduced genetic material from one organism into the DNA of another organism, where it was successfully replicated. In the early 1980s the first transgenic mouse was created and added yet another vital tool to the geneticist’s toolbox. This was accomplished by taking a mouse embryo and inserting genes into their genetic code early in embryonic development. Through this method, mice can now be given genes that lead to cancer or those that cause them to express a green fluorescent protein and glow under blue light!
The tools accumulated by genetic engineering led to the birth of synthetic biology. Rather than implanting the genes of one organism into another, synthetic biology works on a much smaller scale with more customizable genetic components. Synthetic biologists piece together genetic codes for individual proteins or functions, thus writing a totally new sequence that can carry out a process found nowhere in nature.
Synthetic biology came into its own in the 1990s with the use of systems microbiology which allowed for a complete sequencing of microbial DNA, measuring levels of cellular contents and DNA outputs, and working towards a more comprehensive understanding of cellular networks.
The first half of the 2000s were the foundational years of synthetic biology; using what would become the standard cell used for synthetic biology, E, coli, scientists mapped out gene regulatory circuits. These circuits show the flow of genetic instructions and outcomes, and are similar to electric circuits. The second half of the 2000s saw expansion in the field of synthetic biology and important breakthroughs including “AND” logic gates. The concept of logic gates comes from the circuit building in electronics, that translate an input into an output. This output can be one of two conditions (a 0 or 1 in binary terms). Specifically, an “AND” logic gate needs two input signals to be present to produce an output.
The first half of the 2010s has seen synthetic biology grow in leaps and bounds in and out of the lab. One of the most exciting discoveries was a circuit generated in 2009 able to remember events. These counter circuits rearranged DNA within the same genomic strand to create a permanently encoded “memory”.
In 2013 a major milestone showed synthetic biology’s practical application when the drug company Amyris used yeast to produce a cheaper version of a popular malaria drug (the very same Amyris discussed in last week’s post for its deal with Michelin to synthetically derive rubber for their tires). According to Peter DeNardo, the Director of Investor Relations and Corporate Communications for Amyris, the company was first “approached by the Bill and Melinda Gates Foundation to try to come up with a synthetic version of Artemisinin which, according to WHO [The World Health Organization], is a good combination therapy for malaria.” Traditionally, however, artemisinin was sourced from the plant Artemisia annua a Chinese variety of wormwood traditionally used in natural medicine. however, as DeNardo explains “The problem with that plant is that it was very rare, hard to source, supply security problems, and very expensive.” Therefore, a new manufacturing method would allow a cheaper drug to be produced, thus widening its availability. Using yeast, another popular organism for inserting novel sequences, Amyris engineered a pathway to have yeast pump out the antimalarial drug, artemisinin, allowing for much cheaper production of the life saving drug. As DeNardo explains: “For thousands of years people have used yeast and sugar to make alcohol. Yeast is a very powerful source of DNA and there are many ways in which you can alter the insides of the yeast so that after you feed it sugar, instead of spitting alcohol out its rear end, you can determine something else for it to produce instead. We are exploring numerous ways of leveraging what we call a ‘living factory’ to produce chemicals and molecules that are of commercial interest.”
The practical outcomes from synthetic biology and genetic implantation have been a whirlwind of exciting discoveries. These discoveries range from the cheaper and more efficient production of medications to the strange creation of goats that produce spider silk in their milk, industrial chemicals derived from food waste, and harnessing the power of pigeon poop for good.
These goats, developed at the University of Wyoming in 2010, have had the silk gene implanted into their genetic code in such a way that they produce spider silk protein in their milk. While certainly an unexpected strategy, this solution is actually a perfect marriage between genetic engineering and nanotechnology, another burgeoning field. The spider silk harvested from the goat milk can be used to make things such as artificial ligaments and tendons and bulletproof materials.
Modular Genetics, a Massachusetts based biotechnology engineering company, has developed a way to produce surfactants from waste produced by the food industry. Surfactants are a vital chemical component in many industrial products because of their unique ability to create a stable mixture of water and oil. The production of surfactants creates enormous amounts of waste, and some production methods even create toxic byproducts. To solve this problem, Modular Genetics has created a bacterial organism which can synthesize surfactants from cellulose rich sugar. Humans do not have the enzymes to properly break down cellulose, and thus this byproduct of the food industry can now be used to produce necessary chemicals in a way that is far less damaging to the environment than current methods.
Another innovative practical application isthe concept of Pigeon d’Or (French for Golden Pigeon). This project proposes using the widespread presence of pigeon droppings as a chance for urban sanitation. Using bacteria similar to those found in yogurt, it allows the pigeons to poop out what is essentially detergent. The team that proposed this innovation postulated that the cleaning poop could aid in removing pollution from major cities and also eliminate disease at its source. Though this project is yet to be implemented, it is just one of many examples of the thrilling and sometimes strange developments from synthetic biology.
