Making Life, Better
Welcome to a future in which infectious diseases are not just prevented, but wholly eradicated. Any disease transmitted to humans by insects—gone. Millions of people that would have become infected with malaria, saved. With new gene-editing technology, this future is much closer to becoming reality. Scientists are pursuing a method called gene drive to prevent pathogens from spreading in insects like mosquitoes. Using a gene designed to protect mosquitoes from being infected by the malaria parasite, they plan to engineer mosquitoes that will rapidly spread disease resistance throughout the wild mosquito population. However, changing the genetics of an entire species so quickly could lead to irreversible environmental consequences, not all of them positive. For example, scientists have to consider what would happen if a harmful gene were coupled to the gene drive mechanism, or if the resistance gene mutated or spread to other species, causing universal damage. Malaria and other global problems urgently demand responses, and it is the responsibility of scientists and engineers to design the most effective, safe solution possible. The design and “programming” of new bacteria, fungi, plants, and even animals to solve global problems is what unites the field of synthetic biology. Synthetic biologists seek to understand how living organisms function and apply those underlying principles to create and modify biological systems. The DNA devices and organisms they design, such as the mosquitoes described earlier, have enormous potential and unknown impact across not just medicine, but all fields and disciplines.
Whether it’s engineering mosquitoes or microorganisms, all synthetic biology operates on the same basic premise: synthetic biologists essentially (or literally, for those working on DNA logic gates) code with DNA. Each DNA “program” can be broken up into different abstract parts: the specific genetic instructions that will tell cells what to do or make, a general promoter sequence at the beginning of the program that lets the cells know when to start reading, and a terminator sequence that tells the cell when the instructions stop. Since DNA is the universal basis of life on earth, the same DNA “program” should generalize to wildly different organisms. While this is theoretically true, in practice, cells are so complex that many factors besides just the DNA sequence control how the DNA is expressed (how many times the “program” runs) in different cells. Stanford Bioengineering professor Stanley Qi compares engineering biology to engineering electrical systems: “The logic behind the complex systems from electrical engineering…[can be approximated] using binary language...That’s true for computers…[but] life is more complicated than that. Probably life is not binary…it’s a spectrum.” He gives an example: “Everyone’s different, not because you have a gene [and] I don’t have a gene. Our genes are all very similar, essentially the same—it’s the levels that are different…We more or less like to view life as a transfer curve instead of ‘there’ or ‘not there.’” To account for such differences in gene regulation and transcription of different organisms, synthetic biologists are working on standardizing parts across the board, designing promoters, genes, and terminators that would work the same way in every cell. Standardization projects like BioBricks are helping make synthetic biology easier to use and understand for scientists and students without specific training.
New, accessible tools such as CRISPR/Cas9, which allows scientists to edit DNA cheaply and precisely, are also encouraging further exploration of synthetic biology. Dr. Qi works on Cas9-based technology because he “[regards] it as one of the very powerful potential technologies for the future...it allows us to very precisely engineer any genome we want to modify…and if you can engineer DNA very precisely, everything else may be possible.” Now, technologies that sequence and synthesize DNA, or “read” and “write” DNA code, with the same ease that CRISPR can edit it are needed more than ever. Although DNA sequencing is getting faster and cheaper with new developments, DNA synthesis is still a time-consuming and expensive chemical process. However, as demand grows for DNA synthesis technology to exploit the many applications of synthetic biology, the cost and time needed to write DNA are projected to decrease significantly. Some synthetic biologists are hoping that Human Genome Project: Write, a research effort to synthesize all 3 billion bases of the human genome, will drive down the cost of DNA synthesis as well as enabling huge steps in medicine.
This ambitious project, like most synthetic biology projects, necessitates not only new tools, but also advances in knowledge. Dr. Qi emphasizes that “technology is important and application is important, but another side is equally important, which is the science. We need some people to establish a very solid fundamental, theoretical basis for synthetic biology…but that’s very hard…Basically, you are trying to solve the mysteries behind life.” Since biological systems have so many components that interact in different ways, it’s challenging to predict exactly how an engineered part (whether gene or organ) will behave when inserted into a natural environment, let alone how entire engineered organisms would work. “When we talk about engineering a computer, it’s created by humans…we know where it comes from,” Dr. Qi says, “but when we talk about life, it’s just coming from some mysterious process…We know very little of life, and because of the lack of knowledge of…how it works…it’s really hard to engineer something…You can tweak, you can tinker, but a lot of times you don’t get what you want to get.” Such obstacles have thus far prevented scientists from synthesizing all of the different parts of a cell, but they have managed to construct an entire bacterial genome out of synthetic DNA that can be inserted into a natural cell. Eventually, they hope to learn enough to build a minimal organism, a basic template to be modified by any lab for any specific biological purpose. As the field of synthetic biology continues to develop, it will contribute to a more comprehensive understanding of how life works, from the cellular level to that of an organism.
Synthetic biologists are also dedicated to making their knowledge and tools accessible to all. Many synthetic biology software tools are open-source, and most published papers are freely available online for anyone to read. The development of cheaper sequencing and synthesis technologies, portable gene sequencers and DNA synthesizers, and a wider knowledge base to work from would allow even further collaboration and diversity of ideas in the field. “[Sharing] information…[is] very helpful, especially for an emerging field,” Dr. Qi says, adding that there are “no textbooks” for synthetic biology since “the field goes so quickly and expands into so many other subjects that it’s hard for people to read a book [that came out] years ago and know what people are now doing—so it’s…using the online system to share which is really important.” To get young people interested in synthetic biology and familiarize them with these resources, there’s the iGEM competition, which encourages high school and college students to form teams and create their own synthetic biology projects. Dr. Qi believes that “interest and motivation…and being able to talk with other smart and motivated students across the world…is huge in the long term to encourage younger students.” As those students become professionals, they will be able to apply the design skills and synthetic biology knowledge they have gained to practically any discipline they enter.
Learning how to design effective biological systems, whether from existing organisms or from scratch, could revolutionize not only medicine, but also agriculture, environmental science, and materials science. We could go beyond simple computations in cells to producing less dangerous vaccines, creating bacteria that target cancer cells, and modifying our microbiomes (or even our own cells) to fight off disease and reverse deterioration. For many medical and environmental problems, Dr. Qi reasons, “if you use chemical methods, [they are] very difficult [to solve,] but if you use life, which naturally can produce [results,] but you engineer it in a way to enhance its ability, it’s much better.” Opening mammalian cells, especially human cells, to modification would unlock a new world of possibilities for synthetic biology.
However, synthetic biology initiatives like gene drive would also bring about serious ethical issues that both scientist and society must be equipped to deal with. “From an ethical side, are we allowed to [extinguish] the whole species?” Dr. Qi asks, on the topic of mosquitoes. “Maybe they are doing something that we can’t realize yet. I think that points to a lot of concerns which we should continue to talk about [and pay attention to.]” Some groups are already worried that Human Genome Project: Write would enable the creation of “designer babies” and are troubled by the ethics of artificially creating human life. The potential for misuse of gene-editing tools for bioterrorism, the vulnerability of personal genetic data, and unintended environmental consequences of engineered organisms are problems of increasing concern for the general public, especially as synthetic biology becomes more prevalent. “At the same time,” Dr. Qi amends, “[there is] a lot of excitement about synthetic biology…for manufacturing commodities, and also for therapeutics, so it’s both exciting and concerning. But that’s why the field is so interesting.” Only with a deeper understanding of the science and its effect on society, as well as consistent regulations and policies governing synthetic biology and its products, will we be able to continue advancing such a promising field. Once these provisions are made, all of the benefits to be gained from synthetic biology, whether in the lab, the field, or the clinic, will be just steps away.
Works Cited
Andrianantoandro, Ernesto, et al. "Synthetic biology: new engineering rules for an emerging discipline." Molecular systems biology 2.1 (2006).
James, Anthony A. "Gene drive systems in mosquitoes: rules of the road." Trends in parasitology 21.2 (2005): 64-67.
Ledford, Heidi. "CRISPR, the disruptor." Nature 522.7554 (2015): 20-24.
Pollack, Andrew. "Scientists Announce HGP-Write, Project to Synthesize the Human Genome."
The New York Times. The New York Times, 02 June 2016. Web. 19 Nov. 2016.
Qi, Stanley. Personal interview. 28 November 2016.
