Laboratory equipment in the MICALIS quantitative metagenomics (MetaQuant) experimental facility. © INRA, INRA

How synthetic biology could benefit from the social sciences

Defining synthetic biology: the first challenge

Synthetic biology aims to generate new organisms and biological functions that cannot be found in nature; its goal is to amass scientific knowledge and develop practical applications. Its proponents say it is an emerging field of biology whose methodological approaches draw upon the biological sciences and bioengineering.  

By Pascale Mollier, translated by Jessica Pearce
Updated on 01/25/2016
Published on 10/10/2014

Automated high-throughput pipetting system used by the MICALIS quantitative metagenomics (MetaQuant) experimental facility. © INRA, Bertrand NICOLAS
Automated high-throughput pipetting system used by the MICALIS quantitative metagenomics (MetaQuant) experimental facility © INRA, Bertrand NICOLAS

A field that is hard to define

According to one common definition, synthetic biology is a field of study that aims to design and build new biological systems with predictable and reliable functions that can be used to advance fundamental research and develop practical applications. Goals can range from constructing simple molecules (e.g., enzymes) to building cell machinery (e.g., membrane pumps or signaling systems) to creating whole organisms (e.g., microorganisms designed to produce useful compounds such as biofuels or medicines). In Canada, synthetic biology is often referred to as biological engineering. However, no single definition exists. As one MIT researcher has said in jest, “If you lock six biologists in a room together, they will come up with seven different definitions for synthetic biology.”

Is synthetic biology a science or a technology? Is it truly a novel discipline or simply a subfield of molecular genetics? These questions continue to fuel debates among biologists and between biologists and engineers.

A limited number of applications developed thus far

So far, synthetic biology has produced only a couple of fully developed applications. One of these is the production of artemisinin, an antimalarial drug. This compound, which is naturally present in sweet wormwood (Artemisia annua), a medicinal herb, can now be produced in large quantities by a genetically engineered strain of baker’s yeast: in a feat of technological prowess, the 12 genes that the plant needs to synthesize the compound were transferred into the yeast. Another application is the production of a synthetic form of hydrocortisone using alcohol and sugar.

However, many studies are currently being carried out, and the applications envisioned by synthetic biology’s supporters have enormous potential. These applications include using diagnostic tools based on modified nucleic acids to clinically follow patients infected with AIDS or hepatitis; exploiting spider silk in the aviation and automotive industries; employing bacteria or microscopic algae to manufacture alternative biofuels (e.g., butanol, isobutylene, or bio-oils); and engineering oil-degrading bacteria to clean up oil spills (1).  

Improving our understanding of life’s complexity

If we could program a living cell as easily as we program a circuit board, we could get the cell to produce desired proteins on demand. However, this possibility still remains far in the future, even if our understanding of—and ability to model—living systems has progressed enormously since the first decade of the 21st century thanks to increasingly sophisticated informatics tools. The challenge is understanding the basic rules that govern a cell’s interactions with its environment. Understanding and modeling these interactions are the goals of integrative biology and systems biology, respectively.

In contrast, synthetic biology places a much greater emphasis on modeling with a view to building new biological systems; it uses two main approaches. The first, the “bottom-up” approach, involves assembling BioBricks (2) into genetic circuits that have been modeled beforehand using computers. These circuits are then inserted into host organisms capable of functionally translating them. The second approach, called the “top-down” approach, involves modifying existing organisms by adding or removing genes (3).

However, once again, it is more than simply a matter of connecting different components, as you would to build an electrical circuit. The process is much more complex because of the multiple interactions that take place among the parts that make up living cells.
 
(1) Certain bacteria naturally have this ability, as was seen in promising research carried out in 2010 in the Gulf of Mexico.

(2) BioBricks are characterized DNA sequences that are listed in the open-access Registry of Standard Biological Parts; the registry contains information on BioBrick function and performance. The scientists who came up with BioBricks compare them to Legos, in that they can serve as the building blocks for a variety of complex structures.

(3) There are also two other, more futuristic approaches. (1) Inserting artificial genomes into “protocells,” cells that are themselves artificial. Protocells are nanobiosystems that currently cannot self-replicate. (2) Building living systems from novel genetic codes.  

Genetic engineering has a relatively long history…

  • 1912: Stéphane Leduc, a medical doctor, maintains that synthesis must follow analysis when seeking to validate scientific results. This idea was later expressed in different terms by the renowned physicist Richard Feynman (1918-1988), who said: “What I cannot create, I do not understand.”
  • 1965: Robert Burns Woodward receives the Nobel Prize for having synthesized a number of organic compounds, including quinine, cholesterol, cortisone, and chlorophyll.
  • 1970: Har Gobind Khorana, a biologist from India, synthesizes DNA from transfer RNA.
  • 1984: Steven Benner’s laboratory synthesizes a gene that codes for a protein.
  • 2002: Eckard Wimmer’s research group at State University of New York, Stonybrook, reconstructs the poliovirus genome (7,741 base pairs) “from scratch”, that is to say without the help of a natural template. Instead, they use the published RNA genome sequence.
  • 2004: First international meeting on synthetic biology is held at MIT (Cambridge, Masschusetts).
  • 2005: Synthesis of the genome of the viral strain that caused the Spanish flu (Tumpey et al., Science, vol. 310)
  • 2010: Craig Venter’s research group synthesizes a bacterial genome (1.08 million base pairs long) and gets it to function in another bacterial species. Venter dramatically announces to the media that his group has recreated life and thus evokes both fascination and fear. This interpretation of the significance of this feat is contested by other scientists, who feel that Venter and colleagues did no more than insert a copy of existing DNA sequences into a naturally occurring bacterium.

A fork in the road or progress along the same path?

“Synthetic biology was born from a meeting of molecular biology, informatics, and the engineering sciences. Neither the engineers, who only recently have become interested in looking more closely at DNA, nor the biologists, who ignored the potential of engineering approaches in their quest to acquire more knowledge, could fully anticipate the technological shakeup that would result from this meeting. […] The information available in public databases and the DNA sequences of hundreds of organisms are now serving as a source of inspiration for a type of biology that is synthetic, that is producing genomes freely inspired by those present in nature. Tomorrow, it may move on to creating them from scratch, without using any natural templates. In retrospect, this progression seems logical, but it does not stem from any conscious effort on the part of the scientific community nor a readily accessible scientific “roadmap.” [These advances] are forcing society to ask itself questions about the nature of rapid technological progress and the approach that should be adopted in situations in which scientific research starts pulling society in unanticipated directions or, more importantly, into uncharted territory.”

Extract from the January 2014 Opinion (on synthetic biology) published by the Common Advisory Committee for Ethics in Agricultural Research