The bold dream of synthetic biology is a world in which all living things can be reliably engineered in ways that help everyone and everything. In this dream, we can use genetics to program living organisms: “if condition A is met, then do action B.” To give a near-term example, bacteria might produce a medicinal protein only in the presence of indicators of a particular disease. Why use living systems and not a vat of chemicals? Because natural systems routinely perform complex chemistry that scientists can only envy, and they do it at room or body temperature, without the need for toxic chemicals or outside aid. Better still, living factories are far more energy-efficient than anything made of silicon and metal. Biology is fast, clean and green. And we should use such systems because people and ecosystems are alive, and the best way to repair life is with life. To fight an evolving pathogen, use an evolving cure. There are problems, though, in bending nature to our own ends. Adopting an organism to work for us means it is using energy that could otherwise be spent replicating, so it will not reproduce as well as competitors. Evolution will constantly select for faster-reproducing mutants that no longer do what we want. Biology’s greatest strength is its capacity to replicate and evolve, but that also presents the greatest challenge. One way around this is to incorporate limits on the ability to change, particularly for those few cases where our changes might be able to spread in the wild. For example, one approach is to employ unnatural amino acid tethers: they make essential proteins within cells wholly dependent on chemicals that do not exist in nature. If the amino acids are withheld, the proteins will not function, and the bacteria cannot grow out of control. We are also better at building within the scope of evolutionary limits: microbes are now programmed to release a burst of complex molecules and then die, mostly avoiding evolutionary selection against production. Cellular pathways can be reworked to eliminate most unwanted side effects. Engineered viruses that target bacteria will kill invading pathogens, multiply until the invaders are gone and then stop, leaving the patient untouched. We must also be careful to make sure benefits always outweigh the risks of reworking organisms. Mistakes are inevitable. Thus, the projects have to be worth it, especially the earliest examples that must justify the technology to the world. Bacteria can be built to make a slightly cheaper flavor of vanilla, but is that a significant boon to humanity or the environment? This is likely not enough to be a pioneering example of a novel technology or to justify its use. On the other hand, building cells that can selectively destroy cancer or cure diabetes is something everyone can get behind. The greatest biological risk to civilization stems from pandemics of infectious disease. Until now, these were inevitable, but we might soon use biotechnology to stop them. Ordinarily, a person’s body confronts an invading pandemic pathogen by evolving its own defenses, creating a whole series of antibodies in the hope that one will effectively neutralize the invader. It is a process of trial and error that takes time; this is why you are typically sick for three to four days before getting well. Sometimes that is just too long, and people die. A better strategy is to give the human body a head start: Take the genes for several known protective antibodies, put them into the harmless shell of a virus and inject that virus into people. The virus enters their cells, which then start to churn out already optimized protective antibodies against the invader, ending the threat. Finally, as scientists we need to respect the fact that engineering life unsettles many people. That means we must consider social risks as well as technical ones. We cannot just explain what we are doing—that only convinces other scientists. Instead we must relate why we care, who could benefit and what the risks may be. Above all else, we should actively invite concerns and criticism from the earliest stages because no matter how great our expertise, we cannot reliably anticipate every consequence on our own. At its best, science is a fundamentally shared undertaking. If we are to engineer life, let us all decide how to do it together.
Why use living systems and not a vat of chemicals? Because natural systems routinely perform complex chemistry that scientists can only envy, and they do it at room or body temperature, without the need for toxic chemicals or outside aid. Better still, living factories are far more energy-efficient than anything made of silicon and metal. Biology is fast, clean and green. And we should use such systems because people and ecosystems are alive, and the best way to repair life is with life. To fight an evolving pathogen, use an evolving cure.
There are problems, though, in bending nature to our own ends. Adopting an organism to work for us means it is using energy that could otherwise be spent replicating, so it will not reproduce as well as competitors. Evolution will constantly select for faster-reproducing mutants that no longer do what we want. Biology’s greatest strength is its capacity to replicate and evolve, but that also presents the greatest challenge.
One way around this is to incorporate limits on the ability to change, particularly for those few cases where our changes might be able to spread in the wild. For example, one approach is to employ unnatural amino acid tethers: they make essential proteins within cells wholly dependent on chemicals that do not exist in nature. If the amino acids are withheld, the proteins will not function, and the bacteria cannot grow out of control.
We are also better at building within the scope of evolutionary limits: microbes are now programmed to release a burst of complex molecules and then die, mostly avoiding evolutionary selection against production. Cellular pathways can be reworked to eliminate most unwanted side effects. Engineered viruses that target bacteria will kill invading pathogens, multiply until the invaders are gone and then stop, leaving the patient untouched.
We must also be careful to make sure benefits always outweigh the risks of reworking organisms. Mistakes are inevitable. Thus, the projects have to be worth it, especially the earliest examples that must justify the technology to the world. Bacteria can be built to make a slightly cheaper flavor of vanilla, but is that a significant boon to humanity or the environment? This is likely not enough to be a pioneering example of a novel technology or to justify its use. On the other hand, building cells that can selectively destroy cancer or cure diabetes is something everyone can get behind.
The greatest biological risk to civilization stems from pandemics of infectious disease. Until now, these were inevitable, but we might soon use biotechnology to stop them. Ordinarily, a person’s body confronts an invading pandemic pathogen by evolving its own defenses, creating a whole series of antibodies in the hope that one will effectively neutralize the invader. It is a process of trial and error that takes time; this is why you are typically sick for three to four days before getting well. Sometimes that is just too long, and people die. A better strategy is to give the human body a head start: Take the genes for several known protective antibodies, put them into the harmless shell of a virus and inject that virus into people. The virus enters their cells, which then start to churn out already optimized protective antibodies against the invader, ending the threat.
Finally, as scientists we need to respect the fact that engineering life unsettles many people. That means we must consider social risks as well as technical ones. We cannot just explain what we are doing—that only convinces other scientists. Instead we must relate why we care, who could benefit and what the risks may be. Above all else, we should actively invite concerns and criticism from the earliest stages because no matter how great our expertise, we cannot reliably anticipate every consequence on our own. At its best, science is a fundamentally shared undertaking. If we are to engineer life, let us all decide how to do it together.
