29 January 2016

Synthetic biology for space programs


Biologist Christopher Carr on manned flights to Mars, the production of medicines in the conditions of a space mission and the effect of radiation on living organisms.

Imagine that during a flight to Mars you suddenly found yourself infected with bacteria that were "hiding" on your spaceship. Unfortunately, you don't have a complete set of all earthly medicines. If you were on Earth, this disease could be easily cured, but you simply don't have the right drug on the expedition. Should we accept and accept that the mission is over, or is there something else we can do? With the right luck and a sufficient level of development of the field, synthetic biology can come to our aid, and we will create the necessary medicine right on Mars. It seems incredible at the moment, but given what we already know, the task looks potentially feasible in the future.

If you don't want to read a relatively long text, you can listen (there's nothing to look at there except the lecturer's head)
An 11-minute video with a good simultaneous translation – VM.


So, with the help of synthetic biology, you can create an organism, for example, the bacterium B. Subtilis. Its genetically modified version is already being used in industry for the production of many enzymes and other products – it's easy to imagine that the body is being modified to produce, say, a simple medicine. Since B. Subtilis is a normal human commensal, it can be assumed that as soon as the medicine is ready, you will be able to drink it immediately. I'm not saying that this is exactly what will happen, but this assumption is not from the realm of fiction. Since B. Subtilis is capable of passing into a spore state, one can imagine a certain card or another collection of various spores of artificially modified organisms. Let's say you need to make a medicine, or synthetic biology can become part of a life support system, or perhaps be used in combination with systems for growing food or other plants, or perform some other function necessary for your Martian mission. Then you could just take this card, choose the right organism, grow it, get the right medicine and get cured of the infection.

Of course, many medicines are too complex for this method of production or have an unsuitable composition. There are many obstacles on our way, but nothing is impossible yet. One of the potential ways to use synthetic biology for space exploration is to use it in unpiloted missions. In the case of a robotic mission, modified organisms can be used as detectors of, say, certain nutrients or compounds at very low concentrations – they will glow green, producing GFP in response to a certain substance, or they could show something else that can be measured. I have listed only a part of the ways to use synthetic biology in future space missions.At the same time, the big problem of synthetic biology today is that we are at the initial stage of the development of this science.

It becomes easier to edit the genome, but we also need ways to analyze living systems; you can create a fluorescent or other gene reporter, but you also want to observe a more fundamental level, to know whether the genetics of such systems is stable. For example, we are creating a tool to search for life on Mars, based on the assumption that if life really exists there, it will be similar to Earth's. So, we are creating a small RNA and DNA sequencer, and if such a sequencer is in the arsenal of people or machines exploring Mars, then it can be used to track the state of a synthetic biological system.

In addition, at a more basic level, before testing such systems in space, it is necessary to show that they will maintain functionality at the level of the entire organism and its components in severe space conditions. Now this is being tested in various empirical ways: B. Subtilis, for example, has been in space and was directly exposed to vacuum in low Earth orbit – there was a wave of publications on this topic in 2013. But we also need to know at the component level whether biological structures can be used in space equipment, whether they can be used as part of synthetic biological systems in future space programs. This is a key aspect of testing our instruments for detecting life on Mars – we use biological components, use DNA polymerase and other DNA enzymes as positive controls, as well as DNA oligomers as primers for sequencing reactions, for PCR.

One of our experiments was as follows: we took a set of such components and subjected them to radiation similar to cosmic radiation. We affected them with neutrons here at the MIT nuclear reactor. More precisely, we did not use the reactor itself, but a california source similar in power to the radiation to which these components would have been exposed during a mission to Mars. Neutrons are not the main element of this radiation, but a very frequent secondary component, and we also used such components of cosmic radiation as protons, which are part of solar and galactic-cosmic radiation. We affected the reagents with protons, this happened with the help of a proton installation at the Massachusetts General Hospital. We also exposed them to heavy iron and oxygen ions at Brookhaven National Laboratory. This is one of the few places, if not the only one, where it is possible to simulate the heavy-ion component of cosmic radiation.

At the moment, at standard relative doses, we detect minor effects. Only at much higher radiation doses, which may be, say, on Europa, some changes were noticeable. We tested the effect of protons only, but the results of their effects were visible, so we can assume that if, for example, you would like to check the presence of life on Europa using instruments with biological components, then you should take care of shielding. Such testing of the functionality of biological components seems to us to be the first steps towards the use of synthetic biology in space. We hope that as the field develops, we will still see its serious application for these purposes.

There are still obstacles that need to be overcome on the way to using the achievements of this discipline. The first and most important thing that comes to mind is radiation, and in second place is the issue of storage. Usually in the laboratory, biological systems are taken care of, they are fed in a timely manner, whether it is C. Elegans or cell culture, we support their existence, protect them, and, accordingly, we will have to do the same in space conditions. This creates an additional burden for the spacecraft on which such a biological system will be located, increases both the cargo of the manned mission and the financing, makes the flight more difficult. These problems need to be solved before using synthetic biology for space programs.

How to do it? One way is to profitably use the developed ability of some organisms to stasis, for example, those that can exist in a spore state or another state with minimal energy consumption, in which they are able to withstand wide temperature ranges and high concentrations of various substances. One example can be slow–moving eukaryotes, which can withstand enormous temperature changes: from almost absolute zero to very high, and one can imagine using the genetic material of these animals to create synthetic or genetically modified systems that can be in a state of stasis for a long time and be woken up on demand.

Thus, synthetic biology is only at the beginning of its development. In a sense, it is a natural step of scientific progress or, perhaps, complements existing knowledge, since it continues the path of genetic engineering, where a lot has already been done. One can imagine many applications of new knowledge within the framework of space programs, but finding out whether they can really be used intelligently will require huge efforts. If we are able to store synthetic biological systems and they can withstand temperature changes, do not require power for a long time, and so on, that is, they will not complicate the mission, then we will be able to use the enormous potential of miniature computers, which we call cells. By reacting to chemical molecules or other signals in the environment, they can help us detect them. Thus, we will replace very complex systems with compact and powerful biological tools.

About the author:
Christopher Carr – Research Scientist, Massachusetts Institute of Technology, Department of Earth, Atmospheric and Planetary Sciences.

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