On Discovering Life

Global Reset / by Dimitar Sasselov /

Two separate quests, one to discover habitable worlds, the other to synthesize artificial organisms, now unite to redefine “life” and its place in the universe.

CERN’s Large Hadron Collider has begun refining our understanding of the fabric of space and time, and NASA’s Kepler mission is sharpening our estimates of how common Earth-like planets are in our galaxy. Yet as these cosmic-scale projects open the second decade of the new millennium they are returning science to a frontier that seems oddly 19th century. Science is going back to the scale of life—that middle ground of minute energies and high complexities that lies between the immense galaxies and the infinitesimal particles.

My statement that life is science’s new focus sounds naive and out-of-touch—after all, just open the newspapers or see the research budgets for biology and medicine, and you’ll notice an overwhelming amount of interest and funding for the life sciences. But that all has to do with us humans: first and foremost, with our health and bodies, and second, with our environment, the ecosystems of planet Earth. There is an aspect of life sciences that has been largely absent: the confrontation of fundamental questions of biology much as particle accelerators grapple with fundamental questions of physics. The roll call of early pioneers and prospectors is notable, but short. Fortunately, increasing numbers of researchers are now re-entering this fertile frontier.

The open secret of this emerging frontier is that we do not have a fundamental definition or understanding of life. Similarly, we do not understand life’s origins, how life emerges from chemistry. We do know that the chemistry of life on Earth, or “Terran” biochemistry for short, is rather restrictive in its molecular permutations. Unnecessarily so, it seems, given the enormous choice of good options provided by chemistry for building biological bodies and functions. However, we do not know whether nature or nurture is the reason. The bio-chemistry we see (and are!) could be universal, like gravity, where the same basic rules apply anywhere. Or our biochemistry could instead be one of many options, one that just happened to fit Earth’s environmental conditions.

The question of alternative biochemistries, learning whether they are possible or not, now appears tractable, and though this does not directly answer the big questions of life’s definition and origins, it represents a giant leap in the right direction. Of course, looking blindly for possible pathways to Terran or to alternative biochemistries would be a depressingly pointless endeavor, given the seemingly infinite possibilities. But if we assume that the emergence of life in general is a planetary phenomenon, then the possible geochemical environments within and outside our solar system are constrained by planetary science and astrophysics. These disciplines allow us to estimate both the initial conditions on early Earth for the pathway to Terran biochemistry, as well as conditions in other planetary systems for any alternative biochemistries.

Two simultaneous but distinct approaches have defined the work on the origins and biochemical diversity of life. One approach is from within, following paths that begin with existing Terran biochemistry and move away from its set of molecules and networks in search for alternatives. The other approach is from outside, following paths from plausible prebiotic initial conditions. Both approaches have scored recent breakthroughs. John Sutherland’s lab (University of Manchester), in a brilliant example of systems chemistry, has performed a synthesis of nucleotides—building blocks of genetic molecules like DNA and RNA—in which two of a nucleotide’s crucial parts, the base and the sugar, emerge as a single unit under natural conditions. Moving in the opposite direction, George Church’s lab at Harvard has achieved the successful synthesis of functioning ribosomes—the molecular machines that read genetic code and make the proteins for cells.

Today scientists have learned how to write genetic code, and as described by J. Craig Venter, such state-of-the-art biotechnology work is “creating software that makes its own hardware.” Venter said this in 2008 when reporting his team’s successful artificial transformation of one bacterium species into another. The synthesis of ribosomes of your choice is a big deal, because, to borrow computer jargon, it allows you to change the “operating system” when writing new genetic code. The next major step beyond modifying Terran organisms is to create alternative biochemistries and entirely new trees of life.

One example of an alternative biochemistry that is both intuitive and relatively close to fruition is the case of “mirror” life—that is, life with biochemistry essentially identical to our own, but composed of molecules of the opposite chirality, or “handedness.” Terran biochemistry is based exclusively on proteins built from “left-handed” amino acids; for balance, all Terran sugars are right-handed. Scientists understand why organisms can’t be chirally ambidextrous, with equal parts left- and right-handed proteins, but nobody knows whether the left-versus-right choice is a matter of chance or necessity. Alternative ideas to explain Terran life’s left-handedness have been proposed, ranging from a deeply rooted asymmetry in the fundamental forces of nature to astronomical factors like the polarization of starlight. Armed with the newly learned skills to synthesize ribosomes at will, researchers are now attempting to create mirror life in hopes of testing these theories.

But even a simple and somewhat familiar alternative biochemistry like mirror life will not lead to an artificial life form without the necessary next step of “compartmentalization.” This is a fancy way of saying that any self-sustaining biochemistry needs a container to hold it. On Earth, cells are the containers—their semi-permeable membranes encapsulate all the biochemical machinery life needs. Jack Szostak’s lab at Harvard has shown how these membranes can naturally form to create “protocells” and how these protocells can even spontaneously reproduce by splitting into two and more protocells. Szostak’s constructs seem tantalizingly close to real cells. If protocells like these can be reliably paired with a fully-functional mirror biochemistry, the first truly alien life form may not come from a distant planet, but from a petri dish in a research lab. Unless an unexpected obstacle awaits us, this could happen in the next couple of years.

That’s not to say we shouldn’t study distant planets to inform our laboratory studies of alternative biochemistries. Compared to the diversity of possible planetary systems suggested by theoretical models, our own solar system appears to offer a very limited set of planetary geochemical environments for us to sample. Astronomers are now rapidly discovering entirely new classes of planets orbiting other stars. One kind in particular—rocky planets with two to 10 times the mass of Earth—is turning up seemingly everywhere we look. These so-called “super-Earths” probably have characteristics quite different from our own planet, but they may very well be cradles for forms of life with exotic biochemistries. Across the light-years, we may soon study these bizarre planets for global signs of life. These studies will inform our efforts in the lab, and vice versa, in a self-reinforcing process that leads towards understanding the cosmic conditions for life.

Whatever we end up learning, it is bound to transform our world in at least two ways. First, the technology that comes out of it is going to be powerful. Similar to how the 20th century brought us synthesis in chemistry, the 21st is bringing a synthesis in biology, with all the requisite implications for new materials, therapies, industries, and applications we cannot yet predict. The second impact, which has no parallel in synthetic chemistry, is nothing less than a revolution in our understanding of life and its place in the cosmos. It remains uncertain how we shall have to adjust our worldview, as we’ve yet to see whether extraterrestrial life is rare or ubiquitous—but either way, the implications will be earthshaking.

Dimitar Sasselov is the director of the Origins of Life Initiative at Harvard University.


Originally published March 14, 2011

Tags biology biotechnology global reset space

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