Nicholas V. Hud imagines that life evolved from molecules that were the result of chemical reactions that took place at millions of locations, scattered across the landscape of early Earth, each location producing a type of molecule that could grow as chemistry permitted. As the molecules grew, they ‘crept’ across the land in puddles and rivulets, mixing with other sets of molecules. The molecular aggregates became more complex mixtures until, after eons of mingling, the transition from chemistry to biology occurred.
The television show “Star Trek: The Next Generation” has alluded to this scenario. In the series finale, the omnipotent antagonist Q takes the hero, Captain Jean-Luc Picard, back in time to early Earth: a barren wasteland except for small pools of water stretching across the surface. As Picard examines a pool, Q mockingly tells him, “This is you. Right here, life is about to form on this planet for the very first time. Strange, isn’t it? Everything you know, your entire civilization, it all begins right here in this little pond of goo.”
“I thought the whole setting looked as I would imagine it,” says Hud, a professor in the School of Chemistry and Biochemistry.
In Hud, such imagination is coupled with ingenuity and creativity in breaking down large research objectives into smaller ones and attacking those one by one. This—plus a fearlessness in pushing new ideas and a cheery optimism—makes Hud an outstanding professor and scientist. For his achievements so far, the University System of Georgia (USG) last year named Hud a Regents Professor. This honor is the highest bestowed by USG for distinction and achievement in teaching and scholarly research.
Understanding how chemistry begat biology is one of the grand challenges of science. It is the focus of Hud’s research and of the Center for Chemical Evolution (CCE), which Hud directs. The CCE has positioned Georgia Tech as one of the leading institutions in origins-of-life research.
Hud was a graduate student when origins-of-life research was undergoing a renaissance in the early 1990s. “It made me wonder: where did these molecules come from?” says Hud, referring to the biological polymers—RNA, DNA, and proteins—that are central to all the chemistry of life. How did the transition from single molecules to biological polymers occur?
“I had a feeling that it might be possible to address some parts of this problem,” Hud says. “We’ve made good progress within CCE, but we need to do more.”
Origins-of-life research is vast in scope. Hud and CCE are focused on the origins of biopolymers. The origins of nucleic acids, which are DNA and RNA in current life, is a particularly challenging question. It starts with what has been named the “nucleoside problem.”
Unlike amino acids—the building blocks of proteins—which can be produced in relatively simple chemical reactions, nucleosides--the building blocks of nucleic acids—are trickier to make. Each nucleoside has a “base,” which is the pairing part of the molecule, and a sugar, which is ribose in RNA and deoxyribose in DNA. Although ribose and the bases of RNA can be made in model prebiotic reactions, Hud says, it has proven virtually impossible to connect the bases to ribose by reactions that would have likely happened on early Earth.
Instead of using the bases found in modern nucleic acids to figure out how nucleosides may have formed from primordial pools, Hud is looking for different bases that connect easily with a sugar to form a nucleoside.
“If you change just one or two atoms from the molecules that we have in life today, it may be possible to come up with molecules that will easily form RNA-like polymers,” Hud says. “That’s our overarching hypothesis: that life started with slightly different molecules and developed more sophisticated chemistry over time.”
Whether the question of how chemistry gave rise to biology will ever be fully answered, Hud says that CCE research will not only further our understanding of life’s origins, but also reap benefits in other ways. “We are finding reactions for the synthesis of molecules and polymers in water that rival the best of those designed by synthetic chemists,” Hud says. “If we are successful, these molecules and polymers could facilitate the production of useful materials and therapeutics, for example.”
A WACKY IDEA
Research on the nucleoside problem has led Hud to revitalize an old origins-of-life theory, one that counters the “RNA world” idea, which caught fire when Hud was a graduate student. Questioning RNA as the end-all be-all molecule of life, Hud prefers the idea of a series of pools and hotbeds of chemical activity spread over a wide area, all involved in different chemical reactions. In time, the separate pools engage in cross-talk, cooperating and evolving synchronously, until enough components coalesce into membrane-bound cells.
“I think early on there were many different molecules simultaneously making the transition from small molecules to polymers,” Hud says. He thinks of the system as “a giant, distributed organism where the chemistry that we have in cells today was operating over the surface of the land.” As chemistries were evolving in different parts of this “megaorganism,” the pools of chemical activities were sharing solutions to certain problems in the chemistry of what needed to be done to initiate life, Hud explains.
“I like this model of early life where in one place a solution arises that is able to catalyze a reaction that’s needed a kilometer away,” Hud explains. “Some people think this is a wacky idea,” Hud adds with a chuckle. But, he emphasizes, “the theory fits the current data well.”
“Thinking about the wonder and the power of chemistry to give rise to molecules as complex as what we have inside of us is exciting,” Hud says. The drive that moves him toward uncovering the mysteries of the eons also makes him optimistic. Unraveling the steps from chemistry to biology has become a consuming passion that permeates his speech and manner with cheerful positivity.
“Within a few years, we may be able to understand the chemistry that gives rise to life,” Hud says. “In doing that, chemists could use what we learn to make new materials, medicines, and therapeutics. As we understand more about the nature of the universe, I am hopeful that all of us will have a greater appreciation for the special role Earth played in the origins of life, which could result in us making better choices for the world and for society.”
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