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What Came Before the Chicken or the Egg? By T.J. Becker, illustration by David Curtis

What Came Before the Chicken or the Egg?

text - In their quest to understand the origins of life,

scientists have been able to produce small molecules by modeling chemical reactions that could have occurred on early Earth. Yet, the larger question remains: How did these simple molecules give rise to the functional biopolymers and complex structures found in today’s living cells?

That’s the mystery researchers at the Center for Chemical Evolution (CCE) are trying to unravel.

Chemical evolution is different from biological evolution, which is how species that reproduce change over time and adapt to their environment.

“In contrast, chemical evolution refers to changes in molecules that aren’t dependent on reproduction or genetics,” explained Nicholas Hud, director of the CCE and a professor in Georgia Tech’s School of Chemistry and Biochemistry. “For example, polymers (large molecules that are chains of smaller molecules) can become more refined in their structure and gain some ability to catalyze chemical reactions. Although simpler than biological evolution, we believe the ability for certain polymers to evolve in this way was key to getting life started.”

CCE launched in 2010 with a $20-million, five-year grant from the National Science Foundation and NASA, and, in October 2015, funding was renewed for another five years. The center’s multi-institutional team is led by Georgia Tech and includes research groups from the University of South Florida, Furman University, Jackson State University, Kennesaw State University, the Scripps Institution of Oceanography, the Scripps Research Institute, the SETI Institute, and Spelman College.

“A big part of our research strategy is to embrace the concept that molecules on prebiotic Earth were probably not limited to those found in life today,” Hud said. With that in mind, CCE researchers set out to investigate a broader inventory of molecules that may have been present on early Earth and conditions that could have helped these small molecules form highly ordered assemblies and polymers.

In the past five years, CCE researchers have made a number of important advances toward understanding the environments and molecules that may have given rise to the first polymers of life. Of particular significance, they have demonstrated how molecules that were likely present on early Earth promote the formation of polymers very similar to those found in today’s living organisms. In addition to pushing the envelope of prebiotic chemistry, some of the researchers’ advances have implications for modern analytical and green chemistries.

photo - Nick Hud

Nicholas Hud is a professor in Georgia Tech’s School of Chemistry and Biochemistry, and director of the Center for Chemical Evolution.


In a major discovery this summer, CCE researchers found a more plausible prebiotic reaction that causes simple amino acids to form peptides, which are smaller versions of proteins.

In the past, origins-of-life researchers have made short peptides, but this required high temperatures or using activating chemicals to drive amino acid polymerization. Yet, there are reasons to doubt that these scenarios would have occurred on early Earth, Hud says. Taking a different approach, CCE researchers mixed hydroxy acids with the amino acids and then subjected the mixture to wet-dry cycles — a process that is not only simpler but yielded far better results.

illustration - detail of cover

Combining hydroxy acids with amino acids is important, Hud says, explaining that similar experiments with just amino acids didn’t generate peptides. Introducing hydroxy acids results in the formation of ester bonds, lowering the energy barrier enough for peptide bonds to form. “At temperatures believed to have been prevalent on early Earth, the energy barrier to make a peptide bond is simply too high,” said Hud. “Ester bonds act as a sort of halfway point on the way to peptide formation. If an ester bond is formed first, it’s like a stepping stone from which a peptide bond can form.”

The wet-dry cycles as a vehicle to drive polymerization is appealing because they mimic conditions that happen on Earth today: nighttime cooling and dew formation followed by daytime heating and evaporation. In addition, earlier studies have shown that amino acids and hydroxy acids are found together in some meteorites, so these molecules could have co-existed on early Earth and in many places around the universe.

“You can think of a realistic scenario where meteorites bring in these chemicals, and with the sun shining and rain falling, the wet-dry cycles would naturally lead to the conversion of these amino and hydroxy acids into depsipeptides (polymers containing both amino and hydroxy acids), and then, as they continue to recycle, grow into peptides,” pointed out Ramanarayanan Krishnamurthy, a member of the research team and an associate professor of chemistry at the Scripps Research Institute. “You don’t have to invoke any magic or any special chemical or circumstances; this could have naturally occurred on early Earth.”

Other recent milestones include:

  • Identifying ancestors of RNA. Many researchers believe that ribonucleic acid (RNA), a close chemical relative of DNA, was the first polymer of life. In studying RNA origins, scientists have struggled to find the chemical reaction that would have initially formed the bond between the bases of RNA and ribose, the sugar that is part of the RNA polymer backbone. Working with a molecule called triaminopyrimidine (TAP), which is similar to the bases of RNA, CCE researchers discovered that TAP forms a bond with ribose when subjected to wet-dry cycles. Then when researchers introduced cyanuric acid (another molecule that could have been present on early Earth), the ribose-linked TAP and cyanuric acid molecules assembled into structures that resemble the structure of RNA. “These are non-covalent polymers, so we still need to produce more stable polymers that are held together by covalent bonds,” Hud said. “Yet, these results may already be telling us how the earliest molecules of life could have found each other in a messy soup of molecules on prebiotic Earth.”
  • Strides toward polysaccharides. Alternative sources of sugars have not been heavily investigated in prebiotic chemistry. Until recently, the only proposed building block for polysaccharides has been formaldehyde, which after being subjected to a number of chemical transformations can result in complex sugars like ribose, needed for RNA. The drawback, however, is that yields are quite low. Yet, a team of CCE researchers led by Krishnamurthy and Charles Liotta, a Regents Professor Emeritus in Georgia Tech’s School of Chemistry and Biochemistry, has discovered that glyoxylate is a better starting point. When combined with dihydroxyfumarate (DHF) and other prebiotic chemicals, glyoxylate undergoes a series of reactions and produces ketoses, which can be converted into ribose under the right conditions. “The advantages of glyoxylate over formaldehyde are that the pathway is far more efficient, and there are few side reactions,” said Krishnamurthy. The researchers have also discovered that the same reactants produce dramatically different products just by changing the pH of the reaction solution. “When we do certain reactions near a neutral pH, we get a suite of products that are important biologically, but when we change the pH to something more alkaline, another suite of products is formed, which is also biologically important,” Liotta explained. “That tells us we have to be really cognizant of the environment in which we carry out our reactions — that a simple change to the pH in a solution can drastically change what happens reaction-wise.”
  • Phosphorylation sans enzymes. A group of CCE researchers led by Matt Pasek, an associate professor of geochemistry at the University of South Florida, has found that phosphorylation — a chemical reaction necessary for all forms of life — could have occurred without enzymes, which weren’t present on prebiotic Earth. Pasek’s team has identified minerals in meteorites with phosphide compounds that can spontaneously phosphorylate molecules under certain conditions.


NSF funds eight other Centers for Chemical Innovation (CCI), however, CCE is the only one jointly funded with another federal agency, NASA. “The NASA Astrobiology Program is keenly interested in what we’re doing because it fits in very well with their mission to determine if there is life on other planets,” said Hud.

Although other CCIs are pursuing specific applications, such as solar fuels and sustainable materials, CCE is focused on basic science and understanding prebiotic reactions. The latter is particularly challenging because it restricts the type of molecules and chemistries that CCE researchers can work with.

illustration - detail of cover

For example, biology uses enzymes to facilitate reactions. “Yet, enzymes are made from proteins, and finding the origins of protein is one of our central research questions,” observed Martha Grover, a professor at Georgia Tech’s School of Chemical & Biomolecular Engineering.

Since enzymes were off limits, the researchers had to find alternative building blocks and reactions to make desired polymers under prebiotic conditions. “Now that we have a better hold on the chemistry, we’re ready to build a system that demonstrates the ability of these chemicals to evolve in a pre-biotically plausible environment,” Grover said.

“Right now, we are driving reactions in a glass vessel, but four billion years ago, there was no glass vessel,” pointed out Krishnamurthy. “The question is what sort of context, metals, temperatures, and humidity would have been present to affect a reaction, which means moving on to experiments where we make the mixtures more complex, and environmental conditions more believable. Of course, that raises the bar because there are more variables to control and the reactions produce more products. So, we’re ratcheting up the complexity of what we are looking at.”

Mineral surfaces might have functioned as the first reaction “vessels,” so CCE researchers, led by Thomas Orlando, a professor at Georgia Tech’s School of Chemistry and Biochemistry, are also investigating how different minerals can alter the products of model prebiotic reactions.


Although CCE researchers are focused on expanding the knowledge base of prebiotic chemistry, there are some practical applications to today’s world, especially in the line of chemical analysis technology.

“A large part of the center’s effort goes into analyzing very complex mixtures of chemicals,” explained Facundo Fernández, a professor in Georgia Tech’s School of Chemistry and Biochemistry. “Imagine taking something that looks like crude oil, which has thousands of different molecules and then identifying what those molecules are. We’ve had to develop tools and techniques to do that not only in a quantitative manner, but also faster and more selectively to avoid false positives.”

illustration - detail of cover

Among analytical milestones, Fernández has shown that polymers (especially those derived from malic acid) can be used for calibrating high-end mass spectrometers and making these sophisticated instruments even more accurate. “This is important because mass spectrometers measure molecules on a relative scale that can drift over time,” said Fernández. “By using these polymers as references, we can set this scale true. In addition, the polymers we describe are cheaper and easier to obtain than traditional calibrants.”

These analytical tools and techniques could be used in a wide variety of applications ranging from detecting explosives for homeland security to finding contaminants in food production.

The reactions and processes that CCE is developing also have potential commercial and industrial applications. For example, while investigating a pathway to primitive nucleic acids, CCE researchers developed a water-free solvent system that can improve assembly of DNA nanostructures. This alternative solvent, a mixture of glycerol and choline chloride, enables more complicated designs with DNA and could prove useful in DNA-based nanotechnology applications where water would interfere with the functioning of a device.

Understanding chemical evolution could open the door for significant advances in polymer chemistry, Hud said.

“Scientists have been able to do a lot of amazing things, but life still is the best chemist,” he explained. “Nucleic acids, proteins, and polysaccharides are amazing materials because they have the ability to evolve or to be evolved. If we can understand how this first happened in life, then we could use the same principles to make new types of polymers, including ones with catalytic abilities.”


And though collaboration is critical in academic research, CCE has taken it to a new level. Enthusiasm runs high among the more than 50 professors, postdocs, and graduate students who work within the center, which they attribute in part to the compelling research topic but also to the unusual camaraderie.

“The center is filled with people who are not only great scientists, but also easy to work with,” said Eric Parker, a graduate student in Georgia Tech’s School of Chemistry and Biochemistry. “Although beneficial to scientists of all ages and experience levels, I think it’s especially important for early career scientists to be exposed to this type of collaborative environment.”

“It’s one thing to have individual grants but quite another to have a center that functions as such,” observed Fernández. “There are many moving parts involved, and scientists from very different backgrounds who literally speak different scientific languages. Yet, we’ve been able to come together and make the center more than the sum of its parts.”

In fact, participating in the center has changed him as a scientist, Fernández added: “We are working on very big questions that transcend our individual fields. Yet, we’re all adapting to whatever we need to be to answer the questions. The center has taken all of us in directions we never anticipated.”


T.J. Becker is a freelance writer based in Michigan. She writes about business and technology issues.


Education is an important component of the Center for Chemical Evolution (CCE). “An increasing number of public and personal decisions rely on technical information, and yet our country has a problem with science literacy,” said Christopher Parsons, director of CCE’s education outreach and diversity. “The subject of chemical evolution and where we came from is a unifying way to excite people about science and to improve their appreciation and literacy.”

In addition to communicating research findings through traditional educational venues, CCE collaborates with a wide variety of artists including painters, sculptors, musicians, animators, and dancers to explain the concept of chemical evolution. Some examples:


Developed in collaboration with Jon Perry, founder of Stated Clearly, CCE has created animated videos about chemical evolution. Three are available online, including a Spanish version.


Performed in March at the Atlanta Science Festival, this trio of dances included an aerial duet based specifically on CCE research. The duet, which took place on a giant aluminum double helix, explored how natural environmental cycles lead to the formation of proto-biopolymers.

photo - dancers performing on a large double helix sculpture
Performance of "Emergence in Motion." Photo: CCE


Working with science journalist Ari Daniel, CCE has developed a series of audio stories about chemistry called Small Matters. The stories are available online and have been picked up by radio stations around the country.

illustration - small matters topics


Steve Everett, one of the center’s early artists-in-residence (now dean of the University of Illinois-Chicago’s College of Architecture, Design, and the Arts), composed First Life, based on an early CCE research paper. The 75-minute multimedia work combines music for a string quartet with video elements.


At this year’s Atlanta Science Festival, the center hosted a booth where Georgia Tech graduate students David Fialho and Christine He drew caricatures of children as scientists. “Some were depicted as astronauts, some had computers, and others were hanging out with lizards,” Parsons said. “The idea was to help children identify as scientists and move beyond stereotypes of white lab coats and crazy hair.”

photo - Christine He with sketches
Georgia Tech graduate student Christine He with her caricatures of children. Photo: CCE

Chemistry and the arts may seem like a stretch, but artists have connected quickly with CCE, said Martha Grover, a professor at Georgia Tech’s School of Chemical & Biomolecular Engineering and faculty lead for the center’s outreach program.

“Many nonscientific ideas about evolution revolve around a survival-of-the-fittest theme: that there’s a single winner in biology,” she explained. “To the contrary, we don’t have just one kind of molecule in our body that outcompeted others — very diverse molecules perform very different tasks. Artists readily engage with the concept of diversity and cooperation being important in evolution in order to build more complicated system behavior.”


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