Sometimes tectonic shifts in scientific disciplines occur because of discoveries and advances in the field. But sometimes they occur for reasons entirely outside the field itself. Such appears to be case with origins-of-life studies.
Nobel laureate Jack Szostak was recently in Tokyo to participate in a workshop at the Earth-Life Science Institute (ELSI) at the Tokyo Institute of Technology on “Reconstructing the Phenomenon of Life To Retrace the Emergence of Life.”
The talks were technical and often cutting-edge, but the backstory that Szostak tells of why he and so many other top scientists are now in the origins of life field was especially intriguing and illuminating in terms of how science progresses.
Those ground-shifting discoveries did not involve traditional origin-of-life questions of chemical transformations and pathways. They involved exoplanets.
“Because of the discovery of all those exoplanets, astronomy has been transformed along with many other fields,” Szostak said after the workshop.
“We now know there’s a large range of planetary environments out there, and that has stimulated a huge amount of interest in where else in the universe might there be life. Is it just here? We know for sure that lots of environments could support life and we also would like to know: do they?
“This has stimulated much more laboratory-based work to try to address the origins question. What’s really important is for us to know whether the transition from chemistry to biology is easy and can happen frequently and anywhere, or are there one or many difficult steps that make life potentially very rare?”
In other words, the explosion in exoplanet science has led directly to an invigorated scientific effort to better understand that road from a pre-biotic Earth to a biological Earth — with chemistry that allows compounds to replicate, to change, to surround themselves in cell walls, and to grow ever more complex.
With today’s increased pace of research, Szostak said, the chances of finding some solid answers have been growing. In fact, he’s quite optimistic that an answer will ultimately be forthcoming to the question of how life began on Earth.
“The field is making real progress in understanding the pathway from pre-biotic chemistry to the earliest life,” Szostak told. “We think this is a difficult but solvable problem.”
And any solution would inevitably shed light on both the potential make-up and prevalence of extraterrestrial life.
Whether it’s ultimately solvable or not, that pathway from non-life to life would appear to be nothing if not winding and complex. And since it involves trying to understand something that happened some 4 billion years ago, the field has had its share of fits and starts.
It is no trivial fact that probably the biggest advance in modern origin-of-life science — the renown Miller-Urey experiment that produced important-for-life amino acids out of a sparked test tube filled with gases then believed to be prevalent on early Earth — took place more than 60 years ago.
Much has changed since then, including an understanding that the gases used by Miller and Urey most likely did not reflect the early Earth atmosphere. But no breakthrough has been so dramatic and paradigm shifting since Miller-Urey. Scientists have toiled instead in the challenging terrain of how and why a vast array of chemicals associated with life just might be the ones crucial to the enterprise.
But what’s new, Szostak said, is that the chemicals central to the pathway are much better understood today. So, too, are the mechanisms that help turn non-living compounds into self-replicating complex compounds, the process through which protective yet fragile cell walls can be formed, and the earliest dynamics involved in the essential task of collecting energy for a self-replicating chemical system to survive.
This search for a pathway is a major international undertaking; a collective effort involving many labs where obstacles to understanding the origin-of-life process are being overcome one by one.
Here’s an example from Szostak: The early RNA replicators needed the element magnesium to do their copying. Yet magnesium destroyed the cell membranes needed to protect the RNA.
A possible solution was to find potential acids to bond with magnesium and protect the membranes, while still allowing the element to be available for RNA chemistry. His team found that citric acid, or citrate, worked well when added to the cells. Problem solved, in the lab at least.
The Szostak lab at Harvard University and the Howard Hughes Medical Institute has focused on creating “protocells” that are engineered by researchers yet can help explain how origin-of-life processes may have taken place on the early Earth.
Their focus, Szostak said, is on “what happens when we have the right molecules and how do they get together to form a cell that can grow and divide.”
It remains a work in progress, but Szostak said much has been accomplished. Protocells have been engineered with the ability to replicate, to divide, to metabolize food for energy and to form and maintain a protective membrane.
The perhaps ultimate goal is to develop a protocell with with the potential for Darwinian evolution. Were that to be achieved, then an essentially full system would have been created.
Just as the discovery of a menagerie of exoplanets jump-started the origin of life field, it also changed forever its way of doing business.
No longer was the field the singular realm of chemists, but began to take in geochemists, planetary scientists, evolutionary biologists, atmospheric scientists and even astronomers (one of whom works in Szostak’s lab.)
“A lot of labs are focused on different points in the process,” he said. “And because origins are now viewed as a process, that means you need to know how planets are formed and what happens on the planetary surface and in the atmospheres when they’re young.
“Then there’s the question of essential volatiles (such as nitrogen, water, carbon dioxide, ammonia, hydrogen, methane and sulfur dioxide); when do they come in and are they too much or not enough.”
These were definitely not issues of importance to Stanley Miller and Harold Urey when they sought to make building blocks of life from some common gases and an electrical charge.
But seeing the origin of life question as a long pathway as opposed to a singular event leaves some researchers cold. With so many steps needed, and with the precisely right catalysts and purified compounds often essential to allow the next step take place, they argue that these pathways produced in a chemistry lab are unlikely to have anything to do with what actually happened on Earth.
Szostak disagrees, strongly. “That just not true. The laws of chemistry haven’t changed since early Earth, and what we’re trying to understand is the fundamental chemistry of these compounds associated with life so we can work out plausible pathways.”
If and when a plausible chemical pathway is established, Szostak said, it would then be time to turn the scientific process around and see if there is a possible model for the presence of the needed pathway ingredients on early Earth.
And that involves the knowledge of geochemists, researchers expert in photochemistry and planetary scientists who have insight into what conditions were like at a particular time.
Given the work that Szostak, his group and others have done to understand possible pathways that lead from simple starting materials to life, the inevitable question is whether there was but one pathway or many.
Szostak is of the school that there may well have been numerous pathways that resulted in life, although only one seems to have won out. He bases his view, in part at least, on a common experience in his lab. He and his colleagues can bang their collective heads together for what seems forever on a hard problem only to later find there was not one or two but potentially many answers to it.
An intriguing implication of this “many pathways” hypothesis is that it would seemingly increase the possibility of life starting beyond Earth. The underlying logic of Szostak’s approach is to find how chemicals can interact to form life-like and then more complex living systems within particular environments. And those varied environments could be on early Earth or on a planet or moon far away.
“All of this looked very, very hard at the start, trying to identify the pathways that could lead to life. And sure, there are gaps remaining in our understanding. But we’ve solved a lot of problems and the remaining big problems are a rather small number. So I’m optimistic we’ll find the way.”
“And when we get discouraged about our progress I think, you know, life did get started here. And actually it must quite simple. We’re just not smart enough to see the answer right away.
“But in the end it generally turns out to be simple and you wonder 20 years later, why didn’t we think of that before?”