By Fazale ‘Fuz’ R. Rana, Hugh Henry and Daniel J. Dyke
“It would not be an exaggeration to say that the origin of life is one of the greatest unanswered questions in science.”1
For nearly six decades the scientific community has labored to explain the origin of life via chemical evolution. Researchers have identified chemical routes that generate the key building blocks of life—amino acids, nucleobases, sugars, and fatty acids—from simple chemical compounds. They've demonstrated how these compounds can assemble into complex, information-rich biopolymers and aggregate into proto-cellular entities. They've used in vitro evolution to evolve RNA molecules with a wide range of functional capabilities. If nothing else, the origin-of-life research community has confirmed the existence of the physicochemical processes and mechanisms needed to get life started. Small wonder many people believe the mystery is close to being solved.
And yet every proposed model for a naturalistic origin of life has met with myriad problems.2 The accomplishments of the researchers are truly impressive—but in reality they represent false successes. To begin with, these experiments lack geochemical relevance. They work well in the laboratory environment, but they do not translate to the conditions of early Earth.
Secondly, these prebiotic simulations fail to take into account the role of the researcher in the experimental design. Hence why some scientists say the origin-of-life problem remains unsolved. In writing about the RNA world hypothesis (one of the most important ideas in the origin-of-life discussion), physicist Paul Davies notes,
As far as biochemists can see, it is a long and difficult road to produce efficient RNA replicators from scratch...This conclusion has to be that without a trained organic chemist on hand to supervise, nature would be struggling to make RNA from a dilute soup under any plausible prebiotic conditions.3
Davies's observation applies to more areas of origin-of-research than just the RNA world hypothesis. And the situation hasn't changed in the 15 years since he penned these words. When scientists perform origin-of-life experiments, they are no longer passive observers of undirected processes. They become active participants. They interject themselves into experiments designed to demonstrate that life can emerge on its own. If poorly executed or too extensive, such involvement runs the risk of making the experiment artificial, no longer true to the evolutionary events thought to have occurred on early Earth.
Such situations better reflect what happens when an intelligent agent (the researchers, in this case) orchestrates physicochemical processes—and we argue that this demonstrates the central role of creative design in the origin-of-life process. Still many in the scientific community would resist any suggestion that life stems from the work of a Mind. One key reason for this resistance relates to a poor of view intelligent design.
In this paper we propose to demonstrate the necessity of intentional agency in the origin of life by examining unwarranted researcher involvement in two prebiotic experiments. Then we will suggest a solution to scientists' reluctance to embrace intelligent design as a legitimate explanation for life's origin.
The Impact of Researcher Intervention on Prebiotic Simulation Studies
Without the option of time travel, scientists must look to other methods of research to understand how undirected chemical and physical processes could have generated life. It's possible to probe the ancient geochemical record for clues; however, such efforts have only allowed researchers to "look through the glass, dimly." Likewise, the geochemical records of the planet's oldest rocks have provided key insight about the chemical resources available on early Earth and the likely geochemical and biochemical activities of that time—but the picture is incomplete at best and often muddled.4
Thus researchers have no choice but to go into the laboratory and do experiments with the overarching goal of recapitulating the origin of life. And if they can't do that, then the most they hope can for is that their work provides some understanding of how life could have conceivably emerged on Earth—apart from the work of an intelligent agent.
But these scientists face a conundrum. Excessive researcher intervention could render origin-of-life experiments irrelevant and yet some involvement is necessary even if just to set up the experiment. They have to design the protocol, assemble the apparatus, supply the media and reagents for the experiment, adjust the initial conditions and regulate them throughout the study, and monitor the course of the chemical and physical changes usually by withdrawing material from the apparatus.
At what point does researcher involvement become illegitimate? At what point does the experiment transform from one that provides important insight to one that has questionable relevance?
Such concerns should necessitate including a critical assessment of researcher involvement in the interpretation of results from origin-of-life experiments.5 Yet such evaluation is seldom mentioned when scientists reflect on the success (or failure) of these experiments. In fact, more often than not, they simply ignore any impact that the investigators may have had on the outcome. As a consequence of this oversight, it often appears as if origin-of-life researchers are closer to accounting for life’s start than they may actually be. Two examples related to the RNA world hypothesis illustrate this problem.
Researcher Intervention and the RNA World Hypothesis
As the late origin-of-life investigator Leslie Orgel noted, "It may be claimed, without too much exaggeration, that the problem of the origin of life is the problem of the origin of the RNA World."6
Many origin-of-life investigators think that RNA predated both DNA and proteins as the premier replicator and information-harboring molecule. Accordingly, RNA operated as a self-replicator that catalyzed its own synthesis. The RNA world hypothesis supposes that numerous RNA molecules—representing a wide-range of catalytic activity—emerged over time. At this point in life's history biochemistry centered exclusively on RNA. With time, proteins (and eventually DNA) joined RNA in the cell's replication and informational arsenal. During the transition to the contemporary DNA-protein world, RNA's original function became partitioned between proteins (replication) and DNA (information storage), and RNA assumed its current intermediary role. RNA ancestral molecules presumably disappeared without leaving a trace of their primordial existence.
The RNA world hypothesis hinges on researchers establishing the validity of several processes.
- Reasonable prebiotic chemical routes that will generate RNA’s building blocks (nucleobases, ribose, and phosphate)
- Reasonable prebiotic routes that will assemble these building blocks into ribonucleotides
- A realistic reaction scheme that will chemically activate the ribonucleotides
- Reasonable prebiotic routes that will assemble RNA from its building blocks into molecular chains long enough to form ribozymes
- Demonstration that ribozymes possess a range of catalytic activities necessary to sustain an RNA-based biochemistry
- Production of an RNA self-replicator
According to Orgel, "The synthesis of nucleosides from ribose and the nucleobases is the weakest link in the chain of prebiotic reactions leading to oligonucleotides."7 For decades chemists have struggled to discover a way to make ribonucleotides by directly reacting ribose with the pyrimidine nucleobases (uracil and cytosine). Researchers have been able to make ribonucleotides using purines, however, by heating these compounds with ribose and certain salts, like magnesium chloride. Unfortunately, these reactions are highly inefficient. Yields of purine nucleotides comprise only two to five percent of the total complex mixture.
Intermingling Prebiotic Routes
Recently, a team of chemists from the University of Manchester discovered a possible way around this serious problem. Instead of dividing possible prebiotic reactions into those that lead to sugars and those that lead to nucleobases, and then trying to find a way for the sugars and nucleobases to combine to form ribonucleotides, the team took a different tact. They looked for ways that the two prebiotic routes could intermingle.
This novel approach led to a breakthrough. The University of Manchester team discovered that activated ribonucleotides could be readily formed in the laboratory in just a few simple steps.8 (This process is known as the Sunderland reaction scheme.) The reaction of cyanamide and glycoaldehyde to form 2-amino-oxazole is key to this prebiotic sequence. (Traditionally, scientists view cyanamide as part of the chemical pathways to some of the nucleobases; glycoaldehyde is the first product in the formaose reaction.) In turn, 2-amino-oxazole reacts with glyceraldehydes (formed when glycoaldehyde reacts with formaldehyde) to form a sugar derivative called pentose amino-oxazoline. This compound reacts with cyanoacetylene (one of the starting materials in the prebiotic synthesis of cytosine) to generate anhydroarabinonucleoside, which can react with pyrophosphate and urea to form an activated ribonucleotide. Finally, activated ribonucleotides are poised to react with each other to form RNA chains.
As promising as this chemistry is, the researchers noted a serious problem. In unbuffered reactions—in which the pH is uncontrolled—a large number of products result at each step in the pathway. As a consequence, 2-amino-oxazole is only present in the system at low levels. The other unwanted products interfere with the remainder of the pathway, frustrating the generation of activated ribonucleotides.
In the face of this problem, the researchers discovered that including phosphate in the reaction mixtures eliminated many of the unwanted byproducts. Phosphate functions as both a catalyst and a buffer, controlling the pH of the reaction mixture. In other words, one of the key reactants in the last stage of the chemical route plays a role in earlier reactions. The researchers also discovered that exposing the final reaction mixture to UV radiation selectively destroys unwanted byproducts as well.
Without question, the University of Manchester chemists have contributed an important conceptual advance to origin-of-life research, and possibly to the evolutionary paradigm. Their work paves the way for others to approach problems in prebiotic chemistry in an unconventional way that might lead to other breakthroughs. Still, have they really rescued the RNA world hypothesis? In spite of this work's apparent success, problems abound.
1. Only half a solution. No route exists to make two of the four ribonucleotides needed to make RNA molecules. This reaction scheme only works for ribonucleotides that consist of pyrimidines. In other words, the origin-of-life community is only part way to resolving the problems concerning the source of activated ribonucleotides.
2. Possible side reactions. Even though the researchers examined ways that proposed prebiotic routes could intermingle, they still didn't take into account all of the possible side reactions that could frustrate the reaction sequence they discovered. For example, the researchers ignored all the reactions that would competitively destroy cyanoacetylene and cyanoacetaldehyde, two key components in this pathway. The researchers conducted their laboratory experiments using purified chemicals and carefully controlled the compounds added to the reactions. But if unguided evolution were true, then this level of control would never have been present on early Earth.
3. Unselective UV radiation. Yes, exposure to UV radiation helps selectively destroy contaminants in the last step of the reaction, but in the earlier steps of the process it would indiscriminately destroy all of the reactants. The researchers were able to control when the mixture was exposed to UV radiation—but this type of selectivity wouldn’t be available on the early Earth. UV radiation from the Sun would have impinged on early Earth continuously.
4. Highly reactive ribonucleotides. If chemically-activated ribonucleotides don't form, then RNA chains can't assemble. And unfortunately, chemically activated ribonucleotides are highly reactive. Other materials present on early Earth would have quickly consumed these compounds, making it unlikely that these materials would have existed at levels high enough to help the RNA world scenario. It's a no-win situation.
5. Unavailable phosphate. Perhaps the most significant problem has to do with the process's dependence on phosphate. The high levels of phosphate used in the lab simply wouldn't have been present on early Earth.
The University of Manchester chemists have done a masterful job, in principle, of indentifying a chemical route that could have generated two of the four ribonucleotides. They also went a long way toward ferreting out the chemical mechanisms that dictate the reaction sequence. But they have failed to demonstrate this chemical pathway's geochemical relevance. The conditions required to make this reaction sequence work wouldn't have been present on early Earth.
Clay Catalysts for RNA Assembly
Another false success for the RNA world hypothesis came from the assembly of RNA chains on clay surfaces. In the mid-1990s, James Ferris and his research team stirred excitement within the scientific community by assembling lengthy RNA molecules from ribonucleotides activated as phosphorimidazolides, using clay as a catalyst. They accomplished this assembly by washing solutions of the reactants over clay surfaces and then allowing the solutions to evaporate.9 Commentators heralded this work as a key demonstration that prebiotic conditions could have produced self-replicators.10 However, closer evaluation of this effort prompts a different conclusion.
1. Selective conditions. Origin-of-life scientist Robert Shapiro pointed out that Ferris's teams conducted these experiments under selective conditions that excluded potential chemical interferents, ignoring what Shapiro deems the homopolymer problem.11 It is highly unlikely that activated ribonucleotides would have been formed under the prevailing conditions of early Earth.12 (And, as already noted, even if these materials had formed, their high reactivity would have caused them to combine with all sorts of compounds present on early Earth, and, thus, frustrate the generation of RNA molecules.)
Additionally, Shapiro noted a problem of excessive selectivity associated with the clay itself. Ferris's teams used clay known as montmorillonite. This clay is widely distributed throughout the Earth, but not all montmorillonite clays are equal. A clay's success as a catalyst depends on the location it comes from. Ferris and his collaborators found that clay provided by the American Colloid Company, which sources its clays from Wyoming, has the best likelihood of generating RNA molecules.13 The American Colloid Company processes their clays (Volclay) before delivery to the customer.
On top of that, the Ferris teams also had to pretreat the clays before using them as catalysts because the copper, iron, and zinc ions normally associated with the clays interfere with RNA assembly and the oligomerization reactions won't happen. The offending materials are removed by a special procedure called a titration and replaced with benign sodium.14 Obviously, unassisted chemical evolution would not have been able to ensure successful RNA generation through such treatments and selectivity.
2. Mineral surfaces. Meanwhile, Leslie Orgel's teams noted that mineral surfaces can also catalyze RNA’s decomposition.15 For example, RNA breakdown occurs on surfaces of minerals that contain lead and calcium. Orgel's teams discovered that the amino acids glutamate and histidine stimulate the breakdown of RNA in a solution. Additionally, a Japanese team demonstrated that rare Earth elements (like cerium) present in the primordial oceans would have catalyzed the breakdown of the RNA backbone linkage.16 Proteins can prevent the breakdown of RNA, but the inhibition of this cleavage would have required an unrealistically high level of proteins in the early oceans.
Another difficulty for mineral-assisted RNA formation is the irreversible attachment of RNA to mineral surfaces once the molecular chain grows to a certain length. On early Earth, this attachment would have prevented the RNA molecule formed on a clay surface from being available for the origin-of-life process.
3. Problematic reaction mechanism. In the laboratory, Orgel and colleagues have demonstrated that once an RNA chain exists, it can serve as a template for assisting the assembly of another RNA chain. These experiments made use of activated ribonucleotide phosphorimidazolides to promote the reaction between ribonucleotides (others used condensing agents).17 These reactions can take place in fairly dilute solutions. But at least two problems exist when this mechanism is considered in the context of early Earth's environment: (1) chemical interferents would have most certainly interrupted chain formation; and (2) the presence of racemic mixtures of ribonucleotides would have frustrated chain assembly. Thus, Orgel's team has demonstrated that the incorporation of opposite-handed nucleotides disrupts RNA chain formation in template-assisted formation of RNA chains.18
4. Chain length. RNA chains are inherently unstable. As individual building block molecules are added to the chain causing it to grow in length, water molecules react with the RNA (a process called hydrolysis), breaking the chain down. In other words competing reactions of growth and degradation would prevent the chains from attaining the requisite length to generate a ribozyme.
Just like the chemists from the University of Manchester, James Ferris and other origin-of-life researchers have done a masterful job of identifying chemical processes that generate RNA molecules, in principle. But they have failed to demonstrate that these processes have geochemical relevance. The conditions required for RNA assembly on clay wouldn't have been present on early Earth.
Researcher Intervention and the Case for Intelligent Design
We’d argue that researchers working to understand the RNA world hypothesis have provided empirical evidence an intelligent agent is necessary to direct prebiotic chemistry in such a way so as to affect the origin of life. In the case of the Sunderland reaction scheme, the chemists: (1) carefully controlled the amounts and purity of the chemical components added to the reaction mixtures; (2) adjusted the reaction conditions, which includes adding the appropriate level of phosphate; and (3) selectively exposed the final reaction products to UV radiation as a way to get rid of unwanted byproducts. Without this interference, the generation of activated ribonucleotides would have been impossible.
Shaprio comments, "The flaw with this kind of research is not in the chemistry. The flaw is in the logic—that this experimental control by researchers in a modern laboratory could have been available on the early Earth."19 Likewise, the laboratory simulation experiments that Ferris's teams used to synthesize RNA on mineral surfaces differ substantially from early Earth's conditions. When scientists consider more realistic scenarios, they discover that RNA assembly could not have occurred naturally in the prebiotic realm to any appreciable extent.
Hypernaturalism and Intelligent Design
A remarkable number of scientists would agree with our critique—yet they resist any suggestion that life's origin stems from the work of a divine Mind, in part because of how many scientists view the Intelligent Design Movement. They regard an appeal to intelligent agency as an appeal to the supernatural and, thus, a strict violation of the principle of methodological naturalism—the philosophical framework undergirding the scientific enterprise. According to this view, all scientific models require mechanistic explanations. Any appeal to the work of an intelligent agent is forbidden.
The concept of “hypernaturalism,” proposed by Daniel J. Dyke and Hugh Henry, provides a means to address the concerns of the scientific community.20 “Supernaturalism” argues that God operates outside the laws of nature when He enacts a miracle, whereas in hypernaturalism, as defined by Dyke and Henry, God employs the laws of nature and phenomena in the nature in an extraordinary manner—with respect to timing, location, and magnitude—to accomplish His will. (See Dyke and Henry’s article “Hypernaturalism: Integrating the Bible and Science” for more detail.)
Through the use of hypernaturalism, the dichotomy between natural process chemical evolution and Intelligent Design largely disappears. Instead, the origin of life can be seen to arise via hypernatural processes in which the Creator makes use of well-understood physicochemical mechanisms to affect the origin-of-life. In this schema, the origin-of-life does not arise via the suspension of the laws and processes of nature but through them. The origin of life is a second stage interventionist miracle in which God intervenes within the created laws of nature (not a first stage miracle, in which God operates outside the laws of nature). The point of applying hypernaturalism to the origin-of-life scenario is not to compromise a Christian’s position on God’s creative power, but to find as much common ground as possible with researchers and to avoid dismissing their hard work in the lab.
Hypernaturalism addresses another concern of the scientific community: namely, Intelligent Design (conceived as supernatural interference) stultifies the scientific process. If a Creator brought life into existence “supernaturally,” then there is nothing for scientists to study. On the other hand, thinking of the origin-of-life as the result of God’s hypernatural action makes it possible for scientists to investigate the origin-of-life question within the framework of methodological naturalism, even if life’s emergence is understood to be a miracle.
In essence, when origin-of-life researchers perform prebiotic simulation experiments, they operate in a hypernatural way, too. They control the experimental set up and laboratory conditions to bring about extraordinary circumstances—within the confines of the laws of nature and natural processes—that bring about key steps in the pathway to the origin of life.
Could it be that God functioned like a divine organic chemist when He brought life into existence? In light of this question, it is intriguing that the Judeo-Christian Scriptures describe humans as made in God’s image. If that is the case, then when we create—or when humans step into the laboratory to run a chemical reaction—are we mimicking, though imperfectly, the Creator?
We would submit that the answer to these two questions is yes.
We maintain that the prebiotic simulation studies carried out over the course of the last six decades not only demonstrate that life’s origin requires a Creator, but they also give insight into how God did it.