A Fork in the Road, Part 2 of 2

A Fork in the Road, Part 2 of 2

No Good Options for the Origin of Life

Origin-of-life investigators adopt one of two fundamental approaches to explain life’s beginning: (1) replicator-first, and (2) metabolism-first scenarios. Chemist Robert Shapiro argues in the cover article of the June 2007 issue of Scientific American that the replicator-first approach to the origin-of-life is a failed paradigm. From his vantage point, metabolism-first scenarios offer the best hope to explain the origin of life.

Last week I explained how Shapiro reached this conclusion. This week I will briefly outline Shapiro’s proposal for life’s origin and point out some of the chemical difficulties with all metabolism-first models.


Some origin-of-life researchers postulate that once prebiotic materials formed, these relatively small molecules self-organized to form chemical cycles and networks of chemical reactions that—over time—gave rise to life’s metabolic systems. Once encapsulated or sequestered within a membrane, these complex, reticulated systems of reactions became the first prebionts.

According to this view, molecular self-replicators emerged later along with the enzymes that catalyzed each step in the chemical cycles and networks. Some proponents of metabolism-first scenarios maintain that these cycles and networks closely resembled the metabolic pathways found in the cell today. In other words, “metabolism recapitulates biogenesis.” Metabolism-first adherents suggest that either (1) individual chemical species that were part of these cycles and networks catalyzed these same reactions—a type of autocatalysis; or (2) that mineral surfaces catalyzed the protometabolic pathways.

Shapiro identifies five requirements for all metabolism-first scenarios.

  1. The emergence of a boundary to segregate the proto-metabolic pathways from the environment
  2. An energy source to power the proto-metabolic interactions
  3. A coupling mechanism that links the available energy to the proto-metabolic pathways
  4. The emergence of a chemical network comprised of interconnected cycles of reactions among small molecules
  5. A means for the network to grow and reproduce

Problems with Metabolism-First Scenarios

Even though seemingly plausible, metabolism-first models have only superficial merit.

  1. Most metabolism-first scenarios, including the one proposed by Robert Shapiro, are theoretical ideas with minimal, if any, experimental support. It is easy on paper to have hypothetical compound A convert into B, releasing energy that couples to the conversion of C to D and then D to E. And then have E catalyze the conversion of C to D and so forth. It is another matter to identify compounds that will behave that way in the laboratory, let alone in the environment of early Earth. Origin-of-life researcher Leslie Orgel points out that cycles and networks operating on the early Earth would have been highly susceptible to disruption by chemical interferents and competing side reactions.

    The validity of the metabolism-first approach to the origin of life can be established only through rigorous experimental demonstration under conditions that realistically simulate those of early Earth.

  2. Without enzymes, the rates of the chemical reactions among small molecules in chemical cycles and networks would be too slow to sustain living systems. The proto-metabolic pathways of metabolism-first scenarios require some sort of chemically assisted acceleration.

    Mineral surfaces, to date, are the only reasonable candidates for prebiotic catalysts. While mineral surfaces can catalyze specific reactions, it is unrealistic to think that a mineral will catalyze the range of chemical reactions required for cycles or chemical networks to operate. If a number of different types of mineral surfaces are evoked to increase the catalytic range, it creates an additional problem; namely, the need to efficiently transport “metabolites” from mineral site to mineral site. Under this scenario, it is difficult to envision how a chemical cycle could be maintained and evolve into a metabolic system contained within a protocell. In Orgel’s words, metabolism-first scenarios require an “appeal to magic,” a “series of remarkable coincidences,” a “near miracle.”

  3. Metabolism-first scenarios suffer from the chemical stability-instability paradox. Chemical compounds have to be reactive enough to take part in proto-metabolic cycles and networks. But this reactivity makes them susceptible to breakdown and decomposition. This susceptibility makes the chemical cycles and networks inherently unstable, frustrating all metabolism-first scenarios. On the other hand, chemical compounds stable enough to reasonably withstand degradation cannot enter into chemical cylces and networks because they are not chemically reactive enough.

  4. It is difficult to conceive how information-rich self-replicating molecules could emerge from a proto-metabolic system. It has to be the other way around. In fact, chemist Andy Pross has argued that life’s origin must be replicator-first, not metabolism-first for kinetics reasons.

One final point. Origin-of-life investigators Antonio Lazcano and Stanley L. Miller have identified another problem with metabolism-first scenarios, particularly for those that assert that protometabolic systems resemble the contemporary metabolism found in cells. Lazcano and Miller correctly point out that postulated prebiotic routes for key biomolecules dramatically differ from metabolic pathways that make the same compounds.

Even though on paper metabolism-first scenarios seem plausible, a thorough chemical analysis of these models exposes fundamental and intractable flaws. Metabolism-first scenarios are not viable pathways to life.

No Good Options for the Origin of Life

As I discussed last week, there are inherent problems for replicator-first scenarios. The same is true for metabolism-first scenarios. There are simply no chemical routes from a prebiotic soup to life. The only two options, replicator-first and metabolism-first, fail.

One might observe that the road to a naturalistic origin of life leads to a fork. The hall-of-fame catcher Yogi Berra is reputed to have said, “When you come to a fork in the road take it.” For origin-of-life researchers the fork in the road leads to a dead end.

For a detailed discussion of problems with evolutionary models for the origin of life, see the book I wrote with Hugh Ross, Origins of Life: Biblical and Evolutionary Models Face Off.

Part 1 | Part 2