What Makes a Protein Truly Functional? Viability, Usefulness, and Preservation in Debate

Before claiming that functionality already implies viability, usefulness, and preservation, we should ask: what exactly makes a protein useful within a living system? How do we know it will be preserved across generations? And most importantly, what alternative mechanisms could resolve this paradox before natural selection can act?

The Complexity of Isolated Functionality

Proponents of the idea that functionality includes viability, usefulness, and preservation certainly seek to simplify explanatory models—which is understandable from the perspective of scientific parsimony. However, experimental data suggests that biological reality is more complex.

Biochemist Douglas Axe (2004) demonstrated that only 1 in 10⁶⁴ β-lactamase sequences maintains catalytic function. This alone shows that functionality, by itself, is extremely rare.

Even naturalism proponents like Doolittle (2013) openly admit: "the origin of the coagulation system remains challengingly unexplained." This admission is significant coming from a researcher who dedicated decades to the evolutionary study of this system.

Furthermore, catalytic function does not guarantee biological viability. Studies like Lynch (2007) show that functional proteins can be unviable in cellular contexts—whether due to toxicity or energy cost. That is, a protein may function in the laboratory but be harmful or useless within a living cell.

Adami et al. (2000) reinforce this point: even functional proteins may not be "useful" if not integrated into complex systems. Isolated function is not enough—context, compatibility, and molecular cooperation are needed.

The Conceptual Confusion About Functionality

This criticism seems to assume a conceptual equivalence that experimental data challenges: the idea that functionality automatically includes viability, usefulness, and preservation. But as a scientific community, we need to confront these challenging data with honesty.

In practice, proteins can be functional in vitro (in the laboratory) but not in vivo (in living organisms). Tokuriki & Tawfik (2009) show that mutations that confer function can destabilize the protein, making it unviable.

What evidence could demonstrate that viability is truly intrinsic to functionality? How would we test this hypothesis rigorously?

Quantifying Biological Filters

Let's explore together why this issue is more complex than it initially appears.

P(function) = 10⁻⁶⁴ (Axe, 2004)
P(viability | function) ≈ 10⁻² (Lynch, 2007)
P(usefulness | viability) ≈ 10⁻¹ (Adami, 2000)
P(preservation | usefulness) ≈ 10⁻¹ (Kimura, 1983)

Multiplying:

P(total) = 10⁻⁶⁴ × 10⁻² × 10⁻¹ × 10⁻¹ = 10⁻⁶⁸

Durrett & Schmidt (2008) mathematically demonstrate that even for just two specific sequential mutations, the required waiting time exceeds the cosmic time available in populations of realistic size (Nₑ ≤ 10⁹). For k = 2 mutations in regulatory sequences, the average waiting time is 10⁸ years in mammals—significantly longer than available evolutionary time.

Why a Protein Is Not a System

Even if a protein meets all these criteria, it is still not sufficient. Biological systems require multiple interdependent proteins.

Classic example: the blood coagulation cascade, described by Behe (1996), involves 12 proteins that must function together. An isolated protein, no matter how functional, does not explain the system.

The anomaly is even more pronounced when its own proponents admit the lack of explanations. Doolittle (2013), after 40 years of research, concludes that no satisfactory evolutionary model exists for the origin of the coagulation cascade.

Behe (2007) documents the observable limits of evolution through studies of malaria and HIV. His data shows that even under intense selective pressure and huge populations, evolution produces only marginal changes (e.g., drug resistance through loss of function), never originating new irreducibly complex systems. The complexity barrier remains insurmountable for undirected mechanisms.

Conclusion and Invitation to Dialogue

The random generation of a functional protein is not enough. It must be:

Viable: non-toxic, energetically compatible
Useful: integrated into an adaptive system
Preservable: capable of resisting genetic drift and deleterious mutations

Each of these steps represents a rigorous biological filter—and ignoring them is ignoring the molecular reality of life.

We recognize that these questions are complex and challenging for all models. We invite colleagues from all perspectives to a dialogue based on the data presented here.

And we leave one final question open for debate:

If we recognize that these filters exist and that natural selection only acts after viability, what alternative mechanisms could resolve this paradox before natural selection can act?