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Free Will
Mental Causation
James Symposium
Ladislav Kovàč

Ladislav Kovàč is a professor of biochemistry and cognitive biologist at the Biocenter of Comenius University in Bratislava, Slovakia. He founded the Laboratory of Comparative and Functional Genomics of Eukaryotic Organelles.

He is a strong advocate for seeing biological systems and subsystems as exhibiting cognition, even in some of the smallest biological structures. Jacques Monod suggested that even proteins have a kind of cognition in their ability to distinguish between substrates and ligands. Ligands that bind to cell receptors, such as activators, inhibitors, and neurotransmitters, can be considered as signaling the cell.

When the receptor undergoes a conformational change in response to the signal, we can say that the receptor "knows what to do" with the signal, and that the signal therefore has "meaning." Various receptors turn cells into "biological information-processing systems." They make the cells (and even sub-cellular organelles) into teleonomic (purposeful) agents. As Monod's colleague, François Jacob, put it, "the purpose of every cell is to become two cells."

Kovàč describes the process of recognition by molecules and their subsequent purposeful actions:

molecular recognition by a protein molecule is only part of the story. Recognition is followed by an action. A ligand is a signal. In contrast to standard chemical interactions, binding energy is not fully dissipated as heat, but is used partly for molecular work — a specific pre-programmed change in the conformation of the protein. In this way, the signal is transmitted from one site on the protein to another. The transmission takes place in four-dimensional space, as it involves time as a coordinate, and this process gives biochemistry its vectoriality. The exploitation of binding energy was originally recognized in enzymatic catalysis, in which a portion of the binding energy acts to lower the activation energy of a reaction, but it can be expanded to explain the work of translocators, receptors and transcription factors.

By receiving and transmitting signals, proteins execute a complete working cycle in an ‘all or nothing’ fashion. It is appropriate to regard most protein molecules as molecular engines. Hence, molecular cognition consists of molecular sensation — which has two inseparable aspects, recognition and signifaction — and molecular action. As Monod pointed out, by binding two or more ligands, some proteins can bring them together not on thermodynamic, but exclusively on logical, grounds — the principle of gratuity. By selective binding, proteins also associate with each other to form purposeful protein networks. In addition, owing to their structural asymmetry, protein molecules can use thermal energy from the environment to perform work as Brownian ratchets. It is essential to acknowledge that all the activities of a protein reside in its structure, which is built in by evolution. In terms of Shannon’s communication theory, the exploratory behaviour of a protein molecule — its constant change between sub-states — is a manifestation of its information entropy. The appropriate ligand triggers pre-programmed responses; the whole process is nothing more than a one-bit information transaction.

Describing a protein as a cognizing agent would appear to be a blatant example of extreme anthropomorphism, but Kovàč's work is showing how human consciousness (defined as awareness of meaningful signals coming in and appropriate reactions going back out to the environment) may have evolved from the simplest forms of life, indeed from sub-units of life that are not themselves living systems.

The possible "actions" of a protein molecule are encoded in the possible conformations (different "foldings") of the protein. If it had a single conformation, it would be useless. As Shannon showed us, a system communicating information must have multiple "possible" messages. With only a single possibility, no new information could be communicated.

Changes in the conformation require energy with negative entropy. This is provided by the nearly universal energy carrier ATP, which dephosphorylates, giving up one phosphate group to become ADP. As Erwin Schrödinger said in "What Is Life?," life feeds on stream of negative entropy from the sun. We can see the conformational change, and the energy provided by ATP, in the working of the ion channel Na+/K+ (sodium-potassium pump) that moves ions back across the neuron cell membrane to restore the resting potential and prepare the cell for another activation spike.

For Kovàč, the proteins that make up the sodium-potassium pump are "sentient." They are exhibiting purposeful behavior when they change their conformation to allow in one type of ion, then change the conformation again to allow them out on the other side of the membrane.

He says that:

Each of the proteins we encounter in nature is a product of evolution; it has been selected to perform a goal-directed teleonomic function.

For most natural proteins, the function begins with the specific binding of a ligand. But it is not the protein molecule as a rigid structure that selects the appropriate ligand. There are constant structural changes between sub-states, even in the absence of a ligand. When the ligand is present, it binds to one particular sub-state that the protein molecule is able to adopt—it is therefore possible to say that a protein molecule exhibits exploratory ‘behaviour’. This intrinsic goal-directed plasticity of the protein molecule can be dubbed ‘molecular sentience’, and it is this sentience that makes a protein a ‘living’ molecule... Sentience — the capacity to exhibit a variety of potential internal states, which respond to the immediate state of the environment— might therefore constitute the essence of life.

It is this purpose, built into the protein structure, which allows us to call protein–ligand interaction ‘molecular recognition’. Because of this intrinsic teleonomy, a protein gives meaning and significance to its environment—that is, to its ligand. By contrast, nomic interactions of individual atoms and molecules, such as chemical reactions in the inanimate world, with no evolutionary history, are inevitable, deterministic, timeless and do not represent cognition.

The field of cognitive biology was founded by the theoretical and mathematical biologist
Brian Goodwin in the 1970's.

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