Molecular Basis of Vision
GPCRs at the cellular level (Fig. 1 Credit: Creative BioMart)
In John’s Gospel, the entirety of Chapter 9 is devoted to a story of Jesus restoring sight to a man who was blind from birth. Jesus spit on the ground, made a mud with his saliva, put the mud on the blind man’s eyes, and told him to wash off the mud in the pool of Siloam. The man followed Jesus’ instructions and received his sight.
I’m reminded of a similar story – the first time I witnessed a real miracle - that I experienced in 1970 while attending a Katheryn Kuhlman “miracle service” at First Presbyterian Church in Pittsburgh, PA. I arrived at the church in the early morning, hours before the service. While outside, I met a grandmother, mother, and seven-year-old boy from Toronto, Canada. They brought the boy, totally deaf, born without ear drums, in hopes that God might give him hearing. About half-way through the service, with thousands in attendance, Ms. Kuhlman paused, pointed to a section of the balcony, and called to the stage the boy and his family. It was the boy I had met earlier that morning. After putting the lad through a series of maneuvers to help demonstrate he could hear, it became clear that Jesus had created a new set of ear drums in the boy – I witnessed a miracle!
If we believe that miracles can happen, our human nature tends to categorize them into degrees of difficulty. For example, raising someone from the dead would be more of a challenge to God than restoring sight, which would be more difficult than answering some of our simple prayers (for whatever). With that in mind, let’s take another look at the miracle of vision.
I just read an article in the September 30, 2019 issue of ScienceDaily. “Researchers have solved the three-dimensional structure of a protein complex involved in vertebrate vision at atomic resolution, a finding that has broad implications for our understanding of biological signaling processes and the design of over a third of the drugs on the market today.” Here’s what it looks like (in schematic): it starts with a neurotransmitter, also called a ligand, from the environment outside of the cell. The ligand could be a photon of light or an odor or a hormone or an opiate or a peptide*. As soon as the GPCR receives the ligand, it activates a G-protein, which in turn activates a whole chain of events inside the cell.
GPCR with G-protein (Fig. 2 Credit: WordPress)
Inside the retinas of our eyes are photoreceptor cells called rods and cones (color sensitivity). Figure 2 is a schematic of the outer cell membrane of a typical rod or cone cell. The neurotransmitter-ligand (red ball), is a photon (particle of light) received by the eye’s retina from outside the cell wall. The green is a GPCR [G-protein-coupled receptor (“G” stands for guanine nucleotide-binding protein)]. A GPCR specific to light, rhodopsin, is embedded in the cell membrane of a typical rod cell. Rhodopsin can detect the signal from just one sub-atomic photon of light, which, once received, activates a G-protein (purple) inside the cell called transducin, which can amplify the photon by 100,000 times.
Rhodopsin (Fig. 3 Credit: SnipView)
Figure 3 adds more detail. To the right is another version of Figure 2. The left schematic of a rod cell shows the link connecting the GPCR rhodopsin, through the cell body and nucleus. From here the signal passes through a series of specialized cells before arriving at the optic nerve and into the brain, where the signal can be interpreted. Multiply these times 6 million cones and 120 million rods in a single human retina!
Very interesting – so what’s the point?
Did you know that the mechanisms for sight, as described above, have been operational in vertebrates (humans are vertebrates) as far back as the ancient Cambrian Period, some 500 million years ago? This poses real problems for evolutionary scientists for a couple of reasons; there doesn’t appear to have been enough time for evolution to develop such a complex organ as the eye, and very few evolutionary changes to the original eye-design have occurred over a very long 500-million-year span. The eye with its extreme intricacy makes a compelling case for an “irreducible complexity”** argument, and the need for the intervention of an Intelligent Designer.
Medical Breakthrough
Immuno-therapy, gene-therapy – these are some of the familiar terms heard these days in the search for a cure to cancer, or the development of targeted drugs. Ever wonder why the cost of developing a new drug is so high, and why it takes so long to get approved? Imagine you are a biomedical researcher tasked with finding a cure for a specific cancer. There are over 1000 GPCRs in humans that signal 20 different G-proteins, and 20,000 peptide ligands that could activate these GPCRs. The cure for cancer could lie in identifying the specific GPCR - G protein - ligand combination (out of a possible 400 million combinations) that will begin to unlock the answer. Let’s say you find that one-in-400 million (needle in a haystack), next you must decide which of five pathways the activated G-protein might travel. It gets even more complex; the G protein is trimeric, meaning it has three subunits: alpha, beta, and gamma.
Figure 4 (Credit: University of Tampa)
The G proteins then transfer to “scaffolding proteins” which further regulate GPCR signaling (see Figure 4). One of the most important pathways leads directly into the cell nucleus where the genetic activity takes place, e.g., RNA transcription, and gene expression. This leads directly to biological responses, such as proliferation, cell survival, and cancer. Many cancers are the result of a genetic flaw. Researchers can spend their whole career studying one GPCR signaling system with the hope to gain insights into designing drugs that specifically regulate GPCR signaling.
Just imagine - the average human being is made up of roughly 37 trillion cells, and the process described in this blog is constantly taking place in each cell. Yet, somehow all that information is making its way to the brain where it can be processed in real time. To me, that’s a testament to the elegance or fingerprint that only our Creator could design! Life is truly miraculous.
*A peptide is a molecule composed of short-chained amino acids linked by peptide (amine) bonds. When peptides are coupled, they form larger, more complex molecules called proteins.
**Irreducible Complexity (IC) involves the idea that certain biological systems cannot evolve by successive small modifications to pre-existing functional systems through natural selection. Examples of IC would be “molecular motors”, or an analogy called the “watchmaker argument”, whereby a design implies a designer.