It looks like a great start Gary. Consider adding to it with commentary about how cells came to be in the first place. One who ponders these issues must come away with the notion that there, at the very least, MAY be a God behind all of what we see. To you and me it is already obvious. What I offer below is far too detailed (and lengthy) for your purpose, but you will get the point. It is arguably the most consequential question facing biology today. Living things are made up of lifeless chemicals, and everything they do is consistent with the laws of physics and chemistry. But nothing in those laws leads one to suspect a universe that harbors life. Yet it does. The history of life unfolds over a time span so vast it boggles the mind. If 1 millimeter were equal to a year, a 3,300 mile flight from Miami to Seattle can put it into perspective. Life first appears over Tennessee, bacterial cells over Kansas and eukaryotes (us, plants and fungi) over Nebraska. The Cambrian explosion occurs over Montana, and mammals first appear near Spokane, WA (smallish mouse-like creatures). The first hominid rises up on his 2 legs less than 2 miles from Seattle and anatomically modern humans only in the last one-tenth of a mile, the last city block.
I recently related the perspective above on a forum, relating a) the enormity of the time period of earth’s existence to the evolution of species. But most importantly of all, b) I related the enormity of the work being put into attempting to understand the origins of life and how exciting that is. None of us have ever imagined the details of the complexity of what is within a single cell. Medical school did not do this topic justice, glossing over any details or conjecture. My thoughts have been met with several reactions, on this forum and elsewhere: 1) One person thought it irrelevant, that all of science was incorrect about evolution. 2) A second person thought the topic not to be of much interest, and that the unknowns only exist because we haven’t studied it long enough, and when we do all the answers will be apparent…thus why worry about it now? He was rather dismissive of even studying the topic. 3) The third person thinks that the scientists are all idiots who think that they “know it all” and they are “always changing their minds anyway”. He thinks scientists have “tunnel vision” ignoring many possibilities. When a scientist says that “in today’s world, membranes never arise de novo” he hears them saying that they never could have arisen de novo, rather than that “they all continue to study all possibilities”. As they see it, the struggle is to merge evolving facts, with logic and science, such that they conform to both current and imaginable life in all possible universes.
There are two universal constituents of cells and they never form de novo. Neither chromosomes nor membranes can do that. Something MUST precede both. A DNA template is required to make another DNA. And membrane growth requires information from preexisting membranes. DNA serves no function other than as a repository of information. Whatever cells do is done by proteins. That is the given.
Every cell originates by division from a pre-existing cell. We refer to the evolution of life without often pondering the specifics of the living cell, much less of a complex animal form. Take an E. coli bacteria. In 20 minutes, this cell, only 2/1000 of a millimeter long, can produce 2 where there was only 1 before. In that time, it produced 2,000,000 protein molecules of 4,000 kinds, 22,000,000 lipid molecules of 60 varieties, and duplicated a double stranded DNA helix of 4.6 million nucleotide pairs that, if uncoiled, would stretch 800 times its length. This represents the 4,200 genes that dictate all aspects of biological structure and function. It also duplicates the cell wall of 2,000,000 repeating units that encases the whole cell. But these membranes surrounding the cell, the nucleus, and the organelles within (Golgi, endoplasmic reticulum, mitochondria, plastids, etc), are not coded to a 3-D form by the genome alone…their construction is one of our greatest mysteries. To quote the premise succinctly: "Protein sequences are encoded in those of DNA, and proteins can only be produced with the help of the machinery of transcription and translation. But all this apparatus consists of proteins and relies on protein enzymes. How, then, could genes have been made or expressed before there were proteins? How could proteins have been produced in the absence of genes to specify them?
LUCA: It is an important corollary that all living cells are members of a single extended family that ultimately share a common ancestry (LUCA, or the last universal common ancestor). A LUCA and evolution is fundamental in BioLogos. And cellular evolution is a special province, acting only upon entities endowed with the capacity for multiplication, heredity, and variation. And cells take us outside Darwinian thought that they must harness energy, maintain integrity and reproduce their own kind long before they diversify into major cell types and body forms that dominate the world today. Traces of this, at the cellular level, have been erased, but we can identify certain landmarks to study the questions of how it occurred. (By genome studies, viruses are NOT descended from LUCA, by the way). But all cellular life shares certain genes, e.g. genes for ribosomal RNA, but there are no genes universally shared by viruses.
So all of science now views cellular organization as fundamental to life. Nothing to date disputes this fact. The genesis of this is under intense study worldwide. We know that cells do not assemble themselves from preformed parts, nor could they have done that in the past. To think about this, one can take it in steps: 1) Who/what was the putative ancestor of all life 2) how did the generation and utilization of energy begin 3) what are the origins of molecular machinery and structural organization of cells 4) how did eukaryotic cells (plants/animals/fungi) came to be 5) did endosymbionts transform into cell organelles? 6) what we have learned from the fossil record and finally 7) finding clues to the inception of entities that possessed the qualities we now call life.
We do now know for certain that there is more to heritability than vertical transfer by DNA. There is lateral transfer from one set of nucleotides to another set in primitive single cells. We can think of verticals as responsible for the specificity, integration and complexity of cellular life. The lateral accounts for the acquisition of novel traits and are in the distant past, but relics can still be made out. Scientists now agree that LUCA had ~353 or as many as 600 genes and the basic mechanisms of transcription (DNA instruction to mRNA) and translation (mRNA to protein molecular construction) were in place. So a lot had to occur before the first single living cell could exist.
Genes can be informational (relating to DNA splicing, coding, selection, etc) or operational (manufacture proteins as enzymes for processes). Lab experiments have not yet found a theoretical method to simultaneously coordinate both the instruction set (DNA) and the enzymes necessary for the processes to both appear at the same time. We can’t have RNA polymerase e.g. without the instruction (DNA), but we can’t have the DNA without the RNA polymerase.
Energy: So much work is being done to decipher the possibilities of producing energy that reading about it feels like a physics course. We consider ATP to be the universal coin of biological energy today. But how did this process come about? In medical school we only studied it at the “substrate-level” or reactions that produce ATP as an integral part of a reaction, turning ADP into ATP in glycolysis. But they now think that the bulk of the world’s ATP came from a current of protons across a membrane to couple an energy source to a specialized enzyme, ATP synthase, to generate ATP. To date, no system compatible with the laws of physics allow this, however. In addition, there must be a membrane to separate a cytoplasm from the environment and there has been no theory yet to satisfy the creation of that membrane. Eukaryotes rely on 2 ways, the degradation of organic matter and the direct capture of light.
Cells and their parts: The most concise definition of life is that it makes itself. All living things make themselves. The machinery to do this boggles the mind. We know what is needed: genes, enzymes/proteins, transport systems, scaffolding, ribosomes, membranes…but we do not know how they came to be. The cell needs “devices”, called organelles, that confer benefits on the organism as a whole, and natural selection confers benefits upon the cell (or organism) as a collective, not just on the constituent part. Take an ancestor of ours, the bacterium and its flagellum. It is made up of 50 interlocking parts, each of which is essential to the function of the whole. A dilemma is seen as we try to visualize them occurring by sequential, small, random steps guided by natural selection since only the complete ‘device’ works. So the concept of an ‘endosymbiont’ gives us a clue, since perhaps the completed device was transplanted intact into the bacteria’s genome at one time. Then the collective has a natural advantage and propagates that forward.
Many scientists say that the most spectacular example of the long-term perpetuation of structure is the persistence of biological membranes. These surround every organelle and the cell itself and have existed for hundreds of millions of years. So membrane heredity is a field in and of itself…yet another mystery being explored. Just as every cell comes from a cell, so does every membrane come from a membrane. This principle rests not on proof positive but on the absence of any known exception.
Emergence of Eukaryotes: about 1 billion years ago, cells appeared with true nuclei bounded by a nuclear membrane with chromosomes that divide by mitosis. They had a cyto-skeleton, discrete organelles each with their own membranes and had motility. Only with the eukaryotes did we integrate multicellular creatures that bear embryos and can think/reason (and listen to music). So just as we have a LUCA, we must have a LECA (last eukaryotic common ancestor). To date, no one has put together a satisfying account of the origin of this pattern which now has a 40 year history of intense study. As one scientist puts it…“it seems that the more we learn, the less we understand”. The cytoplasmic space is integrated by an intricate cytoskeleton meshwork of fibers which track cargo through and orchestrate the “courtly ballet of mitosis”. This still must be accounted for but remains opaque, but some of the organelles seem to have been acquired from endosymbionts (mitochondria, plastids and peroxisomes) but others clearly not and are the focus of most of the studies today. The “signature proteins” are those of the cytoskeleton and endomembrane system, nuclear membrane pores, nucleoli, spliceosomes and others. Investigators can find no genomic pathway that would fit into the “tree of life”, but selective benefits were certainly there for each of them. As one Nobel Laureate says: “When all is said and done (and there has been plenty of both), the genesis of eukaryotic cell organization remains as enigmatic as the provenance of its genes.”
The chemical and biological pathways for photosynthesis deserve some time and the book covers this in a terrific way. We know for certain that before us eukaryotes, the prokaryote cyanobacteria were the first to use pigments to produce O2. They are responsible for the Great Oxidation Event setting the stage for us ~2 Bya. And it seems that this process was invented only one time, passed down sequentially as necessary.
Reading the Rocks: fossil evidence for bacteria has been evasive, but in 1954 evidence was found north of Lake Superior and everything changed. Now there is hope to find the origin of eukaryotic cells, a conundrum second only to the origin of life itself. There is a reason that we get excited about the possibility of O2 on another planet…it is because O2 makes such a good oxidizing agent to produce the necessary energy for life. Physics has yet to find a better agent that meets the criteria we think are necessary for a suitable cycle that uses resources available.
In conclusion, chemists have pursued life’s origins more than biologists have, under the premise that once the molecular building blocks are on hand, organization will take care of itself. That is most certainly incorrect. Modern cells do not assemble themselves from preformed constituents, and they could not have in the past…physical laws and chemistry have not changed. As the scientific community says: “How this might have come about remains one of the deep mysteries of biology”. The holy grail of prebiotic synthesis is the production of a linear macromolecule capable of replicating its own sequence. But so far, efforts to generate such a molecule abiotically have not been successful. An original “RNA world” is most likely. to fill the gap between molecules and cells and the book delves into this in great detail. I would strongly suggest that everyone consider getting the book. Every scientist concludes one of 2 narratives: 1) Standard Model of 3 evolutionary stems, domanis, that separate early in the history of life into Bacteria, Archaea and Eukarya. Or 2) Only two empires, Bacteria and Eukarya with archaebacteria a relatively recent subdomain. Details and persuasive arguments are advanced for both and nothing surfaces that allows falsification of either. And the author ends with a deep and heavy discussion of the philosophical implications of life and evolution. It is very thoughtful. I close with his closing:
For what it’s worth, I suspect that, at the beginning of life, we still know little and understand less. We are acquainted with but a single kind of life, a sample too small to warrant firm conclusions about the nature and genesis of this astonishing phenomenon. What we have learned about life in the cosmos comes from one tiny nook in the vastness of the universe, granting us little warrant for dogmatic pronouncements about what is and is not possible. The beginning of wisdom is to stay tuned, keep listening, relish uncertainty and never let go of the sense of wonder that drew most of us into science in the first place.
In other words, those who discount this topic do so simultaneously as they reveal their lack of wisdom.
Much of this missive comes from 'In Search of Cell History: The Evolution of Life’s Building Blocks" by Franklin M. Harold. I have made the following narrative using (mostly) that resource, but also other recent books such as 13.8 (John Gribbs), Periodic Tales (Hugh Aldersey), Signature in the Cell (Stephen Meyer) and Junk DNA by Nessa Carey.
