Hundreds of huge, bacteria-killing viruses have been newly discovered lurking in all kinds of environments, including our guts. Their massive genomes code for many proteins not found in smaller viruses, including CRISPR systems used to attack both their bacterial hosts and rival viruses.

The massive viruses have long gone unnoticed because the standard methods used to look for bacteria-killing viruses, or bacteriophages, literally filter them out. Instead, a team has found them by looking at all the DNA present in a variety of samples, an approach known as metagenomics.

The researchers then pieced together the genomes of the huge phages using a method developed by team leader Jill Banfield at the University of California, Berkeley.

Bacteriophages are the most common entities on Earth. There can be many millions in a drop of seawater. Almost all known phages have genomes tens of thousands of DNA letters long at most. Larger ones were thought to be very rare. But earlier this year, Banfield's team reported finding more than a dozen phages with genomes up to 540,000 DNA letters long in the guts of humans and animals.

In his 2014 book, Our Mathematical Universe, physicist Max Tegmark boldly claims that "protons, atoms, molecules, cells and stars" are all redundant "baggage." Only the mathematical apparatus used to describe the behavior of matter is supposedly real, not matter itself. For Tegmark, the universe is a "set of abstract entities with relations between them," which "can be described in a baggage-independent way" - i.e., without matter. He attributes existence solely to descriptions, while incongruously denying the very thing that is described in the first place. Matter is done away with and only information itself is taken to be ultimately real.


This abstract notion, called information realism is philosophical in character, but it has been associated with physics from its very inception. Most famously, information realism is a popular philosophical underpinning for digital physics. The motivation for this association is not hard to fathom.

Indeed, according to the Greek atomists, if we kept on dividing things into ever-smaller bits, at the end there would remain solid, indivisible particles called atoms, imagined to be so concrete as to have even particular shapes. Yet, as our understanding of physics progressed, we've realized that atoms themselves can be further divided into smaller bits, and those into yet smaller ones, and so on, until what is left lacks shape and solidity altogether. At the bottom of the chain of physical reduction there are only elusive, phantasmal entities we label as "energy" and "fields" - abstract conceptual tools for describing nature, which themselves seem to lack any real, concrete essence.

This is the third in a series of posts responding to the extended critique of Darwin Devolves by Richard Lenski at his blog, Telliamed Revisited. Professor Lenski is perhaps the most qualified scientist in the world to analyze the arguments of my book. He is the Hannah Distinguished Professor of Microbial Ecology at Michigan State University, a MacArthur ("Genius Award") Fellow, and a member of the National Academy of Sciences with hundreds of publications. He also has a strong interest in the history and philosophy of science. His own laboratory evolution work is a central focus of the book. I am very grateful to Professor Lenski for taking time to assess Darwin Devolves. His comments will allow interested readers to quickly gauge the relative strength of arguments against the book's thesis.

Unintended Consequences

I have already addressed several of the issues that Lenski has raised at his blog in his third post on Darwin Devolves, "Is the LTEE Breaking Bad?," in my responses (here, here, and here) to the review by my Lehigh colleagues, because they cited his work frequently. Nonetheless, repetition is a fine teaching tool. So here I will again speak to those issues and also address a few others.

In "Is the LTEE Breaking Bad?" Lenski agrees that the beneficial mutations seen in his Long Term Evolution Experiment are overwhelmingly degradative or loss-of-function ones. Even so, that does not concern him because "the LTEE represents an ideal system in which to observe degradative evolution." Beneficial degradative changes are only to be expected there, it seems.

The LTEE was designed (intelligently, in my opinion!) to be extremely simple in order to address some basic questions about the dynamics and repeatability of evolution, while minimizing complications. It was not intended to mimic the complexities of nature, nor was it meant to be a test-bed for the evolution of new functions. The environment in which the bacteria grow is extremely simple. ...

Indeed, the LTEE environment is so extremely simple that one might reasonably expect the bacteria would evolve by breaking many existing functions. That is because the cells could, without consequence, lose their abilities to exploit resources not present in the flasks, lose their defenses against absent predators and competitors, and lose their capacities to withstand no-longer-relevant extreme temperatures, bile salts, antibiotics, and more. [Emphasis in the original.]

In other words, there are many tools in the robust E. coli genomic toolbox that wouldn't be needed in the Michigan State lab. It could lose them without immediate consequence. In fact, there may even be some benefit to losing them, either by simply saving the energy of making them, or by diverting resources to other pathways that are more heavily used in the lab environment.

For the first time, scientists have engineered the complex biological process of translation into a designer organelle in a living mammalian cell. Research by the Lemke group at the European Molecular Biology Laboratory (EMBL) -- in collaboration with JGU Mainz and IMB Mainz -- used this technique to create a membraneless organelle that can build proteins from natural and synthetic amino acids carrying new functionality. Their results -- published in Science on 29 March -- allow scientist to study, tailor, and control cellular function in more detail.

During evolution, the development of new organelles allows cells and organisms to become more complex, due to the ability to sort cellular processes into specific hotspots. "Our tool can be used to engineer translation, but potentially also other cellular processes like transcription and post-translational modifications. This might even allow us to engineer new types of organelles that extend the functional repertoire of natural complex living systems," explains Christopher Reinkemeier, PhD student at EMBL and JGU Mainz and co-first author of the paper. "We could for example incorporate fluorescent building blocks that allow a glimpse inside the cell using imaging methods."

"The organelle can make proteins by using synthetic non-canonical amino acids. Currently we know of more than 300 different non-canonical amino acids -- compared to 20 which are naturally occurring. We are no longer restricted to the latter ones," says co-first author Gemma Estrada Girona. "The novelty we introduce is the ability to use these in a confined space, the organelle,, which minimises the effects on the host."

Given enough time, even a tidy room will get messy. Clothes, books and papers will leave their ordered state and scatter across the floor. Annoyingly, this tendency toward untidiness reflects a law of nature: Disorder tends to grow.

If, for example, you cut open a pressurized scuba tank, the air molecules inside will spew out and spread throughout the room. Place an ice cube in hot water and the water molecules frozen in the ordered, crystalline lattice will break their bonds and disperse. In mixing and spreading, a system strives toward equilibrium with its environment, a process called thermalization.

It's common and intuitive, and precisely what a team of physicists expected to see when they lined up 51 rubidium atoms in a row, holding them in place with lasers. The atoms started in an orderly pattern, alternating between the lowest-energy "ground" state and an excited energy state. The researchers assumed the system would quickly thermalize: The pattern of ground and excited states would settle almost immediately into a jumbled sequence.

And at first, the pattern did jumble. But then, shockingly, it reverted to the original alternating sequence. After some more mixing, it returned yet again to that initial configuration. Back and forth it went, oscillating a few times in under a microsecond - long after it should have thermalized.

It was as if you dropped an ice cube in hot water and it didn't just melt away, said Mikhail Lukin, a physicist at Harvard University and a leader of the group. "What you see is the ice melts and crystallizes, melts and crystallizes," he said. "It's something really unusual."

Physicists have dubbed this bizarre behavior "quantum many-body scarring." As if scarred, the atoms seem to bear an imprint of the past that draws them back to their original configuration over and over again.

Researchers have bio-engineered blood vessels that when implanted into a patient are quickly colonised by native cells and become self-sustaining.

A team led by Robert Kirkton of US-based regenerative medical tech company Humacyte Inc created biodegradable scaffolds in the form of blood vessels and then seeded them human vascular cells before incubating them in a bioreactor for eight weeks.

After the incubation, Kirkton and his colleagues removed all the cellular material, leaving behind what they term human acellular vessels (HAVs).

In a four year phase II clinical trial, the HAVs were implanted into 60 patients with end-stage kidney failure, where they served as entry ports for hemodialysis treatments - an approach which requires access to healthy blood vessels.

Recently two of my Lehigh University Department of Biological Sciences colleagues published a seven-page critical review of Darwin Devolves in the journal Evolution. As I'll show below, it pretty much completely misses the mark. Nonetheless, it is a good illustration of how sincere-yet-perplexed professional evolutionary biologists view the data, as well as how they see opposition to their views, and so it is a possible opening to mutual understanding. This is the third of a three-part reply. It continues directly from Part 2. See here for Part 1.

Of Course Proteins Are Machines

A basic difference between the views of Greg Lang and Amber Rice and my own concerns the nature of the molecular foundation of life. They object that I consider many biochemical systems to be actual machines. They quote a line from Darwin Devolves stating that protein systems are "literal machines - molecular trucks, pumps, scanners, and more." They write disapprovingly that the book claims "rod cells are fiber optic cables ... The planthopper's hind legs are a 'large, in your face, interacting gear system.'" They do concede that I didn't make up those claims about the machine-like nature of the systems out of whole cloth: "Most of the analogies in Darwin Devolves are not Behe's creation - he has done well to scour press coverage and the scientific literature for relatable metaphors; and he is generous with their use." Nonetheless, they say, "reality remains: proteins are not machines, a flagellum is not an outboard motor."

On this point they are simply wrong. "Molecular machine" is no metaphor; it is an accurate description. Unless Lang and Rice are arguing obliquely for some sort of vitalism - where the matter of life is somehow different from nonliving matter - then of course proteins and systems such as the bacterial flagellum are machinery. What else could they be? Although they aren't made of metal or plastic like our everyday tools, protein systems consist of atoms of carbon, oxygen, nitrogen, and so on - the same kinds of atoms as are found in inorganic matter, nothing special.

Recently two of my Lehigh University Department of Biological Sciences colleagues published a seven-page critical review of Darwin Devolves in the journal Evolution. As I'll show below, it pretty much completely misses the mark. Nonetheless, it is a good illustration of how sincere-yet-perplexed professional evolutionary biologists view the data, as well as how they see opposition to their views, and so it is a possible opening to mutual understanding. This is the second of a three-part reply. It continues directly from Part 1.

A Limited Accounting of Degradation

Greg Lang and Amber Rice cite a number of articles to show that loss-of-function mutations are just a small minority of those found in studies of organisms.

However, the truth is that loss of function mutations account for only a small fraction of natural genetic variation. In humans only ∼3.5% of exonic and splice site variants (57,137 out of 1,639,223) are putatively loss of function, and a survey of 42 yeast strains found that only 242 of the nearly 6000 genes contain putative loss of function variants. Compared to the vast majority of natural genetic variants, loss of function variants have a much lower allele frequency distribution.

Yet those three studies they cite all search only for mutations that are pretty much guaranteed to totally kill a gene or protein. For example, one paper says:

We adopted a definition for LoF variants expected to correlate with complete loss of function of the affected transcripts: stop codon-introducing (nonsense) or splice site-disrupting single-nucleotide variants (SNVs), insertion/deletion (indel) variants predicted to disrupt a transcript's reading frame, or larger deletions ...

That's akin to counting only burnt-out shells of wrecked cars as examples of accidents that degrade an auto, while ignoring fender benders, flat tires, and so on. There are many more mutations that would not be picked up by the researchers' methods that nonetheless would be expected to seriously degrade or even destroy the function of a protein. Since the rates leading to the kinds of mutations in the cited papers are likely to be at least ten-fold lower than general point mutations in the gene (which, again, the study passed over) there may be many more genes - perhaps five- to ten-fold more (about a quarter to a half of mutated genes) - that have been degraded or even functionally destroyed. Further research is needed to say for sure. (I know which way I'll bet.) The remaining fraction of mutated genes in the population is likely to consist mostly of selectively neutral changes, neither helping nor hurting the organism, and not contributing anything in themselves to the fitness of the species.

Similar to the dozens of Sherpas that guide hikers up treacherous Himalayan mountains to reach a summit, the nervous system relies on elaborate timing and location of guidance cues for neuronal axons-threadlike projections-to successfully reach their destinations in the body. Now, Salk Institute researchers discover how neurons navigate a tricky cellular environment by listening for directions, while simultaneously filtering out inappropriate instructions to avoid getting lost. The findings appeared in Neuron on March 19, 2019.

"There are 100 trillion connections in the nervous system governed by 20,000 genes, of which roughly 10 gene families are known to be involved in controlling axon guidance. We wanted to understand the clever genetic systems nature has employed to wire the most complicated biological machine in the universe," says Salk Professor Samuel Pfaff, senior author and a Howard Hughes Medical Institute investigator. "Thus, we set out to examine how motor neurons find their connections with muscles in the body, which is critical for our brain to relay information to our muscles to allow for movement."

The brain controls hundreds of different muscles to allow for precise movement. During development, motor neurons in the spinal cord extend their axons outside of the central nervous system to connect with muscle cells in the body. Every motor neuron relies on a set of genes to ensure the axon grows correctly to the muscle.

Clumps of harmful proteins that interfere with brain functions have been partially cleared in mice using nothing but light and sound.

Research led by MIT has found strobe lights and a low pitched buzz can be used to recreate brain waves lost in the disease, which in turn remove plaque and improve cognitive function in mice engineered to display Alzheimer's-like behaviour.

It's a little like using light and sound to trigger their own brain waves to help fight the disease.