On life's machine code.

Is Genome Grammar Just a Figure of Speech?

Evolution News & Views 

Without controversy, everyone knows texts written by human beings are intelligently designed, unless they are ramblings from a maniac. Human language is characterized by syntax (rules of word order) and grammar (rules of spelling, part of speech, case, person, number, voice, tense, mood, etc.). But that's not enough. One can follow the rules and make up nonsense sentences, such as "Banana voices improve inspirational aardvark submarines." For effective communication, language must also make sense. That's semantics: the communication of meaningful ideas.

Does DNA meet these conditions? How proper is it to discuss the DNA code as a language? We should point out that software meets the requirements of language. It, too, has rules of syntax, grammar, and semantics, even though humans do not speak it in conversation. The sender and receiver do not have to be sentient beings; software can drive actions on spacecraft, for example. We must also expand the range of languages beyond the English of this paragraph to include all languages, past and present, used by humans, plus all forms of coded information (including Morse code, sign language, mathematics, and even the rope-knot language of the Incas). Rules can vary widely between languages, but they all have in common the purposeful communication of meaningful information, regardless of the substrate or carrier of the symbols used.

Analogies can enlighten, but they can also mislead. We in intelligent design circles are prone to assume the comparison between DNA and language, but we must beware of drawing the analogy too tightly, even though most scientists unhesitatingly speak of the "genetic code" and the "language of life." Dubious comparisons have been made between brains and computers, as Dr. Michael Egnor has pointed out. Sometimes the differences are more significant than the similarities.

With these caveats in mind, we can examine the analogy between language and genomics. In a Commentary article in the Proceedings of the National Academy of Sciences, Scott Barolo from University of Michigan Medical School refers several times to the grammar and syntax of DNA. He's not trying to prove genes are analogous to language; the comparison just comes naturally as he discusses the roles of enhancers in gene expression.

Every cell's genome contains two main classes of functional DNA. The best understood type of DNA sequence, which was also the first to be discovered, is that which encodesRNA and protein products via the near-universal "genetic code". A more mysterious but equally important class of functional DNA is cis-regulatory sequence, which does not have a physical product but, instead,encodes the conditions under which a particular RNA will be produced.Cis-regulatory DNA sequences are the primary (although not the only) determinant of gene expression: Not only the rate of RNA production but also the timing, spatial patterning, and environmental control of every gene's activity are largely controlled by these DNA sequences, which are usually in the general vicinity of the gene they regulate. These DNA segments (often called enhancers) have no enzymatic activity on their own, but act as scaffolds for large complexes of proteins and RNAs that directly control the activity of a gene's promoter, sometimes over distances of 1 million base pairs or more. Transcription factors (TFs), key protein regulators of gene expression, bind DNA in a sequence-specific manner, which means that the nature of the complex assembled at a given enhancer at a given timedepends on its DNA sequence (cisinformation), in conjunction with the set of TFs present and active in the cell at that time (trans information). The chromatin state of regulatory DNA is also a very important factor, but local chromatin states are alsospecified, indirectly, by DNAsequence, because most chromatin-modifying enzymes are recruited to the genome by sequence-specific factors. [Emphasis added.]

So far, Barolo has only compared DNA to codes where the specific sequence matters. Next, he adds references to grammar and syntax:

In part, the DNA sequence of an enhancer encodes a pattern of gene expression through the combinations of sequence-specific regulators that bind to it (and the non-DNA-binding factors they recruit, in turn). However, cis-regulatory DNA sequences do more than merely determine which combinations of TFs will be recruited to an enhancer. The linear arrangement of binding sites (sometimes called "grammar" or "syntax") can play an important role in controlling enhancer output, especially by setting thresholds for gene activation.

By putting "grammar" and "syntax" in quotes, Barolo is acknowledging similarity but not necessarily identity.

In texts, we don't see alphabet letters swooping down and binding onto existing words or paragraphs to give them more "expression" or regulate what parts are readable. That's one important difference. In software, however, routines can be switched on or off depending on environmental factors. Also, in routing, tags can be attached to packets of information that permit or block their transmission, or determine their destinations. Those tags are very sequence-specific. One wrong character can disrupt function.

Barolo turns his attention to another paper inPNAS by Farley et al., who "investigate how the binding affinity and the spatial arrangement of TF binding sites within enhancers interact toencode precise patterns of gene expression in developing embryos." The scientists are basically trying to learn a foreign language by watching what certain words or paragraphs do. If they see one sequence (a binding site) activated by an enhancer, they might be able to predict other binding sites. The "spatial arrangement" refers to placement of binding sites within the sequence, analogous to word order in text, or to start-stop codes for switches in software routines. The analogy may not be exact, he suggests. We just don't know enough yet.

Taking the rules of syntax into account may provide an essentialsource of information for predicting enhancer outputs. However, theimportance of syntax/grammar for enhancer function is still debated; what has been needed is more experimental data.

While we still don't fully understand the rules of DNA, the assumption of syntax and grammar appears to be a fruitful heuristic. One only has to observe how accurate the DNA software runs!

In their new report, Farley et al. propose an interesting idea: Because current methods of enhancer prediction focus on high-affinity TF binding sites, perhaps they are best at identifying those enhancers that are the least subject to constraints on binding site syntax. If true, this approach would tend to paint a biased picture of the constraints that shape enhancer sequences. Now that a more complete view of the relationship between DNA sequenceand enhancer function is slowly emerging (Fig. 1), future predictive methods may be more effective at computing gene expression patterns from genomic DNA sequences. After all, that is a task that cells perform every day, with astonishing reliability and precision.

Let's take stock of the analogy between genomics and language.

• We know in human language and in software that "astonishing reliability and precision" depend strongly on sequence specificity. Unclear writing reduces information. Sloppy coding crashes or reduces functionality.
• The placement of binding sites, whether on cis (same) or trans (opposite) sides of the DNA double helix, matters. Similar constraints obtain for language and software code: word order matters in most languages.
• TFs must match their binding sites. In languages, subjects and verbs must agree. In codes, arguments for routines must follow the rules for length, character type, and order.
• Barolo's title, "How to tune an enhancer," refers to the ability of binding sites and transcription factors to affect "not only the rate of RNA expression but also the timing, spatial patterning, and environmental control of every gene's activity." One might compare this to keywords in internet searches, tags on social media messages, or prefixes and suffixes in certain languages that affect the meaning.
• DNA can be translated from the DNA code into the protein code. This resembles translators (whether human or machine) that can convert English into Chinese. Both have to share the same language convention.
• DNA uses molecules that symbolize or represent something else. Similarly, languages use symbols whose shapes do not necessarily represent what they mean.

An analogy is more useful the more factors it shares with its referent, and the fewer it doesn't share, especially when the shared factors are the most significant ones. Human language may lack the 3-D shape and activity of DNA "letters" but shares the most important characteristic: reliable communication of information for a functional result. It also shares requirements for specificity and rules of operation. If anything, the comparison is from the lesser to the greater: if human language is designed, how much more the "astonishing reliability and precision" of the genome?

Deconstructing a 'just so' story

Gegenbaur Revisited: Assessing the "Limbs from Gills" Scenario
Michael Denton 

Science Daily announces:

Sonic hedgehog gene provides evidence that our limbs may have evolved from sharks' gills

Latest analysis shows that human limbs share a genetic programme with the gills of cartilaginous fishes such as sharks and skates, providing evidence to support a century-old theory on the origin of limbs that had been widely discounted.

An idea first proposed 138 years ago that limbs evolved from gills, which has been widely discredited due to lack of supporting fossil evidence, may prove correct after all -- and the clue is in a gene named for everyone's favourite blue hedgehog.

Unlike other fishes, cartilaginous fishes such as sharks, skates and rays have a series of skin flaps that protect their gills. These flaps are supported by arches of cartilage, with finger-like appendages called branchial rays attached.

In 1878, influential German anatomist Karl Gegenbaur presented the theory that paired fins and eventually limbs evolved from a structure resembling the gill arch of cartilaginous fishes. However, nothing in the fossil record has ever been discovered to support this.

Now, researchers have reinvestigated Gegenbaur's ideas using the latest genetic techniques on embryos of the little skate -- a fish from the very group that first inspired the controversial theory over a century ago -- and found striking similarities between the genetic mechanism used in the development of its gill arches and those in human limbs.

Scientists say it comes down to a critical gene in limb development called 'Sonic hedgehog', named for the videogame character by a research team at Harvard Medical School.

The intriguing paper in the journal Development is here, and a very lucid description by one of the authors, J. Andrew Gillis, is here.

Gillis and his co-author Brian K. Hall provide evidence showing that in the development of the gill or branchial arches (a paired series of skeletal elements that support the gills and run down either side of the pharynx in fishes) and of the branchial rays (cartilaginous rods that articulate at their base with the gill arches in sharks and rays and protrude laterally from the gill arches), the common toolbox gene sonic hedgehog (Shh) establishes the anterior-posterior axis and the proliferative expansion of branchial endoskeletal progenitor cells. Those are the cells that give rise to the internal support system in vertebrates, composed of bone (in bony fishes and tetrapods) or cartilage (in sharks and rays).

What is the significance of their report? It is that precisely the same gene establishes the anterior-posterior axis in the tetrapod limb (in the human hand this is the axis from the thumb to the little finger) and promotes proliferation of the endosketal progenitor cells. This, as mentioned, supports a notion first proposed more than a century ago by the great German morphologist Carl Gegenbaur. As Gillis and Hall point out in a recent PNAS paper:

Gegenbaur drew parallels between the organization of the gill arch skeleton with that of the paired appendage skeletons of gnathostomes [jawed fishes], homologizing the appendage girdle with the proximal branchial arch, and the endoskeleton of paired fins proper with the distal branchial rays.

On this theory, the fin and limb girdles of vertebrates would be homologous to and derived from gill or branchial arch skeletal elements. Meanwhile the lateral appendages, the fins and limbs themselves, would be homologous to and derived from branchial rays.

In light of Gillis and Hall's research, Gegenbaur might turn out to have been right. However, as with so many other evolutionary transitions, one of the major problems in assessing his "arch to fin" scenario is, as Gillis and Hall confess, the absence of any known intermediates between branchial arches and fins. The gap between a branchial ray and a fish fin is certainly considerable (as is obvious in figure 1 in the Gillis and Hall paper). And the existence of developmental homologies throws no light on the question of how the evolutionary transformations might have come about.

Was it, as Darwin envisaged, via a long series of adaptive intermediates, i.e., imposed by external constraints? Or did it occur via a sudden, or series of relatively saltational events, driven by internal causal factors or constraints?

Intriguingly, there is a similar gap between fins and tetrapod limbs. And once more, although no one doubts that fins and limbs are homologous, how the fin-to-limb transition came about is not known. Again as with the considerable gap between branchial rays and fins, there is a considerable morphological gap between fins and limbs while no intermediate fossils are known that might throw light on the transition.


Thus the familiar question arises: Was the fin-to-limb transition gradual or sudden? And was the tetrapod limb imposed by the external pressure of natural selection or by internal causal factors? The same might be asked about the origin of many other novelties in nature even where, as would seem to be the case here, a novelty is clearly homologous to some preexisting structure.

Beyond the scroll.

All in the family? III

The Little Lady of Flores Spoke from the Grave. But Said What, Exactly?
Denyse O'Leary

If Darwinian evolution is true, the human race should evolve into different species. Indeed, Darwin said that in Descent of Man. It is a feature, not a bug. But there is no clear evidence that it is happening. Thus, it would be most helpful to the argument if a new species (i.e., clearly human but not homo sapiens) was unearthed. Or at least, if the evidence was mixed, a species that could be argued into existence.In 2003, an international archeology team was excavating the Liang Bua limestone cave (pictured above) on the Indonesian island of Flores, between Sumatra and East Timor. At a six meters depth, they unearthed the skeleton of a tiny ancient woman, about thirty years old. She was a meter in height (a little over a yard), with the brain capacity of a small chimpanzee.

When the discovery was announced in October 2004, the buzz was that she represented a new human species. As such, she was "extreme," "spectacular," "startling," and "incredible." The Return of the King was released that year, so she was dubbed the "hobbit."

One researcher hoped that a "male" would turn up. His wish was swiftly granted -- by a National Geographic artist who offered an imaginative drawing of a "male" returning from the hunt, looking impressively feral, and distinctly other than human. By August 2007, Science was calling the dig "hallowed ground." In that year, modern humans were predictably fingered as the villains that wiped out Flores man. In addition, the find answered another unmet need: To Henry Gee, writing in Nature, it posed "thorny questions about the uniqueness of Homo sapiens."

The cave turned up more than bones; it revealed stone tools, remains of fires, and the bones of pygmy elephants and other feasts. So the hobbit woman and the other individuals later unearthed -- the oldest dating from perhaps 94,000 years ago -- apparently followed the same lifestyle as other ancient human groups. But then how did we decide that they were not just one of the vast variety of human types?

The key fossil's small brain was taken by many researchers as evidence that the Floresians must be a separate species. That and an odd-shaped wrist bone. But almost immediately, a competing narrative appeared. In November, leading Indonesian scientist Teuku Jacob (1929-2007) announced that the Flores hobbit was an "ordinary human" and "just like us," but possibly with mental defects. Jacob took the bones to his own lab, and returned most of them the following February, amid charges that he had severely damaged them.

He also damaged the orthodox narrative. And Nature wasn't having any of that "just like us" stuff. In March 2005, it triumphantly reported the results of a computer simulation that bolstered the new species claim, in a story titled "Critics silenced by scans of hobbit skull." But the critics' silence did not dispel lingering doubt about "Homo floresiensis."

Concern was raised that the ongoing controversy might be good for creationism. One researcher offered that "we certainly make it easy for them when we have disagreements like this one. I think that a lot of what has been said is going to have to be retracted. Given the amount of media attention, it just makes the field look incompetent." He concluded: "Nobody is on the side of the angels now."

Not even the angels, it seemed.

By March 2008, the scene had changed again. New Scientist told us, "Researchers have uncovered bones that could drive another nail into the Homo floresiensis coffin." The magazine's nail-and-coffin metaphor is a signal: Doubt is now fashionable, not forbidden. Why? Apparently, diminutive humans had "overrun" a nearby island as recently as 1400 years ago -- "but despite their size these people clearly belonged to our species."

Meanwhile, more recent reconstructions have suggested that Flores man looked like us, and that earlier artists' reconstructions may have distorted this fact:

Basically, chimps don't have human cheeks, the study argues, so past reconstructions of the hobbit's face botched its likely looks. Or past efforts fell into the trap of assuming all early modern human species resembled "wild men," "missing links" or "ape-men."

And on it goes. The old bones told no new tale.

To get a sense of the breadth of positions in the controversy, see "Is the Hobbit's Brain Unfeasibly Small?" (maybe not); "Compelling Evidence Demonstrates that 'Hobbit' Fossil Does Not Represent A New Species of Hominid"; "Researchers offer alternate theory for found skull's asymmetry" (malformed individual); "'Hobbit' Was an Iodine-Deficient Human, Not Another Species, New Study Suggests."

Meanwhile, the Neanderthals were becoming ever more dissatisfied with their treatment at the hands of taxonomists.

Original v.evidence lite physics?

What Does Beauty Have To Do with Physics?
By Sarah Scoles

As a Harvard undergraduate, Sarah Demers—now a professor at Yale University—didn’t have the job you would imagine of a young student of particle physics. She wasn’t running code, writing equations on whiteboards, or trawling data for statistically significant signals. Instead, she was sitting in a basement, transforming 10,000 sheets of gold-coated Mylar into an instrument that would go inside the Fermilab particle accelerator.

It was menial, tedious labor, and she was the only woman in the windowless room. Even after the transformation was complete, the work and the instrument itself didn’t scream “glamorous.” In its DIY, basement-built glory, the detector looked less like a sophisticated science instrument and more like someone toppled over a set of cheap garage shelves.

Before the job started, she thought she would hate it, and—worse—that she wouldn’t understand the underlying physics, that she was just messing around with foil sheets.


But she found that she did understand, and soon she could comprehend not only how the strange instrument worked, but also how it would help reveal fundamentals of physics. “I gave myself permission to think about underlying questions,” she says.
Inside the Fermilab particle accelerator, her instrument looked on as protons collided at near light-speed with their opposites—antiprotons—and the resulting particle shards decayed after the cataclysmic blast. By rewinding that action, physicists could dissect it in slow motion. From there, they could pick up its pieces, discover what matter is made of and the forces that hold it together, and pry it apart.

Despite the foil-wrapped contraption’s messiness, those close observations of the femtoscale explosions are what helped her see she beauty. “A lot of us go into science partly driven by how beautiful the theories are,” Demers says.

Physicists often describe their earliest experiences with the field as borderline spiritual, moments in which they realized that they—they!—can represent the world with math. They can describe how stars shrink to black holes, how hard you will hit your head if you slip on a banana peel, and how protons fall apart inside particle accelerators. That ability gives them a sense of control in the way that describing something gives humans dominion over it.

For many physicists, this fosters a desire to get to the very, very bottom of things: the theory of everything. Such a theory, many physicists often believe, should be beautiful, simple, elegant, aesthetically pleasing. All of the forces should fit under one umbrella; all particles need to emerge from a nested set of equations. No ifs, ands, buts, or loopholes. Physicists sometimes use these qualities, and their opposites—ugliness, caveats, asymmetries—as respective hot-and-cold indicators to guide them on the path toward understanding, describing, and conquering the universe.

The current gold standard for describing the nature of reality, the Standard Model, isn’t physicists’ ideal because, among other blemishes, it isn’t perfectly symmetric, and the way it glues fundamental forces together is a little kludgy. That’s partially why scientists have developed a new idea, called supersymmetry, which smooths and extends the Standard Model, giving each of those old-school particles a new-school “supersymmetric” counterpart.

Despite the fact that particle physicists have found no evidence of supersymmetry, they continue hunting for the elusive supersymmetric partners—partly because the theory is more aesthetically appealing than the Standard Model.

But not all physicists believe that beauty should count as indirect evidence in favor of an idea.

As Demers dug in to her research, she began to have doubts. Maybe it was okay for the universe to be a little bit ugly. And with that thought, Demers joined a faction of physicists who believe that the pursuit of beauty as truth may be leading the field of particle physics astray.

Semi-Symmetry
Marcelo Gleiser, a professor of physics at Dartmouth College, began his career the same way as Demers: searching for the underlying explanations of why the universe is the way it is. But about a decade ago, he felt Demers’s same uncertainty tugging at him. “You look outside, and what you see in nature is not really perfection and symmetry,” he says. “You see patterns and formats which are not exactly perfect. Animal, tree, cloud, face: They obviously have symmetry but not perfect symmetry. It’s not really perfection, but near perfection.”

“How contrived is too contrived? And how fine-tuned is too fine-tuned?”
He saw the blemishes in physics, too. There is more matter than antimatter, for example. If the two were perfectly balanced and symmetric, they would have annihilated each other like the particles in Demers’ detector, and the universe would be empty—there’d be no physicists to wonder why, or to high-five each other after the discovery of a beautiful but deadly cosmic balance. “Something happened during the history of the early universe to cause this,” he says. “That got me thinking that perhaps the insistence that we have in search of perfect symmetry is not a physics idea, but a bias.”

Demers’s epiphany took place as she was composing grant applications to fund her work after graduate school with the Large Hadron Collider, where the so-called “God particle” Higgs boson was discovered. Around 3,000 people worked on the ATLAS instrument team with her—attempting to discover physics that’s beyond the well-established Standard-Model. In the grant application, she also had to justify her experiment and the motivations behind it. Some of the reasons she jotted down, she realized, were purely aesthetic. It made her uncomfortable. “I personally had been sloppier about that than I should have been,” Demers says. “It struck me: You wonder, how equipped are we to be making aesthetic judgments given what we know now?” she adds. “How contrived is too contrived? And how fine-tuned is too fine-tuned?”

Millennia of Aesthetics
The human desire for a fine-tuned, aesthetically pleasing cosmos goes much further back than our ability to build particle accelerators. Plato believed the universe was made of geometry: simple, pure shapes that some deus snapped together to form a Lego-like reality. A sufficiently smart person, he reasoned, could unsnap those building blocks to reveal the fundamental forms.


Early astronomers also believed that planetary orbits were perfect circles. After all, in their view, God wouldn’t have doomed the planets to orbit along an imperfect path. Because every early astronomer started with this belief, it took Johannes Kepler six years to figure out that the evidence pointed to unappealing elliptical orbits instead. But when he allowed the experimental data to lead him toward a conclusion, he discovered a truth about the universe.After Kepler’s data-driven discovery, Isaac Newton created the theories of gravitational force that described how and why orbits actually trace ellipses, though his ideas again reached back toward aesthetic pleasure. The same gravity that makes apples fall onto our heads also makes Earth go around the Sun. One beautiful force to control them both.

In this kind of thinking, Gleiser sees a different version of the ancients’ god-driven commitment to perfect circles. And in modern scientists’ pursuit of further unification—like making the physics of atoms and subatomic particles work with the classical physics that governs the everyday world—he sees a renewed religious impulse. “The idea that there is a force that describes everything is sort of a monotheistic cultural vice that we have,” he says. “Growing up in a culture for two or three thousand years where there is a god and a central command of things—I think that’s deeply ingrained in people’s heads.” In some sense, physicists have replaced their one true, symmetrically-faced God with one true, symmetric theory.

Take Einstein, who in the early 1900s said that general relativity was too beautiful to be wrong. Or physicist Paul Dirac, who in the 1960s said that the elegance of an equation outweighed the outcome of an experiment. It’s as though they had both taken to heart what poet John Keats wrote in 1820: “Beauty is truth, truth beauty.”

For Demers and Gleiser, aesthetics as evidence loses its appeal when it is taken as…well…on par with evidence. For example, when the Large Hadron Collider failed to find any evidence of supersymmetry, many theorists tweaked their ideas about supersymmetry—saying, “Here’s why we don’t see any evidence”—rather than accepting that perhaps the evidence was pointing them elsewhere.Demers believes particle physics is in a data-rich era and that physicists should let data lead the way. As the Large Hadron Collider continues its run, it produces more and more evidence for experiments physicists like her to analyze—and then for theorists explain. “I think we may be more likely to win by the data just forcing us in a direction, as opposed to having some great idea that’s aesthetically motivated that pans out to be true,” she says. In other words, it isn’t a physicist’s job to write mathematical poetry expounding upon the platonic “universeness” of the universe. It’s their job to describe the physical reality that we interact with, that we have concrete experimental data about.

And so, while beauty may be truth, the science of physics isn’t actually the pursuit of truth, nor the quest for beauty. The universe may be, at its most fundamental, as perfectly balanced as a Shakespearean sonnet. But if the data from experiments suggests not a sonnet but a modern prose poem—which is no less pretty, just different, unconventional, and more complicated—it is still physicists’ duty as scientists to analyze it.

Agnostic Quests
In April 2015, after a two-year break for an upgrade, the Large Hadron Collider spooled back up. This summer, the accelerator—including the ATLAS experiment that Demers is part of—will conduct its second data-taking run at these higher energies with more particle collisions. By the end of the season, it will have recorded twice as much information as it did in all of 2015. In that data, says Demers, physicists should still search for evidence of the Standard Model and supersymmetry—she’s not opposed to those theories. But they should also go on “agnostic quests,” she says, where they don’t go looking for something in particular. Instead, they should just look, and see what they find.But some physicists may be reluctant to give up their beautiful theories, even if the data dictates they should. For example, while the Large Hadron Collider has so far failed to show evidence of supersymmetry, many have essentially said that the collision wasn’t powerful enough or that some small modifications are all that’s needed to fit the theory they love with the data they gathered.

“Supersymmetry has been around since 1974, for 42 years, and it doesn’t really have any evidence that it’s there. But people really bet their careers on this,” Gleiser explains. “Many physicists have spent 40 years working on this, which is basically their whole professional life.”

That may change in in ten years or so, he says, when further advances to the LHC could force the hangers-on to let go if the data they need doesn’t materialize. “If we don’t find evidence, people who still stick to it after that are doing it as a philosophical practice,” he says.

Of course, it’s certainly possible that the answers to life, the universe, and everything will be elegant. To physicists like Demers and Gleiser, that’s not the problem: The problem is the a priori assumption that it is so. And if the foundational principles of the universe turn out to be ugly or tedious, perhaps we can find the beauty beneath the mess.

Not as black as once thought?

Stephen Hawking says escape from a black hole is possible — kind of

Ali Sundermier 


Stephen Hawking has shaken up our understanding of black holes by announcing that actually, it might be possible to escape these greedy pits of spacetime.

"They are not the eternal prisons they were once thought," Dr. Hawking said in a talk last year. "If you feel you are trapped in a black hole, don't give up. There is a way out."

He posted his paper on arXiv, a pre-peer review site, in January. This month, the paper was finally published in the peer-reviewed journal Physical Review Letters.

Hawking's assertion that it is, in fact, possible to escape a black hole will not only transform our definition of them, it will also solve a longstanding riddle about what happens to the information that these mysterious space beasts devour.

Hawking radiation
A black hole is a monstrous warping of the fabric of space and time. It's a region where matter is almost infinitely compacted, and anything that gets too close is indiscriminately devoured.

And for a while, we believed that nothing - not even light - could escape its intense gravity.

In the 1970s, Stephen Hawking proposed that some things actually do wiggle free from the grasp of a black hole. When a black hole gulps up part of a particle-antiparticle pair, one half might escape, carrying away a tiny bit of the black hole's energy in the form of Hawking radiation.

Over time, a black hole will slowly leak out this energy, evaporating until it inevitably vanishes. Nothing would be left of the black hole except this mysterious radiation.


But then, what happens to all the information that swirled helplessly past the black hole's point of no return?
The information paradox
Until recently, Hawking believed that this information was lost forever. But our current understanding of modern physics states that it should always be possible to reverse time and piece together the present from the past like a puzzle.

"The Universe, like a kind of supercomputer, is supposed to be able to keep track of whether one car was a green pickup truck and the other was a red Porsche, or whether one was made of matter and the other antimatter," the New York Times reports. "These things may be destroyed, but their 'information' - their essential physical attributes - should live forever."

So if this is the case, all of the information inside the black hole should actually be preserved somehow. And if not, that means that black holes disobey the laws of modern physics. Then what's to say that other things don't do the same? That means that our memories might not be real: the "past" might be an illusion.


This is called the black hole information paradox, and it's been confounding scientists for decades. But Hawking thinks he might be on track to finding a solution to this.
'Hairy' black holes
Up until now, scientists thought that black holes were bald. But Hawking says that black holes might actually be surrounded by halos of 'soft hair,' Science Alert reports. This peach fuzz would preserve all the information of everything that ever fell into the black hole.

"That pattern, like the pixels on your iPhone or the wavy grooves in a vinyl record, contains information about what has passed through the horizon and disappeared," the New York Times reports.

But that doesn't mean you can dive headfirst into a black hole and expect to make it out alive. What's actually preserved is your information, not your physical body. And it doesn't have to be preserved intact, it can be all jumbled up beyond repair.


It's kind of like burning a book, the New York Times reports. The book might be reduced to nothing but smoke and ashes, but "with the right calculations, you should be able reconstruct the patterns of ink, the text."

A clash of Titans XXI

Time to end the state sponsored vengeance?Pros and Cons.

File under "Well said" XXIX

Education begins the gentleman, but reading, good company and reflection must finish him. John Locke

The simian stone age?

Monkeys Do Not Have a "Stone Age" Culture
Wesley J. Smith 

It is amazing how some in the sciences are so desperate to knock humans off the pedestal of exceptionalism. Ironically, a primary manner in which they seek to do this is by demonstrating how animals are like us -- indirectly admitting our special status.

Latest example? Monkeys supposedly have a "stone age culture" because some have used tools made of durable natural materials. From "Monkey 'Archeology' Reveals Macaque's Own Stone Age Culture," in New Scientist:

The world's first archaeology dig of an old world monkey culture has uncovered the tools used by previous generations of wild macaques -- a group of primates separated from humans by some 25 million years of evolution. The discovery means humans aren't unique in leaving a record of our past culture that can be pried open through archaeology.

Only a few decades ago scientists thought that humans were the only species to have worked out how to turn objects in their environment into useful tools. We now know all sorts of animals can do the same - but the tools of choice are usually perishable materials like leafs and twigs. This makes the origin of these behaviours difficult to study, especially when you consider that the record of hominin stone tool use stretches back more than 3 million years.

Burmese long-tailed macaques are a rare exception. They are renowned for their use of stone tools to crack open shellfish, crabs and nuts, making them one of the very few primates that have followed hominins into the Stone Age.

Please. Using stones does not make a culture.

Here are the "Seven Elements of Culture":

Customs: Are the written and unwritten rules of society. They can refer to a culture's laws, but also its moral and ethical expectations.
Religion: Unites people under a common belief system and values. Religion is the most important aspect of many people's lives, and is a major bonding factor within communities.
Government: Offers protection and order, and defines power and responsibility within a culture.
Language: Can act to join people of the same culture, but can also distinguish people of different sub-groups within a common culture.
Communication: Vital to the spread of culture, so you can see how having the same language is important in cultural terms.
Arts: Art and literature is one of the most powerful ways of spreading cultural knowledge and beliefs.
Economy: A culture's economy regulates what it needs to survive in terms of resources.

Using stones in the manner of tools? Nope.

And was anything really new learned in this dig? Not much.

We know from eyewitness accounts that these monkeys have been using tools for at least 120 years, so the study doesn't push the age of the behaviour back. But Haslam sees it as a first step towards digging deeper into the origins of the behaviour.

In other words, this is a big nothing burger.

The real human stone age culture included all seven elements, for example, explicit creativity (the incredible beauty seen in the cave paintings), the emergence of moral agency, the coming together of clans and tribes with governing rules, inventing, burying the dead (implying a spiritual belief), an aesthetic sense, evidenced by the making of jewelry, and on and on and on.


Monkeys using stones for tools? That's not culture, at least, not in the sense that humans create, mold, and shape it. Nice try fellas, but no cigar.

Universal common ancestry in the hot seat V

Vincent Torley Thinks I Have Egg on My Face
Ann Gauger 

Well, I must say I didn't expect to be honored by a 7500-word broadside by philosopher Dr. Vincent Torley, assisted by Dr. Josh Swamidass, Assistant Professor at Washington University. I guess they must have a lot of spare time. The reason for the post at Uncommon Descent? Both hold common descent to be absolutely, incontrovertibly, obviously true, and they apparently wish I would fall into line and stop embarrassing them by doubting common descent. They wish I would give up my "peculiar kind of intellectual obstinacy."

The argument is in the end all about common descent. (There are a few accusations of poor reasoning, obscuring the issue, and even a little bad faith along the way.) Look, intelligent design is not wedded to common descent. Neither is it wedded to a denial of common descent. Intelligent design states that there is evidence of design in the universe. I think we are in agreement on this point. In terms of biology, how the designer instantiated that design is still subject to debate, based on the strength of the evidence for each position.

As a biologist, I see evidence on both sides of the debate. The evidence is equivocal -- hence the fact that ID advocates take different positions on the subject. Yet common descent -- the idea that organisms descend from one or a few common ancestors -- is treated like a sacred cow by many scientists, and even, it appears, by some philosophers. Indignation arises that anyone would doubt it, would even have questions. Scientists take common descent as axiomatic, and accept evidence that is itself interpreted through a lens of common descent as proof of common descent. As a consequence, any evidence against common descent meets opposition and is explained away.

So when I see weak evidence for common descent I say so, as I did in a post here, "The Vitellogenin Pseudogene Story: Unequally Yolked." (Apparently Dr. Torley caught the reference but missed the yolk, as he repeatedly misstates my post's subtitle as "Unequally Yoked.") I wrote the aforementioned post because of weak evidence, and even an overstatement of the evidence by some.

The controversy began with the post on vitellogenin synteny, "Vitellogenin and Common Ancestry: Reading Tomkins," by Professor Dennis Venema at Trinity Western University, where I read some interesting arguments regarding cross-species synteny in the region of the chicken vitellogenin genes. Synteny is the term for the shared arrangement of genes along chromosomes from different organisms, and its existence is taken as evidence for common descent. Vitellogenins are egg yolk proteins, present and used in egg-laying organisms.

I followed up by reading the paper "Loss of Egg Yolk Genes in Mammals and the Origin of Lactation and Placentation," by David Brawand, Walter Wahli, and Henrik Kaessmann, on which Venema's post was based. (It's free access. You can verify all this yourself.) It's always a good idea to read the original material and evaluate the evidence for yourself. What I saw in Brawand et al. is what prompted me to write my post.

My dispute with Torley (and Venema) is at bottom a dispute about the scientific interpretation of data, or should be. Therefore I am going to go through the data in some detail, to show why I reached the conclusions I did with regard to the human "VIT1" pseudogene, and where we differ in interpretations. This essentially covers Torley's points 1 and 2. I will address the points 3-7 in later posts, so as not to burden the reader with excess length.


There are three chicken egg yolk genes, VIT1, VIT2, and VIT3, all expressed and made into protein because chickens lay eggs. The Brawand paper set out to see if there was any evidence for a vitellogenin presence in the human genome, with the idea that we are descended from an egg-laying animal. They looked in the region of our chromosome that is analogous to the chicken genome, and aligned the two against each other. A dotplot from the Brawand paper (see below) shows where the human (Y axis) and chicken (X axis) DNA sequences align. A perfect alignment (for example if human sequence was aligned against human) should show a diagonal solid line.




All figures taken from Brawand, D., Wali, W., and Kaessmann, H. 2008. Loss of Egg Yolk Genes in Mammals and the Origin of Lactation and Placentation. PLoS Biology (6) 507-517. Creative Commons license.

The top panel illustrates the VIT1 alignment between the two sequences, chicken and human, and the bottom panel VIT2 and VIT3. Black dots show where sequence similarity exists. The colored stripes indicate coding sequences (exons) for each "gene." In between in the white regions are the non-coding introns and intergenic spaces (sequences between genes). ELDT1, FP, SSX2IP, and CTBS are functional genes in both human and chicken and show sequence similarity and synteny in all coding sequences (the yellow stripes). Even some intergenic spaces show evidence of synteny. Where the synteny disappears is where the VIT1, VIT2, and VIT3 coding sequences should be.


I found the VIT1, VIT2, and VIT3 alignments to be ambiguous at best. However, in the supplemental materials for the Brawand paper is another representation of the syntenic regions where the human VIT1, VIT2, and VIT3 remnants should be. That makes things clearer. It is reproduced below, but click on the image to see the figure properly:



The bars colored red and black represent the chicken VIT genes, showing only their exons (the parts of the gene that contribute to making protein), alternating as red and black segments along the VIT sequences. (There are 35 exons in VIT1 and 2, 36 exons in VIT3.) Above each bar and running parallel to it are thin red lines, indicating where similarity has been detected, with insertions, deletions and stop codons necessary to make the sequence line up also indicated. To find this alignment they used "highly sensitive similarity search algorithms," and ran repeated trials. From the paper:

The best scoring alignment chain was determined from the 2,000 best local alignments for each VIT region using dynamic programming. Importantly, the combined alignments of VIT coding sequences of the best chain for each of the opossum VIT1-VIT3 regions (aligned to chicken) showed significantly higher alignment scores than the genomic background (introns and intergenic regions) in the chain, as assessed by a Mann-Whitney U test (P < 0.05). This suggests that the obtained (pseudogenic) VIT remnants from opossum are nonrandom sequence matches and represent true VIT sequences. In the eutherian [human and dog] comparison, VIT1 coding sequences showed significantly higher scores than the genomic background [reported as P < 0.05 elsewhere] (the alignable regions for the other two VIT genes may be too short to provide statistical significance -- VIT3 -- or represent spurious matches -- VIT2). [Emphasis added.]
There was very little actual sequence alignment data given for the human syntenic regions, just the 150 base sequence from exon 3 that I mentioned in my post. Since I was asked to provide the source of my analysis, here is it, as obtained in the paper in a supplementary figure; again, click on the image to see it better:


Full disclosure: this is the best-reported evidence they have for human synteny. The rest is unconvincing to me, though it may be convincing to others. Surely if they had a better or more extensive alignment they would have reported it. This by the way, I would assume is the stretch of DNA used by Jeff Tomkins in his analysis of the region.

Now for a general comment regarding the accusation of faulty statistics made against me by Torley and Swamidass. Here is the segment from Torley's post:

Professor Swamidass has two comments which are germane here. First, he points out that as a matter of standard practice, the data relating to similarity in the paper by Brawand et al. should be considered correct, unless proven otherwise. If Dr. Gauger thinks that the authors' claims of similarity are doubtful, then I would invite her to show the exact DNA sequence she used, so that interested readers can perform a BLAST by themselves (there is a website for this), to verify both the match to the vitellogenin chicken gene and to the human sequence. This doesn't resolve the issue of picking the right DNA sequence, but it is a start. Selecting the right parameters is important, too: if you use the wrong gapped parameter (a mistake Tomkins is notorious for making), then there will be discrepancies. [Emphasis added.]
I do not question the authors' data, but I do question their interpretation that it proves there is a VIT1 pseudogene in humans. Actually to be fair, they merely suggest it as evidence. They do not go much further than what I have quoted above: they point out a few deletions held in common by dogs, humans, and armadillo in the 150 base sequence I show above, arguing that they all share common ancestry. The bulk of the paper is about the remnants of opossum and platypus vitellogenin genes, perhaps because they recognize that the evidence is weak for dogs (for which they report no analysis I could find) and humans.

About the data being correct and my questioning it: All scientists are (or should be) taught in graduate school to critically evaluate conclusions. That is not the same as questioning original data, which I do not do. Questioning conclusions, evaluating them carefully to see if they are warranted, is something all scientists should do.

Again, I based my analysis on the data reported in the paper; I did not question the underlying data. The 150 base sequence I talked about was available as a supplementary figure in the paper itself, and I have already shown it to you. Careful reading of Brawand et al. would have revealed it -- it is the only sequence reported for human alignments. But since I am asked to provide the sequence I used, here it is. The 50 percent identity that is so disputed was simply calculated based on the percent identical positions for this 150 base alignment. I used the authors' own data. By the way, nowhere do they report a sequence identity for the region, probably because with poor alignment elsewhere, the percent identity would be considerably lower than 50 percent.

Lastly, I don't know where Torley's computer scientist friend Glenn Williamson got his figures, but they do not match the data reported in the paper. Says Williamson:

About 1,500 base pairs can be aligned with around 73% identity. That's much more than the 150 base pairs that Tomkins chose to focus on. Readers will recall that Tomkins claimed only a 62% identity, even for this short segment. [Emphasis in the original.]
If the alignment was as high as Williamson said over such a long stretch, surely it would have been reported by the authors. It certainly doesn't agree with the figures I have shown from the original paper itself. (See Figure S1 and S2.) The 150 base alignment shown in figure S2, with its 50 percent identity, is the little segment on the left side of VIT1, directly over exon 3 in Figure S1. There is no other alignment around it, let alone 1500 bases with 73 percent identity. I'll leave readers to judge whether Williamson's alignments are valid. But as Torley says, "if you use the wrong gapped parameter then there will be discrepancies."

Now for why I wrote the post. For this you will have to go to Dr. Dennis Venema's post that started it all, and which was mentioned earlier. (I do not think it is under the Creative Commons license so I won't reproduce his figure here.) I want you to compare his "redrawings" of the synteny between humans and chickens in the VIT1, VIT2, and VIT3 genes to the actual data reported in Brawand et al.'s paper. Does Venema's redrawing strike you as an exaggeration of the synteny for VIT1, as it did me? Compare it to the figures I have shown here from the original paper.

If all people did was to read Venema's post, the synteny would look pretty convincing. That's unfortunate. Those not trained in science will take his post at face value, and be convinced of VIT1 synteny and its status as a former vitellogenin gene. When the original data is examined, it's not nearly as convincing. Scientists have a duty to represent data accurately, even other people's data. Now I may not have access to information Dennis Venema has, so I will give him the benefit of the doubt. But I would be happier if he changed his figures, or revealed his source for any data that didn't come from the paper he cited.

Finally, Torley makes a point about my having commented that the opossum alignment might show synteny better than the human or dog sequence. I didn't discuss it in my post beyond that comment because it wasn't the focus of my argument. I will turn to the discussion of the alignment between opossum and other genomes with the chicken, and the evidence for pseudogenes in another post. I will also answer Torley's question about logical inferences, and offer him my own logical puzzle.

I will deal with his other accusations along the way.

Thanks for sticking with the nitty-gritty analysis, dear readers. It's up to you to decide what you think about human synteny with VIT genes, whether it is strongly or weakly supported by the evidence, and whether we are justified in considering alternate explanations.

Information and the design debate

Too much of a good thing?

Objection to Intelligent Design -- Universe Is Too Big, with Too Much "Wasted Space"

David Klinghoffer

Thoughtful reader Eric points me to a fine article over that The Stream by Tom Gilson, addressing an objection to ID:

We don't know whether anyone is enjoying the view from some other planet. For all we know, we might be the only observers. Whether we are or not, the vastness of it all has led some skeptics to ask, why would God waste so much space on so few living creatures? Is this really a mark of intelligent design? It might surprise you to hear that I like that question, but I do: I enjoy answering it.

One of the better-articulated versions of that question goes like this:

Doesn't the way that 99.99999999% of the universe is absolutely inhospitable to any kind of life show you that it wasn't made for anybody? It is easy to imagine how a universe could have been more intelligently designed, with less wasted space and energy and more hospitality for life.

This objection is formulated by John R. Shook, of the Center for Inquiry, who also teaches philosophy at the University of Buffalo ("The Disappearing God"). Gilson goes on:

First, the "scientific" viewpoint of all this emptiness, when taken in full perspective, makes no strong statement against design. Quite the contrary, actually. I could mention the universe's fine-tuning for life, for one thing. For another, we know now that a large universe is necessary for life, at least according to physics as we understand it.

On that, Gilson cites "the principle of the galactic habitable zone."

[Its] implications include the principle that a certain amount of empty space, but not too much, is essential for life to thrive. (That's admittedly an oversimplification which I make for the sake of space here on the blog, but not, I take it, a distortion.) So it is premature at best to suppose that large amounts of space "inhospitable to any kind of life" really mean that "it wasn't made for anybody."

Second, that idea is not just premature; it's also incredibly short-sighted with respect to who Christians understand God to be. Is God concerned about the waste of energy and space?

Eric adds:

I think there is at least one other point that could be made. How does one recognize when something is rare? We see the extremely unusual state of this privileged planet precisely because it is in stark contrast to a vast inhospitable universe.

And we can see that contrast because we are also unusually suited for observation and scientific discoveries. Our state is both fine-tuned and knowable as fine-tuned.

Contrary to what Dr. Shook imagines, a vast universe is a key component in at least one line of argument for intelligent design. Articulated by Michael Denton and others, this argument points to the unique fitness of the universe and of our planet for upright bipeds like ourselves. The whole thing appears set up for us, and only for us. The vaster the cosmos, the more dramatically that point is underlined.

Denton's current focus is on the fitness of the universe for fire-using creatures like us. See the short documentary Fire-Maker.

What exactly is the size of the universe, as we observe it? Wikipedia says:

The proper distance -- the distance as would be measured at a specific time, including the present -- between Earth and the edge of the observable universe is 46 billion light-years (14 billion parsecs), making the diameter of the observable universe about 91 billion light-years (28×109 pc).

As Evolution News observed yesterday in a biological context, ID critics often end up playing the role of naïve theologian: What they "seem to want is a metric with The Human Body as God Would (or Should) Have Made It at one end of the measuring stick. As Dilley and Nelson have pointed out, contemporary Darwinian evolutionary thinking borrows heavily from theology for its justification." In this case it should be The Universe as God Would (or Should) Have Made It.

I'd want to ask John Shook, is it like going to the mall and looking for a pair of pants with the right waist and inseam measurements? 91 billion light-years is too big to be intelligently designed. Is there a size that would be too small? Just right?

Merely to ask such questions is to see how absurd the contention is that the universe has too much "wasted space."

Darwinism vs. the real world XXXIII

Liver Function and Its Effects
Howard Glicksman 

Editor's note: Physicians have a special place among the thinkers who have elaborated the argument for intelligent design. Perhaps that's because, more than evolutionary biologists, they are familiar with the challenges of maintaining a functioning complex system, the human body. With that in mind, Evolution News is delighted to offer this series, "The Designed Body." For the complete series, see here. Dr. Glicksman practices palliative medicine for a hospice organization.

Tim (not his real name) was a hard-working, hard-drinking man who had never stayed attached to anyone. He had contracted viral hepatitis which, combined with his alcohol abuse, had caused him to develop chronic liver disease. He had been hospitalized several times when I first met him at his sister's home after he was placed in hospice care. He was lying in a recliner looking pretty weak with a yellowish tinge to the whites of his eyes and skin. He had marked muscle wasting, scattered scratches and bruises on his arms, and a large belly with swollen red legs. I saw that he was confused and had problems expressing himself, so I turned to his sister and her son to get the history.

They told me that Tim had been declining for the last several weeks and that, although he had stopped drinking a few months ago, each time he came out of hospital he was worse than the last time. Now he needed a lot of help to dress, bathe, and use the bathroom. He could barely stand, even with significant assistance, to pivot and transfer to a wheelchair. He was more prone to confusion and slept most of the time, seemed to be itchy, ate very little and complained of abdominal and leg swelling and pain. When I examined him, not only was he confused and jaundiced, I also found that he had a fever, a quick pulse, and a relatively low blood pressure. I also noted that not only was his abdomen full of fluid but the redness in his swollen legs was due to infection.

His sister brought out the results of some of his recent blood work, which showed a very low serum albumin, elevated bilirubin and ammonia levels, and a moderate delay in his clotting test. I sat down with Tim's sister and nephew to explain the situation and what we might be able to do for him to keep him comfortable.

Next to the brain, the liver is the most versatile organ, performing over five hundred different tasks, and each is important for survival. Since the liver is capable of regeneration and has a large functional reserve, it usually requires a loss of over eighty percent of its cell function for the symptoms and signs of chronic liver disease to manifest. It is the liver that handles the metabolism of carbohydrates, proteins, and fats for the energy and nutrient needs of the body. It produces numerous different proteins for specific tasks and, using enzymes, chemically breaks down drugs, hormones and other substances so the body can maintain control of its chemical environment.

Evolutionary biologists are good at imagining how an ultra-complex organ like the liver could have come into being by talking about how it looks, but not how it actually works within the laws of nature to keep the body alive. But real numbers have real consequences and by using Tim's case to highlight just five of the over five hundred functions of the liver, we will see what would have happened to our earliest ancestors without any one of them. After all, evolutionary biology claims that life came about by chance and laws of nature alone, so it must explain how transitional organisms survived as the liver gradually acquired these vital functions while macroevolution was taking place.

First, the liver helps the body break down red blood cells and, using enzymes, chemically converts hemoglobin into bilirubin. It then takes bilirubin and joins it with cholesterol and other chemicals it produces to form bile. The liver sends the bile into the intestine so it can absorb fats and with it fat-soluble chemicals like vitamin A, for vision, vitamin D, for bones and calcium metabolism, and vitamin K, for clotting, all of which were necessary for our earliest ancestors. Just as we see for Tim, when the liver cells aren't working properly, the bilirubin they produce backs up and moves into the blood, making the bilirubin level rise and causing the whites of the eyes and the skin to turn yellow (jaundiced). People who are jaundiced often feel tired and weak, with a poor appetite and nausea, and may feel itchy.

Second, the liver produces albumin which represents over sixty percent of its entire protein output. One role for albumin is to help transport minerals like calcium and magnesium, fatty acids and other lipids, and steroid hormones like estrogen, progesterone, and testosterone in the blood so they can travel to where they are needed in the body. But one other very important function of albumin is to maintain the blood volume by keeping enough water in circulation. As blood enters the arterial side of the capillary under pressure and moves to the venous side, water is naturally pushed out of the circulation through the pores within the walls of the capillary and into the interstitial fluid, like soft boiled potatoes through a ricer.

Since albumin cannot escape from circulation through the walls of the capillary, it naturally applies an osmotic pull back on the water trying to leave, acting as a counterbalance to the pressure pushing the water out. The degree of osmotic power applied by albumin to pull back on the water trying to escape from circulation is directly related to how much albumin is in the blood. When the liver doesn't produce enough albumin, more water tends to move out of the circulation and into the interstitial fluid, which reduces the blood volume and can cause blood pressure to drop. One of the main causes of Tim's low blood pressure and increased fluid in his abdomen (ascites) and legs (edema) was due to a very low level of albumin in his blood.

Third, besides albumin and other transport proteins, the liver produces most of the clotting factors. Hemostasis is the process by which the body prevents itself from bleeding, something that would have been vital for the survival of our earliest ancestors. Damage to the blood vessel wall triggers the muscles surrounding it to contract and close off the opening as much as possible. It also causes the platelets in the blood passing by to stick together, forming a soft plug to cover the opening and limit blood loss.

But, for many blood vessel injuries, this is not adequate to achieve hemostasis. The clotting factors must swing into action to produce a fibrin clot strong enough to permanently seal the defect, stop the bleeding, and allow healing to take place. When the clotting factors are released from the liver into the blood they are inactive and do not interact with each other unless they encounter a damaged blood vessel. This is very important because if fibrin clots formed within normal blood vessels they could block blood flow and lead to organ damage and death. When the clotting factors encounter a damaged blood vessel, and the platelet plug trying to seal it, this triggers them to interact like dominos to form a fibrin clot in a process called the coagulation cascade. When the liver isn't making enough clotting factors, this makes the body prone to bleed easier as we see with Tim, whose clotting test was prolonged. That was why his arms were bruised due to minimal trauma from scratching.

Fourth, another set of proteins the liver makes is complement which consists of over thirty proteins that, when activated, work together to help the immune cells fight infection. Just like the clotting factors, the complement proteins are inactive when the liver releases them into the blood. Encountering microbial infection triggers them to interact like dominos to aid in the immune defense of the body. They increase inflammation in the area of infection, kill microbes, and attract immune cells to the battlefield and help them attach to microbes so they can literally swallow and destroy them. When the liver isn't working as well as it should, it produces less complement, which along with other factors, makes the body more susceptible to infection. Clinical experience shows that this would have made the survival of our earliest ancestors impossible.

Fifth, another important job for the liver is to convert ammonia, a highly toxic byproduct of protein metabolism, into urea, so it can be released from the body through the kidneys.

This requires five specific enzymes working together in what is called the urea cycle. Elevated blood levels of ammonia are toxic to the nervous system and the absence of any one of these five enzymes would have made life impossible for our earliest ancestors. When the liver isn't working properly, it may allow ammonia, and other toxic substances that it usually metabolizes, escape into the blood, causing a condition called hepatic encephalopathy. In its milder form, this manifests as irritability, poor attention, anxiety, and insomnia. But if the ammonia level rises further, this can progress to imbalance, lethargy, confusion, slurred speech, difficulty swallowing, and be fatal. Returning to Tim, we see that with his confusion, difficulty speaking, and need for lots of assistance, that he is probably showing signs of hepatic encephalopathy.

Having detailed to his sister and nephew what was going on with Tim, I also explained that his leg infection could be responsible for his functional decline and confusion. In other words, if we could treat some of his problems with medications and provide him with good nutrition and support, he may improve and be able to live a little longer. We started him on antibiotics to treat his infection, diuretics to push excess salt and water out of his body and reduce the swelling in his legs and abdomen, and medication to reduce the ammonia level in his blood. Over the next several weeks Tim's condition improved so that he was lucid, had a better appetite, and could be up on his own with a walker. The transformation was remarkable and he became very animated about how he had a "new lease on life."


Tim's nephew was due to go back to college for his pre-med courses in biology and he was perplexed. He believed in neo-Darwinism, and was exposed to the rhetoric that those who don't believe Darwin really don't understand science. But what he had learned about the liver and just five of its vital functions, and what he had seen happen over the last several weeks, gave him pause. He had seen someone who believes in intelligent design prove his knowledge of how science, and life, really works by bringing his uncle back from the brink. I told him that being a physician means having the responsibility to seek out and speak the truth so that those who are vulnerable will not be misled and being humble enough to admit that we don't always have all of the answers, and probably never will.