Electric bacteria for design.

By Jasmin Fox-Skelly

 

Some microbes have developed the ultimate stripped-down diet. They do not bother with food or oxygen. All they need to survive is pure electrical energy.
They often live in muddy seabeds or along the banks of rivers. Finding them is easy: biologists can coax them out of hiding by sticking an electrode into the sediment. The bacteria nearest to the electrode will even grow biological equivalents of electrical wires out of their bodies, so that other microbes further away can hook up to the electricity source. It is effectively a living power grid.
What's more, it appears that we can all benefit from this microscopic grid. Among other things, it might provide an effective way to deal with toxic waste and other forms of environmental pollution.
 

Electricity-eating microbes might sound like something straight out of a science fiction novel. In fact their behaviour is not quite as exotic as it might first appear.

                
All lifeforms on Earth – even humans – must harness energy if they are to remain alive. This energy comes in the form of electrons, the same tiny negatively-charged particles that create a current when they zip around electrical wires in a circuit.
We humans, along with most other organisms on this planet, get our electrons from sugars in the food that we eat. In a series of chemical reactions that happen inside our cells, the electrons are released, and ultimately flow into oxygen – the same oxygen which we have just breathed in through our lungs. That flow of electrons is what powers our bodies.
This means that the challenge for all creatures is the same. Whether the organism is a single-celled bacterium or a blue whale, it has to find a source of electrons, and a place to dump them to complete the circuit.
But what happens when there is no oxygen to dump your electrons onto?
Many organisms live in low-oxygen environments and so must use alternative electron dumps. For some, that means "breathing" metals instead of oxygen.
In 1987 Derek Lovley and his lab at the University of Massachusetts stumbled across the first of these bacteria on the banks of the Potomac River near Washington DC.
The microbes, called Geobacter metallireducens, were getting their electrons from organic compounds, and passing them onto iron oxides. In other words they were eating waste – including ethanol – and effectively "breathing" iron instead of oxygen.
Of course, this is not breathing as we would recognise it. For one thing, bacteria do not have lungs. Instead, the bacteria pass their electrons to metal oxides that lie outside the cell.
They do this through special hair-like wires that protrude from the cell's surface. These tiny wires act in much in the same way that copper wire does when it conducts electricity. They have been dubbed "microbial nanowires".

 

Geobacter bacteria are able to survive on energy sources entirely unavailable to most lifeforms.

They are even able to effectively "eat" pollution. They will convert the organic compounds in oil spills into carbon dioxide, or turn soluble radioactive metals like plutonium and uranium into insoluble forms that are less likely to contaminate groundwater – and they will generate electricity in the process.
In fact, some even see a future in which microbial fuel cells power devices like smartphones using seaweed, urine or sewage as their only food source: the ultimate in recycled energy.
In 1988, a year after Lovley's discovery, microbiologist Kenneth Nealson of the University of Southern California found a second electron-excreting bacterium.He was investigating a strange phenomenon in Oneida Lake in New York State. The lake contains manganese, which reacts with the oxygen in the air to form manganese oxide.
However, Nealson did not find as much manganese oxide as he was expecting. Some of it was missing. The culprit, it turns out, was Shewanella oneidensis.
This bacterium breathes oxygen when it is available, but in the muddy banks of the lake where oxygen is scarce it instead passes its electrons directly onto manganese oxide, producing a stream of electricity. It can do the same thing with other metals like iron.
Just how the bacteria were doing this was a mystery until very recently.
Under the microscope, Shewanella appear to have long thin hair-like extensions of their outer membrane. These filaments were at first thought to conduct electrons along them like a copper cable, much like Geobacter. However, it turns out that the long filaments are only conductive when dried out in a lab.
Instead Shewanella appear to shuttle electrons out of their cells using transport molecules called flavins and "stepping stone" proteins embedded in the outer membrane called cytochromes.

So far we have only talked about bacteria that produce electricity when they breathe. But these electron-excreting microbes are not the only ones that researchers have found.
While most organisms get their electron fix from carbohydrates, some bacteria can harvest electrons in their purest form. They can effectively "eat" electrons from minerals and rocks. In a way, they are getting their electrical energy straight from the socket.
Annette Rowe, a graduate student of Nealson, has found six new bacterial species on the ocean floor that can live off electricity alone. All are very different to one another, and none of them is anything like Shewanella or Geobacter.Rowe took samples of sediment from the seabed in Catalina Harbour off the Californian coast, brought them back to the lab and inserted electrodes into them. She then varied the voltage of the electrodes to see whether the bacteria in the sediment would "eat" electrons from the electrode, or discharge electrons on to it.
She found that, when no other food source was available, the bacteria would happily take electrons directly from the electrodes. In their natural habitat, the bacteria likely take their electrons directly from iron and sulphur in the seabed.
Examples of electron-eating bacteria found by Rowe include Halomonas, Idiomarina, Marinobacter, and Pseudomonas of the Gammaproteobacteria, and Thalassospira and Thioclava from the Alphaproteobacteria.

Many more electron-loving bacteria have now been found. In fact all you have to do is stick an electrode in the ground and pass electrons down it, and soon the electrode will be coated with feeding bacteria. Experiments show that these bacteria essentially eat or excrete electricity.
The holy grail of electricity-loving bacteria would be having a species that could both eat and excrete electrons, and so could exist entirely on electricity alone without any other energy source
According to Lovley, that grail has already been discovered. Some species of Geobacter, he says, can both directly transfer electrons to electrodes and also directly accept electrons from them.
In 2015, we learned that electron-eating and electron-excreting microbes can actually team up and pass electrons between each other, wiring themselves into a common electrical grid.
At the bottom of the ocean lie vast reserves of methane, released by microbes feeding on the remains of dead algae and animals as they sink down from the surface. If the methane escaped into the atmosphere the gas would exacerbate global warming, but luckily a consortium of microbes seem to keep it in check.
Different species of bacteria and archaea – ancient single-celled microbes similar to bacteria in many ways – team up to degrade the methane before it can get the surface.Gunter Wegener from the Max Planck Institute for Marine Microbiology in Bremen wondered how the process worked. He collected samples of the microbes
, which live at temperatures of 60C on the ocean floor, and put them under a scanning electron microscope.
The microscope revealed thin wire-like structures protruding from the bacterial cells. Although only a few nanometres wide, the wires were several micrometres long, which is much longer than the cells themselves.
It seems that the bacteria use these nanowires to hook up with the archaea.
The archaea feed on electrons from methane, oxidising the gas to generate carbonate. They then pass the electrons on to their partner bacteria along the nanowires, which act like power cables. Finally the bacteria deposit the electrons onto sulphate, producing energy that the cell can use in the process.
The researchers have now identified the genes that coded for the production of these nanowires. It is only when methane is added as an energy source that the genes are switched on and the nanowires form between bacteria and archaea.
This ancient form of electronic cooperation between the two types of microbe may have evolved billions of years ago, when the Earth's atmosphere was oxygen-free.
"One of the most interesting developments in the area of microbes eating and breathing electrons is the concept of direct interspecies electron transfer," says Lovley. "This is when microorganisms wire themselves together to share electrons, permitting them to carry out reactions that neither would be able to carry out individually."
Lovley and his lab have also discovered other communities of bacteria that are able to pass electrons directly to each other.

In the lab, Lovley showed that two species of Geobacter – G. metallireducens and G. sulfurreducens – survive by forming a conductive network of nanowires, through which electrons can be shuttled. G. metallireducens takes electrons from ethanol and then passed them directly to G. sulfurreducens using this electrical grid.                     
Cable bacteria live on sea floors and river beds where there is little oxygen. Without oxygen, they have nowhere to donate their electrons.
In a more extreme version of this process, some bacteria can link up to form long "cables".To cope with this the cable bacteria, which belong to the family Desulfobulbaceae, form chains, one cell in diameter, extending thousands of cells and distances of several centimetres – a huge distance for a bacterium only 3 or 4 micrometres long – until they finally reach a habitat with oxygen.
The first bacterium in the chain, which lives in a low-oxygen habitat, takes electrons from sulphide and passes them onto the next bacterium. This bacterium then passes the electrons on to the next cell, and so on until the final bacterium in the chain can finally pass the electrons onto oxygen.
This means that bacteria living in seabed mud where no oxygen penetrates can access oxygen dissolved in the seawater above simply by "holding hands" with other bacteria. Running along the chains of bacteria are ridges that connect the cells together, possibly allowing electrons to flow between them.
Other bacteria rely on rocks and minerals to do all the hard work for them when it comes to eating and dumping electronsBacteria have been seen to attach themselves to conductive materials, such as the iron-rich mineral magnetite, in order to pass electrons between each other through the magnetite. It is thought that chains of magnetite can form, bridging the gap between the electron-donating and the electron-accepting bacteria.
The environments these bacteria occupy may seem exotic, but electron-eating and -breathing microbes can also be found in more familiar settings.
For instance, they have been discovered in the digesters that convert brewery wastes to methane. Inside one such brewery, Geobacter metallireducens was directly transferring electrons to another bacterium, Methanosaeta harundinacea, which was then passing the electrons on to carbon dioxide.
It is even possible that microorganisms in the human gut electrically interact with cells in the gut lining.Just why have the bacteria evolved this neat trick?Being able to survive on electrons alone is a smart way of coping when resources and food are scarce, as can be the case at the bottom of the ocean or deep underground. Here, there is not quite enough energy for an organism to grow, or compete, but there is enough for it to exist – just about.
If life exists on other worlds, such as Mars or Jupiter's moon Europa, it will probably be in similarly sparse environments. Astrobiologists searching for evidence of extraterrestrial life might be particularly interested in electricity-eating and electricity-excreting microbes.
Whether or not such alien life is ever found, electricity-eating and -excreting bacteria here on Earth are still a significant discovery. All you need to do is provide them with an electrode onto which they can "breathe" electrons, and they have the potential to steal electrons from toxic waste, oil spills and nuclear waste, cleaning up our waste and generating electricity in the process.
Not bad for simple single-celled organisms.BBC Earth

Has nutritition science let cholesterol out of the dog house?

High cholesterol 'does not cause heart disease' new research finds, so treating with statins a 'waste of time'

Henry Bodkin

 

Cholesterol does not cause heart disease in the elderly and trying to reduce it with drugs like statins is a waste of time, an international group of experts has claimed.

A review of research involving nearly 70,000 people found there was no link between what has traditionally been considered “bad” cholesterol and the premature deaths of over 60-year-olds from cardiovascular disease.
Published in the BMJ Open journal, the new study found that 92 percent of people with a high cholesterol level lived longer.The authors have called for a re-evaluation of the guidelines for the prevention of cardiovascular disease and atherosclerosis, a hardening and narrowing of the arteries, because “the benefits from statin treatment have been exaggerated”.
The results have prompted immediate scepticism from other academics, however, who questioned the paper’s balance.
High cholesterol is commonly caused by an unhealthy diet, and eating high levels of saturated fat in particular, as well as smoking.

It is carried in the blood attached to proteins called lipoproteins and has been traditionally linked to cardiovascular diseases such as coronary heart disease, stroke, peripheral arterial disease and aortic disease.
The authors have called for a re-evaluation of the guidelines for the prevention of cardiovascular disease and atherosclerosis, a hardening and narrowing of the arteries, because “the benefits from statin treatment have been exaggerated”.
The results have prompted immediate scepticism from other academics, however, who questioned the paper’s balance.
High cholesterol is commonly caused by an unhealthy diet, and eating high levels of saturated fat in particular, as well as smoking.

It is carried in the blood attached to proteins called lipoproteins and has been traditionally linked to cardiovascular diseases such as coronary heart disease, stroke, peripheral arterial disease and aortic disease.
Co-author of the study Dr Malcolm Kendrick, an intermediate care GP, acknowledged the findings would cause controversy but defended them as “robust” and “thoroughly reviewed”.
“What we found in our detailed systematic review was that older people with high LDL (low-density lipoprotein) levels, the so-called “bad” cholesterol, lived longer and had less heart disease.”
Vascular and endovascular surgery expert Professor Sherif Sultan from the University of Ireland, who also worked on the study, said cholesterol is one of the “most vital” molecules in the body and prevents infection, cancer, muscle pain and other conditions in elderly people.
“Lowering cholesterol with medications for primary cardiovascular prevention in those aged over 60 is a total waste of time and resources, whereas altering your lifestyle is the single most important way to achieve a good quality of life,” he said.
Lead author Dr Uffe Ravnskov, a former associate professor of renal medicine at Lund University in Sweden, said there was “no reason” to lower high-LDL-cholesterol.
But Professor Colin Baigent, an epidemiologist at Oxford University, said the new study had “serious weaknesses and, as a consequence, has reached completely the wrong conclusion”.
Another sceptic, consultant cardiologist Dr Tim Chico, said he would be more convinced by randomised study where some patients have their cholesterol lowered using a drug, such as a stain, while others receive a placebo.
He said: “There have been several studies that tested whether higher cholesterol increases the risk of heart disease by lowering cholesterol in elderly patients and observing whether this reduces their risk of heart disease.
“These have shown that lowering cholesterol using a drug does reduce the risk of heart disease in the elderly, and I find this more compelling than the data in the current study.”
The British Heart Foundation also questioned the new research, pointing out that the link between high LDL cholesterol levels and death in the elderly is harder to detect because, as people get older, more factors determine overall health.
“There is nothing in the current paper to support the author’s suggestions that the studies they reviewed cast doubt on the idea that LDL Cholesterol is a major cause of heart disease or that guidelines on LDL reduction in the elderly need re-valuating,” a spokesman said.

On Learning to disagree without being disagreeable.

In the Evolution Debate, Not Listening Happens in One Direction, Not Two

David Klinghoffer

 

An eloquent post from Terry Teachout, the Wall Street Journal theater critic, might as well be a commentary on Doug Axe's observations this morning ("Public Opinion Is the Ultimate Peer Review"). Teachout (whom I had the privilege of working with at National Review long ago) laments the divorce between cultures symbolized by Red and Blue states. He recalls a time before half the country was so fiercely committed to regarding itself as Enlightened while dismissing the other half as Benighted, hopelessly so, or worse. Anyway that's how I would characterize it.

Many, perhaps most Americans of my generation (I was born in 1956) lived in places whose residents included people who read, liked, listened to, and thought all sorts of things, and who voted differently, even unpredictably, on election day. As a result, we learned to get along with one another, and sometimes we even learned from one another. At the very least, we learned -- up to a point -- to be reasonably tolerant of each other's crotchets.
More and more, though, we don't live together and we don't listen to each other. As a result, the modest but real tolerance of the past is increasingly giving way to attempts at outright repression, or (more often, at least for now) [a] sniggeringly dismissive attitude...

He refers to a Washington Post story deploring a prominent person's well-known appetite for fast food:

This "news" story is, in its minor but nonetheless revealing way, illustrative of the condition that now increasingly prevails in American society, which is that those who disagree no longer have anything to say to each other. Fact-based argument has been replaced by reflexive contempt. Nor should this be in any way surprising. In a totally polarized political environment, persuasion is no longer possible: we believe what we believe, and nothing matters but class and power. We are well on the way to becoming a land of jerking knees.
Never before have I felt so strongly that Americans are talking past instead of to one another.

The dividing line extends from food to faith, from politics to science. Oh, most certainly it includes science. Doug Axe, in his post, responds to a Caltech commencement address by Atul Gawande, the surgeon and New Yorker staff writer. To someone like Gawande, these sentences by Dr. Axe are a counterintuitive shot across the bow: "People aren't stupid. Science is a public enterprise, and public acceptance has always been its most significant seal of approval."
The theme of Axe's forthcoming book, Undeniable -- How Biology Confirms Our Intuition That Life Is Designed, is the validity of ordinary intuition as a tool in judging science. That idea is anathema to Americans on the other side of the worldview divide that Terry Teachout describes. For them, people -- "mere people," as Axe puts it ironically -- are indeed stupid.
In fact the deplorable stupidity of half the population is a pillar of faith for the Enlightened. The Benighted show their benightedness by trying to have a conversation with the Enlightened, not realizing that their "conversation" partner isn't even listening. For the Enlightened, it often seems, "nothing matters but class and power."
We see this in the discussion, such as it is, of intelligent design versus unguided Darwinian evolution. In this debate about an ultimate question, the mystery of human and biological origins, for one side "Fact-based argument has been replaced by reflexive contempt."
I would only offer this addendum to Terry's observations, from our experience in the context of the evolution controversy. Scientists open to evidence for design offer abundant "fact-based arguments," only to be greeted by a "sniggeringly dismissive attitude." They are not talking past us. By that I mean, design advocates genuinely register and understand, even if they reject, arguments from the other side. The "reflexive contempt" does not operate equally in both directions.

universal common ancestry in the hot seat. VI

The Opossum's Tale: The Torley Saga, Cont.

Ann Gauger

Background: There has been an on-going discussion between Dr. Vincent Torley, a philosopher, and myself on the subject of pseudogenes, synteny, and common descent. These are technical terms and the arguments may seem abstruse, but the topic is important because of its implications. Those who hold to common ancestry accept that, at the very least, each major group of animals is descended from a common ancestor, and some hold that the common ancestry goes all the way back to the first cell. The question is whether we share common ancestry with chickens and opossums, and by implication, with chimpanzees. What we have been discussing for all these posts is this: How strong is the evidence that we have the remnants of an egg yolk protein, vitellogenin, in our genome? Do we come from an egg-laying ancestor?

 

In a post at Uncommon Descent, "Consider the Opossum," Vincent Torley took me to task for a number of reasons, but chief among them was that I ignored the evidence for synteny between the opossum and chicken vitellogenin (VTG) genes. (Synteny refers to the alignment of sequences in order and identity between stretches of DNA from two species.) This evidence came from the Brawand paper. I had been meaning to address the opossum data, but events (Torley's post) got in the way. So rather than debate, I'll make it simple. The evidence for synteny in opossums and chickens is good. Surprised? I had already planned on saying this before the latest information about human alignments came up.
Now, is this synteny between chicken, opossum, and human evidence for common descent? Could be. Remember, some intelligent design proponents accept common descent based on evidence like this. They may think that this particular scenario happened by purely naturalistic processes. But they also acknowledge that at least some processes could not happen in an unguided fashion. These people may accept common descent but also affirm the necessity and detectability of design. Anyone who affirms the detectability of design is by definition a friend of intelligent design, even if not publicly so.
Others think for various reasons that a designer guided the process, but in such a way that the design is undetectable. They think that the designer has hidden the evidence of design, and may even go so far as to question why he would do such a thing, since everything looks like a purely natural process. This viewpoint might as well be full-blown materialistic neo-Darwinism.
Then there are people who reject common descent to one degree or another. They may proffer different explanations for sequence similarity. Synteny, for example, can be the result of a need for a particular chromosomal organization or structure. Thus, gene expression regulatory blocks can lead to the appearance of conserved synteny. It is also possible that the apparent remains of vitellogenin genes may be being used for other purposes. The vitellogenin protein itself is multi-purpose -- it and its derived proteins are involved in the innate immune response in fish. Has anyone looked into this in higher vertebrates? Probably not. There is evidence of long non-coding RNA (lncRNAs) in the region of similarity, plus other possibly functional elements. In response to a comment from Professor Josh Swamidass, I note that lncRNAs can act in cis (on their own region, rather than a distant location) making their location on the chromosome important. It is not therefore beyond the realm of possibility that any similarities we see among opossums, chickens, and humans are there for functional reasons. The signal we see could be the result of essential sequence-dependent function in the region, with different sequences shared between species. I agree with Swamidass that all these proposals are possibilities only and would need to be demonstrated as real and functional.
But even if it's the case that this region shares the remnants of egg yolk genes and ancient synteny, common descent from an egg-laying ancestor is not the only possible reason there could be old genetic code lying around. It depends on your model for how the designer acts. Consider an analogy with how human programmers work. A programmer I know says that coders routinely use old code in new programs. It's hard to write new code, but easy to use code that has already been designed, and to plug it into the new program. It takes time to get rid of the unused code that comes along for the ride so to speak. It's easier to just leave it alone. (My pardon to my friend if I did not express properly what he said.) In fact, in our case, the designer might have plans for that unused code further down the road. I should also say, there is no intent by the programmer to deceive anyone who later comes along to deconstruct the code as to its origin. It looks like ancient code shared between organisms, but it's not due to common descent. It's simply the way the designer works.
In all these cases, it could be that once the old code has been created it is subject to the same process of neutral or near-neutral evolution as for standard neo-Darwinian evolution. Mutations happen all the time -- most are largely neutral, with little or no effect, so they tend to accumulate. Unless there is some reason to maintain a particular sequence without change (because it has a necessary function), its sequence will tend to drift and degrade, like the vitellogenin genes in opossum, dog, and human are proposed to have done. This will tend to mimic the signal of synteny and pseudogenization in the vitellogenin gene.
This analogy will probably irritate the materialists among us. So let me propose another possibility. The signal we see could result if there is essential sequence-dependent function in the region, with different sequences shared between species.
I acknowledge that common descent is an appealing explanation for this synteny. I know the strength of the common descent argument. I am also aware of its weaknesses, which I will address in my next post. The evidence for common descent is mixed, as we shall see. The reason I doubt common descent is not because of the ways that it succeeds, but rather because of the ways that it fails. And I am still inclined to accept the design explanation because I expect to see function rather than junk in our genomes.
Finally, let me give an answer to one very specific question posed by Vincent Torley, as put to him by Josh Swamidass, as an example of the difference in approach to the data.

Why is the genetic signal stronger in the opossum (a marsupial mammal) than in human beings, who are placentals? The common descent model has an answer to this question: the various lines of mammals made the transition away from eggs at different times, so they inactivated their yolk genes at different times. How does the design model answer this question?

First of all, marsupials are placentals also, but of a different kind. Second, my response to the question is that I hope Torley and Swamidass are not making the mistake of thinking of marsupials as partway up the evolutionary ladder, therefore closer to their egg-laying roots than are eutherian mammals. If common descent is true, the theory says that eutherian mammals and marsupials share a common egg-laying ancestor that diverged from the chicken lineage a long time ago, so present day marsupials and mammals are equidistant from chickens in evolutionary time. There can be no a priori prediction about which should have a vitellogenin pseudogene with closer resemblance to an egg-laying chicken's gene, without prior, independent knowledge of when egg laying was lost in either lineage.
The Brawand paper is the only paper I could find that assigns a date to when egg yolk proteins were lost in each lineage. It was the reason for their study. They based their estimate on the genetic signal of the degree of degeneracy between the sequences. It is faulty reasoning to say the reason for the greater degeneracy is because of earlier loss of egg-laying, when the reason for the dating of the egg-laying loss is based on said degeneracy.
Common descent cannot explain why egg-laying genes were lost earlier in one lineage than another, since it could have happened either way. Or not at all. See above.
From a design perspective, I would say the reason for the difference in apparent inactivation times is because each animal has a different design. How the DNA is used may differ.
So now on to the next and final explosive post. Stay tuned. It's my riposte to the "explain and predict" test for common descent versus common design offered by Torley. And I am done with talking about egg yolk proteins.
Editor's note: For previous replies by Dr. Gauger to Dr. Torley, see here and here.
 

 

Trying to fool all of the people all of the time?

Public Opinion Is the Ultimate Peer Review

Douglas Axe

 

In his recent Caltech commencement address, surgeon and New Yorker staff writer Atul Gawande offered advice on how to rebuild the public's confidence in the scientific community. He ends with the right idea, but only after showing that even he needs to take that idea more seriously.

What does truth-seeking look like? Gawande concludes by saying that "it is the effort not of a single person but of a group of people -- the bigger the better -- pursuing ideas with curiosity, inquisitiveness, openness, and discipline." I agree... more wholeheartedly now than I would have back in 1990, when I was wearing the Caltech mortarboard.

Back then I considered scientists to be a breed apart -- a privileged class of gifted people trained to think in a different way. That this different way of thinking was better than other ways of thinking didn't have to be proclaimed aloud. We all knew it with quiet confidence. Had Gawande been the commencement speaker in 1990, I would have interpreted his call for inclusivity and openness as a call for members of this elite community to conduct themselves in a way that would sustain our elevated status.

The "we" versus "they" stance that characterizes Gawande's speech would have resonated with me then, I think. When he said, "People are prone to resist scientific claims when they clash with intuitive beliefs," I would have understood the coded language. "People" here means mere people -- those who haven't been inducted into the superior scientific "way of being." So, what are we scientists to do when those unenlightened outsiders don't follow us? Using smaller words and speaking more slowly only goes so far, because "once an idea has got embedded and become widespread, it becomes very difficult to dig it out of people's brains -- especially when they do not trust scientific authorities."

Yes, indeed. People tend to be wary of that kind of brain surgery.

Maybe the better way to restore public confidence is to abandon the condescending mindset and embrace a much more radically inclusive view of science. Maybe the moms Gawande referred to -- the ones who jumped to the conclusion that vaccines were dangerous -- aren't all that different from professional scientists who jump to the conclusion that public dissent is dangerous. Gawande gave five handy tips for writing people off as pseudoscientists, but instead of alienating people by dismissing them in this way, what if we were to view public opinion as the ultimate form of peer review?

If the safety of well-studied vaccines and the danger of forgoing them are observable facts, perhaps we should trust public peer review to affirm this. Indeed, it already has. Gawande mentioned the tragic human cost of a drop in vaccination rates in the US from 1989 to 1991. Ten years after that drop, Gallop results showed that "parents with the most information, both positive and negative, are most likely to get their children vaccinated." And this public verdict has held. According to a recent Pew Research Center report: "A vast majority of Americans view childhood vaccines as safe."

People aren't stupid. Science is a public enterprise, and public acceptance has always been its most significant seal of approval. Professional scientists should embrace this by doing more free sharing of information and less complaining about public opinion.

Editor's note: Dr. Axe is Director of Biologic Institute and author of the forthcoming book Undeniable -- How Biology Confirms Our Intuition That Life Is Designed (HarperOne). Undeniable will be published on July 12, but you can pre-order before then and participate in an exclusive, private conference call with Dr. Axe and talk-show host Michael Medved. You'll also receive digital versions of three complete books from Discovery Institute Press.

 

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.