On proteomics

Imagine: 60 Million Proteins in One Cell Working Together
Evolution News & Views


Scientific nomenclature follows a quirky path. First we had the gene. Then, scientists thought it would be convenient to lump all genes of an organism into a category called the genome (for gene + soma, L. body from chromosome). When epigenetics entered the discussion, we now had the epigenome, along with derivative terms genomics and epigenomics. Don't forget proteins -- though, they needed a term for the set of all proteins in a cell: the proteome.

The study of that is called proteomics. These days you can read about the lipidome (the totality of lipids in a cell), the metabolome (the metabolic players in a cell), and even the interactome (all the interactions in a cell). All these subjects merge into a higher-level category called -omics. The interaction of all omics categories is called economics (not really; that part is a joke).

Now that the genome is familiar, the study of proteomics is coming of age. Two recent papers show why proteomics is attracting so much attention. In a Nature review, Ruedi Aebersold and Matthias Mann show how "Powerful mass-spectrometry-based technologies now provide unprecedented insights into the composition, structure, function and control of the proteome, shedding light on complex biological processes and phenotypes." What can we expect with this new knowledge? Without referring to evolution once in their article, they list design-based benefits of proteomics:

The integration of various omics approaches and many perturbations will generate exponential flows of disparate data types. This will necessitate commensurate advances in bioinformatics and computational proteomics, which will be powered increasingly by machine-learning technologies while retaining their ability to generate biological insights. In this regard, the journey from single-protein analysis to a true understanding of the proteome and the importance of proteotypes will be long, challenging and exciting. [Emphasis added.]
Their first paragraph shows some of that excitement. Here are some "wow" facts they share about the proteins in a tiny yeast cell:

Collectively, proteins catalyse and control essentially all cellular processes. They form a highly structured entity known as the proteome, the constituent proteins of which carry out their functions at specific times and locations in the cell, in physical or functional association with other proteins or biomolecules. A proliferating Schizosaccharomyces pombe cell contains about 60 million protein molecules, which have abundances that range from a few copies to 1.1 million copies per expressed gene. Across the species, proteins constitute about 50% of the dry mass of a cell and reach a remarkable total concentration of 2-4 million proteins per cubic micrometre or 100-300 mg per ml (ref. 2). The extensive proteome network of the cell adapts dynamically to external or internal (that is, genetic) perturbations and thereby defines the cell's functional state and determines its phenotypes. Describing and understanding the complete and quantitative proteome as well as its structure, function and dynamics is a central and fundamental challenge of biology.
Aebersold and Mann take a "systems biology" view of the proteome, an inherently design-friendly perspective. Instead of viewing each protein molecule separately, they look at the proteome as an "integrated system." All these millions of proteins cooperate to contribute to the life and health of the cell, responding dynamically to perturbations, each playing its role to provide energy from nutrients, deliver cargo, translate and maintain genetic information, remove waste, and replicate. One surprising result comes from the systems biology view:

Present technology already enables analysis of the complete protein inventory of biological systems, including cell-type-specific proteomes of mammalian organs. One outcome of in-depth proteomics studies has been a demonstration of the extent to which diverse cellular systems have similar proteomes, with few proteins being uniquely detectable in specific situations. This surprising finding is supported by the Human Protein Atlas, a large-scale antibody-based study that also reports ubiquitous expression. The identity of cells and tissues therefore seems to be determined primarily by the abundance at which they express their constituent proteins, and perhaps by the manner in which the proteins are organized in the proteome, rather than the presence or absence of certain proteins.
Organization by Chance?

The ID-friendly findings of the "top down" systems approach contrast with statements in a second paper in Nature about "bottom up" protein design. Huang, Boyken, and Baker discuss "The coming of age of de novo protein design" wherein researchers hope to not only tinker with existing proteins, but develop brand new ones from first principles. To do that, they need to understand how an amino acid sequence determines folding patterns.

This paper is interesting because it relates to the work of Douglas Axe that resulted in a paper in the Journal of Molecular Biology in 2004. Axe answered questions about this paper earlier this year, and also mentioned it in his recent book Undeniable (p. 54). In the paper, Axe estimated the prevalence of sequences that could fold into a functional shape by random combinations. It was already known that the functional space was a small fraction of sequence space, but Axe put a number on it based on his experience with random changes to an enzyme. He estimated that one in 1074 sequences of 150 amino acids could fold and thereby perform some function -- any function.

The new paper in Nature seems to point to a much smaller functional space. The authors say,

It is useful to begin by considering the fraction of protein sequence space that is occupied by naturally occurring proteins (Fig. 1a). The number of distinct sequences that are possible for a protein of typical length is 20200 sequences (because each of the protein's 200 residues can be one of 20 amino acids), and the number of distinct proteins that are produced by extant organisms is on the order of 1012. Evidently, evolution has explored only a tiny region of the sequence space that is accessible to proteins. And because evolution proceeds by incremental mutation and selection, naturally occurring proteins are not spread uniformly across the full sequence space; instead, they are clustered tightly into families. The huge space that is unlikely to be sampled during evolution is the arena for de novo protein design. Consequently, evolutionary processes are not a good guide for its exploration -- as discussed already, they proceed incrementally and at random. Functional folded proteins have been retrieved from random-sequence libraries, but this is a laborious (and non-systematic) process. Instead, it should be possible to generate new proteins from scratch on the basis of our understanding of the principles of protein biophysics.
Since 20200 is about 10260, and the space actually sampled by living organisms is 1012, the numbers differ by at least 240 orders of magnitude for proteins of length 200, or about 183 orders of magnitude the 150-amino-acid chains Axe used. No wonder the authors say that "the natural evolutionary process has sampled only an infinitesimal subset" of sequence space.

The authors have nothing but their imagination to suggest that evolution restricted its search to functional clusters. Any random search has no possible chance, using all the atoms in the universe for the entire age of the universe, of finding a functional cluster in such a vast space. Dembski said that any search for a target that has less than 1 chance in 10150 exceeds the universal probability bound; it will never happen anywhere in the entire history of the universe.

Axe's estimate of one in 1074, one must note, referred to mutations to existing proteins in the universal proteome of all organisms. When considering random chains of amino acids in a primordial soup, however, Steve Meyer noted in Signature in the Cell (pp. 210-212) two other requirements. The amino acids must be one-handed, and they must form only peptide bonds. Applying generous probabilities of 0.5 for handedness and 0.5 for peptide bonds, Meyer reduced the probability for a lucky functional protein chain of 150 amino acids to one in 10164, far beyond the universal probability bound (p. 212).

With these numbers in mind, note the incredible faith that Huang, Boyken, and Baker invest in blind chance. We end with this quote:

Proteins mediate the fundamental processes of life, and the beautiful and varied ways in which they do this have been the focus of much biomedical research for the past 50 years. Protein-based materials have the potential to solve a vast array of technical challenges. Functions that naturally occurring proteins mediate include: the use of solar energy to manufacture complex molecules; the ultrasensitive detection of small molecules (olfactory receptors) and of light (rhodopsin); the conversion of pH gradients into chemical bonds (ATP synthase); and the transformation of chemical energy into work (actin and myosin). Not only are these functions remarkable but they are encoded in sequences of amino acids with extreme economy. Such sequences specify the three-dimensional structure of the proteins, and the spontaneous folding of extended polypeptide chains into these structures is the simplest case of biological self-organization. Despite the advances in technology of the past 100 years, human-made machines cannot compete with the precision of function of proteins at the nanoscale and they cannot be produced by self-assembly. The properties of naturally occurring proteins are even more remarkable when considering that they are essentially accidents of evolution. Instead of a well-thought-out plan to develop a machine to use proton flow to convert ADP to ATP, selective pressure operated on randomly arising variants of primordial proteins, and there were also hundreds of millions of years in which to get it right.

Now ponder that. They are duly impressed by the intricate molecular machines that proteins make in the cell, yet their worldview does not allow them to consider this as evidence for design.

On channelling your inner scientist.

A Nobel for the original technologist?

How About a Nobel Prize for the Intelligent Designer?
Evolution News & Views

There's a simple logic about the Nobel Prize for Chemistry awarded this week, noted already here by David Klinghoffer: human attempts at engineering molecules to perform work are feeble imitations of what living cells have done perfectly since life first appeared on earth.

The Royal Swedish Academy of Science awarded the Nobel Prize in Chemistry to Jean-Pierre Sauvage (University of Strasbourg, France), Sir J. Fraser Stoddart (Northwestern University, Illinois), and Bernard L. Feringa (University of Groningen, the Netherlands) for their work in creating artificial molecular machines. All the news media have been talking about it, congratulating them on their well-deserved recognition. But think about how simple their designs are to date:

Sauvage in 1983 linked two molecular rings together.

Stoddart in 1991 "threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle."

Feringa in 1999 "got a molecular rotor blade to spin continually in the same direction."

The work, of course, didn't stop there. Stoddart used his little wheel and axle to design a tiny lift, an "artificial muscle" and a molecule-based computer chip. Feringa built a "nanocar" of sorts. It's pretty remarkable to be able to construct and direct a device that's 1,000 times smaller than the diameter of a human hair. Even though nobody has come up with the "killer app" yet, the Nobel Committee sees a lot of potential in these initial steps:

2016's Nobel Laureates in Chemistry have taken molecular systems out of equilibrium's stalemate and into energy-filled states in which their movements can be controlled. In terms of development, the molecular motor is at the same stage as the electric motor was in the 1830s, when scientists displayed various spinning cranks and wheels, unaware that they would lead to electric trains, washing machines, fans and food processors. Molecular machines will most likely be used in the development of things such as new materials, sensors and energy storage systems. [Emphasis added.]
Designers of these devices will undoubtedly use intelligence to get them to work properly. So then how did life's molecular machines originate? Nothing created by the winners even approaches the complexity and efficiency of life's molecular machines, which continue to challenge and fascinate the best minds in science.

The Nobel Prize Committee asked Bernard Feringa what inspired him to work on molecular machines. In the transcript from the phone call, interviewer Adam Smith asked him:

AS: So you describe your work as being inspired by nature?
BF: Ja, of course. If you look at the cells in our body or the functioning of the organism, it is flabbergasting. It is fantastic to see how this intricate machinery works. And when I'm taking about motors, as we focus on motors, if you look at the essential functions in the cell, like cell division, like transport, like making your muscles move, bacteria that go to food or [unclear ...] it's all controlled by molecular motors, and so the biological motors, and the biological machinery, is so crucial to all these functions. And of course we get great inspiration from that, while we as chemists are extremely good in building all kinds of materials, and that is what intrigued me.

The comparison is clear: three human designers of artificial machines were inspired by the "fantastic" and "flabbergasting" and "intricate" machinery going on inside the cells of their own bodies. They get to split a million dollars for their simple Lego-like constructions. What does the designer of the cell get?

In a word, insults. How would you like it if your best work was called a product of blind chance? That's essentially what two papers in the Proceedings of the National Academy of Science (PNAS) do when considering the origin of ATP synthase -- possibly the most efficient machine in the universe (see our animation).

In the first PNAS paper, "Biophysical comparison of ATP synthesis mechanisms shows a kinetic advantage for the rotary process," four researchers from the University of Pittsburgh basically say that ATP synthase evolved because rotation was more efficient.

The ATP synthase (F-ATPase) is a highly complex rotary machine that synthesizes ATP, powered by a proton electrochemical gradient. Why did evolution select such an elaborate mechanism over arguably simpler alternating-access processes that can be reversed to perform ATP synthesis? We studied a systematic enumeration of alternative mechanisms, using numerical and theoretical means. When the alternative models are optimized subject to fundamental thermodynamic constraints, they fail to match the kinetic ability of the rotary mechanism over a wide range of conditions, particularly under low-energy conditions. We used a physically interpretable, closed-form solution for the steady-state rate for an arbitrary chemical cycle, which clarifies kinetic effects of complex free-energy landscapes. Our analysis also yields insights into the debated "kinetic equivalence" of ATP synthesis driven by transmembrane pH and potential difference. Overall, our study suggests that the complexity of the F-ATPase may have resulted from positive selection for its kinetic advantage.
This is like saying that cars evolved wheels, tires, and shock absorbers because it makes them run better. Their "systematic enumeration of alternative mechanisms" sure didn't include intelligent causes.

The second paper, "Rotation of artificial rotor axles in rotary molecular motors," is even more flagrant in its design denial. Nine authors from universities in Tokyo think it was easy for a simple rotary engine to become an efficient rotary engine by chance.

F1/V1-ATPases are sophisticated molecular machines that convert the motion of a stator cylinder driven by sequential ATP hydrolysis to rotation of a central rotor protein. Here, we reveal the rotation of artificial rotor proteins composed of exogenous rod proteins that show no apparent sequence similarity with the native axles. The estimated torque by the artificial rotor in the stator ring of V1 was almost identical to that by the native axle protein. These results demonstrate that the principle of rotational motion by these molecular motors relies solely upon the coarse-grained interaction between the rotor and stator. These findings imply that the ancient F1 or V1 motor domain has evolved from a poorly designed motor protein more readily than initially assumed.
It implies no such thing. All their lab work was intelligently designed; on what basis can they conclude that some "ancient... poorly designed" motor got better by chance? They provide no mechanism by which that could happen, not even natural selection. Instead, they say, "the current consensus view of the field is that the interfaces of molecular motor systems have sophisticated designs at an atomic level through molecular evolution."

Yet the design principles are the same. Notice what Nature's congratulatory article says:

The Nobel winners' work -- and other chemists' nanomachines -- have also had an impact on researchers' understanding of nature, Astumian says. In particular, the artificial systems have helped to demonstrate that all chemically-powered molecular machines, whether synthetic or biological, work according to the same principles: by selectively harvesting the random jiggles of Brownian motion, rather than pushing against them.

Intelligent design theory, we repeat, cannot speak to the identity or nature of the designer. Our purpose here is to unmask the inconsistency in thinking by materialists. They will congratulate human designers of simple machines and give them millions of dollars for their highly gifted and intelligent work. But when it comes to awarding credit for molecular machines of far greater sophistication, they give the prize to "molecular evolution."

On the Nobel committee's design inference.

Intelligent Design: Nobel Prize for Chemists who Synthesized Molecular Machines
David Klinghoffer

On this year's Nobel Prize winners in chemistry, pioneers in nanotechnology, thoughtful reader Eric beats us to the punch:

You've likely noticed that the chemistry Nobel Prize has been awarded to three chemists for the contributions to the study of molecular machines. They made impressive progress in being able to carefully arrange molecules so as to make machines that work.
As I read some of the articles about their work, I notice statements about how it required exceptional insight, great skill, and much intentional work to devise ways to arrange molecules so that they will function usefully.

Yet we are expected to believe on faith that uninterested and unthinking natural processes accidentally produced cells filled with coordinated functioning molecular machinery.

Right. We've called irreducibly complex molecular machines "prima facie evidence for intelligent design," posing a mystery addressed by the revolutionary thinking of Michael Behe. See our upcoming documentary Revolutionary: Michael Behe & The Mystery of Molecular Machines. For doing things nature is supposed to have done by a series of fortunate accidents, meanwhile, these synthetic chemists -- Jean-Pierre Sauvage, J. Fraser Stoddart and Bernard L. Feringa -- received the highest honor that science has to offer.

From the Royal Swedish Academy of Sciences, which recognizes the trio for their "design and synthesis of molecular machines":

The first step towards a molecular machine was taken by Jean-Pierre Sauvage in 1983, when he succeeded in linking two ring-shaped molecules together to form a chain, called a catenane. Normally, molecules are joined by strong covalent bonds in which the atoms share electrons, but in the chain they were instead linked by a freer mechanical bond. For a machine to be able to perform a task it must consist of parts that can move relative to each other. The two interlocked rings fulfilled exactly this requirement.
The second step was taken by Fraser Stoddart in 1991, when he developed a rotaxane. He threaded a molecular ring onto a thin molecular axle and demonstrated that the ring was able to move along the axle. Among his developments based on rotaxanes are a molecular lift, a molecular muscle and a molecule-based computer chip.

Bernard Feringa was the first person to develop a molecular motor; in 1999 he got a molecular rotor blade to spin continually in the same direction. Using molecular motors, he has rotated a glass cylinder that is 10,000 times bigger than the motor and also designed a nanocar.

The New York Times talked with famed synthetic chemist James Tour, who has advanced this work with his own nanocar design ("3 Makers of World's Smallest Machines Awarded Nobel Prize in Chemistry"). Tour is a signer of our "Dissent from Darwinism" list, but of course they don't mention that:

James M. Tour, a professor of chemistry at Rice University in Houston, said the Nobel would bestow legitimacy on the field and help convince people that nanomachines are not just fantastical science fiction of the far future.
"No one is making money on these right now, but it will come," he said. "These men have established and built up the field in a remarkable way."

Dr. Tour predicted that the first profitable use of the technology might be machines that open up cell membranes in the body to deliver drugs. "It's really going to be quite extraordinary," he said.

That is exciting. Tour has also observed that his experience of this new technology underlines the enigma of life's origin. On chemical evolution, he has written in an admirably slashing style:

Life requires carbohydrates, nucleic acids, lipids, and proteins. What is the chemistry behind their origin? Biologists seem to think that there are well-understood prebiotic molecular mechanisms for their synthesis. They have been grossly misinformed. And no wonder: few biologists have ever synthesized a complex molecule ab initio. If they need a molecule, they purchase molecular synthesis kits, which are, of course, designed by synthetic chemists, and which feature simplistic protocols.
Polysaccharides? Their origin?

The synthetic chemists do not have a pathway.

The biologists do not have a clue.

He calls for exposing students to this fact:

Those who think scientists understand the issues of prebiotic chemistry are wholly misinformed. Nobody understands them. Maybe one day we will. But that day is far from today. It would be far more helpful (and hopeful) to expose students to the massive gaps in our understanding. They may find a firmer -- and possibly a radically different -- scientific theory.
The basis upon which we as scientists are relying is so shaky that we must openly state the situation for what it is: it is a mystery.

The origin of life is a "mystery," yet among faithful materialists, stating that plainly is akin to a thought crime, a concession to the deplorable "creationists." Not an advocate of intelligent design, Tour nevertheless acknowledges that what nature accomplished by synthesizing life puts what he does in the laboratory in the shade:

Designing nanoncars is child's play in comparison to the complexity involved in the synthesis of proteins, enzymes, DNA, RNA, and polysaccharides, let alone their assembly into complex functional macroscopic systems.

Meaning no disrespect, what these three newly minted Nobel winners did is also child's play compared to whatever succeeded in minting the first life. The implications of that are profound, but naturally ignored by the popular science media.

Broken scales?

Judges Struggle With Their Own Conscience When Required to Ignore Conscience of Others

 

The presiding judge of the Suwon District Court wept as she read the prison sentence for 21-year-old Chang-jo Im, a conscientious objector to military service. Although the judge had handed down verdicts that day in five other criminal cases without any signs of distress, the injustice of this case moved her to tears. Having no other option, she sentenced this young man, one of Jehovah’s Witnesses, to 18 months’ imprisonment.

Every month, judges in South Korea face the same scenario. A young man identifies himself in court as a conscientious objector, and regardless of his personal circumstances, the judge pronounces the expected sentence of 18 months’ imprisonment. In his decision regarding one conscientious objector, Judge Young-sik Kim states: “The justices hardly believe that they are ‘punishing criminals’ when they deal with conscientious objectors.” The conflict he felt caused him to question the validity of the draft evasion statute as a sentencing guideline for conscientious objectors.

• Witnesses sentenced to prison each month for conscientious objection: 40-50
• Witnesses now imprisoned for conscientious objection: 602
• Total of Witnesses imprisoned for conscientious objection since 1950: 17,840

South Korea refuses to recognize the right of conscientious objection to military service and has made no provision for alternative civilian service. Judges in South Korea cannot avoid this recurring dilemma and must convict conscientious objectors as criminals. Judges are also aware that the UN Human Rights Committee has ruled in several cases—involving 501 young men—that South Korea is violating its international commitments to respect fundamental human rights by prosecuting and imprisoning conscientious objectors. As a result, a growing number of judges grapple with their own conscience as they impose prison sentences on young Christian men whose conscience does not allow them to engage in military service.

At this time, six district court judges have referred conscientious objection cases to the Constitutional Court of South Korea, though the Constitutional Court ruled as recently as 2011 that the military service law is constitutional. The judges’ decisions also address practical concerns.

What some judges have said about . . .

• The morality of imprisoning a person who objects to war for reasons of conscience

  “The ultimate goal of protecting freedom of conscience by the Constitution as a fundamental right is to protect individuals’ conscience, which form the basis for human worth and dignity. . . . Though their decision to reject military service does not harmonize with the majority’s idea, it would be difficult to argue that their decision amounts to a serious antisocial or antinational crime that deserves strict sanction by directly invoking the criminal punishment.”–Judge Hye-won Lim, Suwon District Court, February 21, 2013, 2012Chogi2381.

  “Deciding the relationship between oneself and others . . . [and] giving serious consideration to the ‘value of human existence’ is an integral process of forming one’s character. It also embraces the decision not to deprive anyone of his or her life, even under an armed conflict. If those [who have made] such decisions are forced to perform the military duty or compelled to take up arms and are invariably subjected to punishment if they refuse to perform such a duty, it would amount to denying their rights and their identity. Surely it violates human dignity.”–Judge Young-hoon Kang, Seoul North District Court, January 14, 2013, 2012Chogi1554.

• Whether recognizing the right of conscientious objection weakens national security

  “There is no substantial and specific evidence or data available that the adoption of the system of alternative service would undermine national security and equality of imposing the burden of military duty.”–Judge Gwan-gu Kim, Changwon Masan District Court, August 9, 2012, 2012Chogi8.

  “There is no sufficient reason to claim that national security will be severely endangered to an extent that it would be impossible to protect human dignity and [the] value of all citizens when a minority, including Jehovah’s Witnesses, . . . refuses to take up arms and perform military training. In fact, the defendant . . . has already refused to perform military duty despite punishment. If the claim [were] sufficiently grounded, national security and human dignity and the value of all citizens would already be in serious danger.”–Judge Seung-yeop Lee, Ulsan District Court, August 27, 2013, 2013Godan601.

• How this issue can be resolved

  “The administrative branch and the National Assembly are capable and able, when the Constitutional Court holds that the provision of this case is against the Constitution, to take into consideration both national security and freedom of conscience and legislate laws that recognize conscientious objection to military service and at the same time strengthen national security.”–Judge Young-sik Kim, Seoul South District Court, July 9, 2013, 2013Chogi641.

  “There will be neither loss of military force nor significant effect on national security as long as the alternative service system is carefully designed and implemented to avoid draft evasion under the pretext of conscientious objection.”–Judge Seong-bok Lee, Seoul East District Court, February 20, 2014, 2014Chogi30.

How will the Constitutional Court respond?

These judges ask the Constitutional Court to provide an answer for their troubling dilemma on the issue of conscientious objection. At present, the Court has granted admissibility in 29 cases, including two that involve 433 men.

What will the Constitutional Court determine in these cases? Will South Korea’s highest court recognize the right of conscientious objection to military service, opening the way for new legislation? If it does, it will honor its international commitments, its own Constitution, and dignify the consciences of many—bringing relief to hundreds of young men unjustly imprisoned.

Suboptimal design or suboptimal science?You make the call

#6 of Our Top Ten Evolution Stories of 2014: Phys.org Says the Argument for Suboptimal Design of the Eye "Is Folly"

Casey Luskin

 

In 2010, the pro-ID website Access Research Network (ARN) posted its Top Ten Darwin and Design Science News Stories of the year, and its No. 1 story was a paper in Physical Review Letters, "Retinal Glial Cells Enhance Human Vision Acuity." Why was this article ARN's top story for the year? Because it found that special "Müller glia cells" sit over the retina, acting like fiber-optic cables to channel light through the optic nerve wires directly onto the photoreceptor cells.

This refuted the old objection to intelligent design that the vertebrate eye is "poorly designed" because the optic nerve extends over the retina instead of going out the back of the eye. These cells ensure that there is no loss of visual acuity due to the presence of the optic nerve, as the paper found, revealing the retina "as an optimal structure designed for improving the sharpness of images." As New Scientist put it at the time, these funnel-shaped cells "act as optical fibres, and rather than being just a workaround to make up for the eye's peculiarities, they help filter and focus light, making images clearer and keeping colours sharp." We also reported on this here.

Now a new paper in Nature Communications, "Müller cells separate between wavelengths to improve day vision with minimal effect upon night vision," has expanded upon this research, further showing the eye's optimal design. According to the paper, Müller cells not only act as optical fibers to direct incoming light through the optic nerve, but are fine-tuned to specific wavelengths to ensure that light reaches the proper retinal cells. From the Abstract:

Vision starts with the absorption of light by the retinal photoreceptors -- cones and rods. However, due to the 'inverted' structure of the retina, the incident light must propagate through reflecting and scattering cellular layers before reaching the photoreceptors. It has been recently suggested that Müller cells function as optical fibres in the retina, transferring light illuminating the retinal surface onto the cone photoreceptors. Here we show that Müller cells are wavelength-dependent wave-guides, concentrating the green-red part of the visible spectrum onto cones and allowing the blue-purple part to leak onto nearby rods. This phenomenon is observed in the isolated retina and explained by a computational model, for the guinea pig and the human parafoveal retina. Therefore, light propagation by Müller cells through the retina can be considered as an integral part of the first step in the visual process, increasing photon absorption by cones while minimally affecting rod-mediated vision. (Amichai M. Labin, Shadi K. Safuri, Erez N. Ribak, and Ido Perlman, "Müller cells separate between wavelengths to improve day vision with minimal effect upon night vision," Nature Communications, DOI: 10.1038/ncomms5319 (July 8, 2014).)

The paper presents Müller cells as a direct answer to the view that the vertebrate eye has a suboptimal wiring:

[T]he mammalian retina and the peripheral retina of humans and primates are organized in a seemingly reverse order with respect to the light path. This arrangement places the photoreceptors, responsible for light absorption, as the last cells in the path of light, rather than the first. Therefore, the incident light must propagate through five reflecting and scattering layers of cell bodies and neural processes before reaching the photoreceptors. This 'inverted' retinal structure is expected to cause blurring of the image and reduction in the photon flux reaching the photoreceptors, thus reducing their sensitivity. It has been recently reported that retinal Müller cells act as light guides serving to transfer light across the retina, from the vitreo-retinal border towards the photoreceptors.

How do Müller cells accomplish this feat? The article continues: "A single Müller cell collects light at the vitreo-retinal surface from an extended retinal region, and guides it onto one coupled cone, located at its distal end." The shape of the Müller cells -- wide at the top where it collects light, and narrow at the bottom where it delivers light to the rods and cones -- presents a potential optimization tradeoff between day vision (which depends more on efficient light transmission to the cones) and night vision (which depends more on efficient light transmission to the rods).

They then ask an engineering question: "Can this cost-benefit optimization problem between day vision and night vision be solved, without significantly impeding one or the other?" They find that the retina is optimized to solve this problem:

[H]uman Müller cells separate white light according to its wavelengths; medium- and long-wavelength light is concentrated onto cones and short-wavelength light leaks to illuminate nearby rods. Next, we show similar theoretical calculations for the guinea pig Müller cells and describe imaging experiments in the isolated guinea pig retina, to find remarkable agreement between the experimental results and the computational model. These findings are consistent with the hypothesis that the wave guiding properties of Müller cells are wavelength-dependent in a manner that improves cone-mediated vision while minimally impeding rod-mediated vision.

The paper explains that Müller cells give the retina a specialized architecture to foster light collection: "We could clearly identify distinct light guiding tubes across most of the retinal depth, spanning the retina from the retinal surface down to just above the photoreceptors. The only retinal structures that fit these light-guiding tubes are the Müller cells." They conclude:

The findings presented here indicate that the spectral separation of light by Müller cells provides a mechanism to improve cone-mediated day vision, with minimal interference with rod-mediated night vision. This is achieved by wavelength sorting of incident light by the Müller cells. Light of relevant wavelengths for cone visual pigments is directed towards the cones, while light of wavelengths more suitable for rod vision is allowed to leak outside the Müller cells towards the surrounding rods. This is a novel mechanism that needs to be considered when visual phenomena concerning cone- and rod-mediated vision are analysed.

The implications of these findings have not been lost on expert optics commentators. A striking article at Phys.org about this new paper, "Fiber optic light pipes in the retina do much more than simple image transfer," reflects a keen awareness of the debate over whether the vertebrate eye is suboptimally designed. It concludes that the retinal architecture, as it now stands revealed, settles the debate. In the words of Phys.org, the notion that the vertebrate eye is suboptimally wired "is folly." Why? Because "Having the photoreceptors at the back of the retina is not a design constraint, it is a design feature." Here's the full passage from the article:

Having the photoreceptors at the back of the retina is not a design constraint, it is a design feature. The idea that the vertebrate eye, like a traditional front-illuminated camera, might have been improved somehow if it had only been able to orient its wiring behind the photoreceptor layer, like a cephalopod, is folly. Indeed in simply engineered systems, like CMOS or CCD image sensors, a back-illuminated design manufactured by flipping the silicon wafer and thinning it so that light hits the photocathode without having to navigate the wiring layer can improve photon capture across a wide wavelength band. But real eyes are much more crafty than that. A case in point are the Müller glia cells that span the thickness of the retina. These high refractive index cells spread an absorptive canopy across the retinal surface and then shepherd photons through a low-scattering cytoplasm to separate receivers, much like coins through a change sorting machine. A new paper in Nature Communications describes how these wavelength-dependent wave-guides can shuttle green-red light to cones while passing the blue-purples to adjacent rods. The idea that these Müller cells act as living fiber optic cables has been floated previously. It has even been convincingly demonstrated using a dual beam laser trap. In THIS case (THIS, like in Java programming meaning the paper just brought up) the authors couched this feat as mere image transfer, with the goal just being to bring light in with minimal distortion. (Emphasis added.)

Take special note of the sentences I've put in bold at the end of the last paragraph. These recent discoveries about the retina were made by proposing that Müller cells behave like "living fiber optic cables" that have a "goal" to "bring light in with minimal distortion." This is an example of systems-biology-thinking, as I described it here recently, where you assume that biological systems function much like goal-directed technology, and then reverse engineer a system to determine how it works. Such teleological thinking is once again bearing fruit in biology.

But the Phys.org article explains that these Müller cells aren't just passive cables that transfer images -- they are dynamic structures that can adjust to the amount of incoming light to avoid distorting the image:

In considering not just the classical photoreceptors but the entire retina itself as a light-harvesting engine, it seems prudent to also regard its entire synaptic endowment as a molecular-scale computing volume. In other words, when you have many cells that have no axons or spikes to speak of, that can completely refigure their fine structure within a few minutes to handle changing light levels, every synapse appears as an essential machine that percolates information as if at the Brownian scale, or even below. [...]
Most incredibly, like the wings of a swallow, the retina more-or-less works right out of the box, even if it has not seen any exercise. In seeking to understand how it then further refines its delicate structure we should perhaps not overlook the pervasive organizing influence of the incoming photons themselves. Now that it is becoming abundantly clear that the whole works can "feel" them, the next question to answer is how.

A Darwinian paradigm assumes that biological systems are cobbled together haphazardly by natural selection over eons of unguided descent with modification. Compare that paradigm with one that recognizes intelligent design and that accordingly predicts biological systems are built from the top down. In investigating the evidence of biology, ID expects to find goal-directed structures that are organized much like human technology -- except better, it often seems. Which model seems the more appropriate here?

 

Victors not victims.

Auschwitz Survivors Mark 70th Anniversary of Liberation, Jehovah’s Witnesses Among Those Remembered

WARSAW, Poland—On January 27, 2015, thousands will commemorate the 70th anniversary of the liberation of Auschwitz, a Nazi German concentration and death camp. This infamous camp, primarily used to eliminate racial groups targeted by the Nazis, was also a mechanism for persecuting Jehovah’s Witnesses of various nationalities, including Germans.

The Auschwitz-Birkenau State Museum and the International Auschwitz Council are organizing the event. The president of Poland, Bronisław Komorowski, is expected to attend, and several countries from around the world will send official state delegations. The event will also be broadcast live online.

Auschwitz is located in the suburbs of Oświęcim, a Polish city annexed by the Nazis during World War II. It began as a German concentration camp with some 700 Polish prisoners arriving there in June 1940. Auschwitz quickly grew into a massive complex with over 40 camps and subcamps. The four gas chambers in Auschwitz-Birkenau claimed as many as 20,000 lives a day. At least 1.1 million people, including over 400 Jehovah’s Witnesses, were sent to Auschwitz during its almost five years of operation.

According to the Auschwitz-Birkenau State Museum website: “Aside from brief mentions, the literature on the history of Auschwitz Concentration Camp does not take account of the Jehovah’s Witnesses (referred to in the camp records as Bible [Students]) who were imprisoned because of their religious convictions. These prisoners deserve closer attention because of the way they managed to hold on to their moral principles under camp conditions.” Museum records indicate that Jehovah’s Witnesses were among the first prisoners sent to Auschwitz, and of the hundreds of Witnesses sent, over 35 percent died there.

Andrzej Szalbot (Prisoner–IBV 108703): In 1943, arrested by Nazis and sent to Auschwitz for conscientiously objecting to military service.

The Nazi government targeted the activity of Jehovah’s Witnesses as early as 1933 and banned the organization throughout Germany. The Witnesses’ moral principles and practices were not compatible with Nazi ideology. For example, the Witnesses would not offer the obligatory “Heil Hitler!,” as they considered paying homage to Hitler a betrayal of their loyalty to God. The Witnesses also refused to perform any military-related duties, a stand the regime considered to be anti-state. “To refuse military service meant being sent to a concentration camp,” explains Andrzej Szalbot, who was arrested in 1943 and sent to Auschwitz at only 19 years of age. Jehovah’s Witnesses were promised immediate freedom if they signed a document renouncing their membership in the organization and declaring that its teachings were erroneous. Mr. Szalbot refused to sign.

Jehovah’s Witnesses were promised release if they renounced their faith by signing a declaration similar to this one.

Official Nazi documentation refers to Jehovah’s Witnesses by using the abbreviation “IBV,” which stood for Internationale Bibelforscher-Vereinigung (International Bible Students Association), the official German name of their organization. The Nazis required the Witnesses to wear a purple triangle on their uniforms. This symbol helped the Witnesses to identify their fellow believers in the camp. They met every evening before roll call for mutual support. Secret meetings were also organized to discuss the Bible with prisoners who were impressed by the Witnesses’ kindness and faith. A number of prisoners became Jehovah’s Witnesses while in Auschwitz camps.

On Saturday morning, January 27, 1945, the Soviet Union’s Red Army arrived in Oświęcim. By 3 p.m., the Soviet forces had liberated some 7,000 prisoners from Auschwitz I, Auschwitz II (Birkenau), and Auschwitz III (Monowitz).

Stanisław Zając. Arrived in Auschwitz on February 16, 1943.

Stanisław Zając, one of Jehovah’s Witnesses, was among the tens of thousands forced by the Nazis to evacuate the Auschwitz camps in anticipation of the Red Army’s approach. Mr. Zając and about 3,200 other prisoners left the Jaworzno subcamp and trudged through deep snow as part of the infamous death march. It is estimated that less than 2,000 survived the three-day walk to Blechhammer, an outlying Auschwitz subcamp located in the forest. In his memoirs, Mr. Zając recalled the battle that ensued while he and other prisoners were hiding in the camp: “We could hear tanks passing by, but nobody got up the courage to go and see to whom they belonged. In the morning, it turned out they were Russian. . . . The Russian army was filling the wide clearing and this is where my concentration camp nightmare ended.”

This year, on January 27, conferences and exhibitions related to the 70th anniversary of the liberation of Auschwitz will take place in various cities around the world.

Household maintenance makes no sense in the light of Darwinism.

How Many Darwinists Does it Take to Screw in a Light Bulb? Evolutionists and Intelligent Design Scientists Weigh in

Jonathan Witt 

A furious debate is stirring over at Cartago Delenda Est. The issue? How many Darwinists does it take to screw in a light bulb?

Charles Darwin: None. But if it could be shown that the bulb entered the socket without a series of clockwise turns, my theory would absolutely break down.

ACLU: None! We have separation of church and state in this country.

Eugenie Scott: None. To say a Darwinist did it is not a scientific explanation.

Panda's Thumb: None. To say that light bulbs don't screw themselves in is not a testable proposition. You can't prove they don't. That would be an argument from incredulity. You are committing a 'Darwinist Of The Gaps' fallacy.

Generic 2: None. The quintessentially non-random process of natural selection is sufficient. Those objects capable of giving off light when screwed into sockets will be in sockets. Those that aren't will be in the trash.

Richard Dawkins: None. A light bulb that gives off 1% light intensity is very much worth having. A bulb sitting on the shelf at the supermarket gives off a certain amount of light. One in the cupboard at home gives off more. One five feet from the socket gives off more, and one two feet away even more. One in the socket gives off the most of all. It is therefore inevitable that the bulb will reach the socket.

Stephen J. Gould: None. The bulb jumped into the socket when no one was looking. Gradually.

The complete and completely silly debate with opinions from "Kenneth Miller," "The Flying Spaghetti Monster," "Michael Ruse," and several design theorists

Bug-brained indeed!

How Much Brain Can You Pack Into a Spider Head?

Evolution News & Views April 23, 2015 2:58 PM | 

Thirty years ago, state-of-the-art "minicomputers" (as they were then called) were refrigerator-size contraptions loaded with large, flat circuit boards, heavy cables, and noisy fans. Disk drives the size of washing machines spun stacks of large metal plates for a grand total of 300 megabytes of storage. If a minicomputer bore unquestionable evidence of advanced intelligent design just a few years ago, how much more so a modern smartphone (now a smartwatch) with more processing power, and one hundred times the memory, in a thousandth of the space?

Well, now consider the lowly spider. Its entire brain is about the size of a pinhead. Yet this creature can dance! Here is a video of Maratus volans, the "peacock spider" of Australia -- this little guy is a beautyNo wonder the folks at Brain Decoder call this a "great mystery in a tiny head." Sara Goudarzi writes:

The spider may be itsy bitsy but its brain is nothing short of amazing. With just a poppy-seed-sized noggin, these arthropods employsophisticated hunting methods, can find their way out of complicated labyrinths, and some have mating dance moves that take the breath away from their fellow spiders. [Emphasis added.]

The elaborate decorations on the male's abdomens come in bright fluorescent colors, with patterns that look like human faces and other artistic designs -- yet the whole spider is only about five millimeters long! Still more amazing is the central nervous system that allows the male to raise and shake its colorful banner on command, and raise its third legs, in a complex mating display that may last almost an hour.

Mating is just one behavior controlled by a spider's brain. There are many others: engaging all its senses, knowing how to hunt and find food, knowing how to operate its eight legs in a coordinated way -- in fact, many of the behaviors larger animals need to survive and reproduce. Goudarzi focuses on one brain power in particular:

Another amazing feature of some spiders is their sophisticated visual systems. Jumping spiders, for example, have eight eyes, giving them a nearly 360 degree panoramic view, with two front-facing eyes that are as acute as human eyes. The visual combo allows these hunters to pursue and pounce on prey, much like cats do. But an interesting question for scientists is how the spider brain actually processes the visual information.

"As acute as human eyes"... the tiny camera lenses in today's smartphones, allowing them to take pictures almost as sharp as SLRs, come to mind.

We joke about teachers or parents with eyes in the back of their heads, but imagine actually having to operate eight eyes without getting confused. That's a lot of processing power in a poppy-seed brain, especially when you consider how fast these creatures can move. While dancing, the male is alert to the female's advances, and can retreat backwards as fast as her forward attack, if she doesn't like the dance. These motions are all controlled by fast-firing neurons in the spider's brain.

To be able to do such fine mental tasks, spiders need an elaborate nervous system. But they don't have much space in their tiny bodiesand there's a limit to how small neurons can get and still function.

Part of the solution is that the nervous system extends into the legs: "the central nervous systems of the smallest spiders fill up almost 80 percent of their total body cavity, including about a quarter of the space inside their legs."

Adding to the wonder, think about their webs. Orb-spinning spiders construct beautiful geometric webs out of one of the most perfect materials in nature -- a substance that is the envy of engineers for its strength and flexibility. Spiders can manipulate the strength of each strand, and make them sticky or plain. They maneuver deftly about their webs without getting stuck themselves, and use their legs to wrap their prey quickly while simultaneously secreting a specialized web material for that purpose.

Goudarzi writes about new techniques to get inside a spider's brain. It's delicate work, because the tissue is so tightly packed it tends to explode when punctured. Cornell biologist Ronald Hoy is one of the first to get a look inside a live spider's head with a tiny electrode. He finds that the organization of the spider brain is similar to any other brain:

"If you look at a section of spider brain you'll find that there areclusters of cell bodies with a cabling of the axons going from one part to another part and that's true of insects and that's true of us too," Hoy says. "Things are just more compact in a spider's brainbecause you're packing a normal head brain into the thoracic ganglion."

There are more than 44,500 identified species of spiders, Goudarzi says, and probably "at least as many yet to be discovered." National Geographic assures us that the vast majority are not venomous. The variety is staggering: orb weavers, jumpers, wolf spiders, tarantulas, trap-door spiders, water spiders at the bottom of the sea, and spiders that are hairy, smooth, black, white, or multicolored. Some can change color to match their backgrounds (PhysOrg). Not long ago, the biggest web weaver of all was discovered in Madagascar, able to build orb webs eighty feet wide that can span rivers (Daily Mail). (Shelob, call your office.)

Most spiders, however, are small enough to fit on a finger. The thought of a spider on your finger will creep some people out, but it's time to teach children to respect these small wonders and learn more about them. Before you step on that spider running across the floor, think about the high-tech brain you're squashing. You wouldn't do that to an Apple Watch, would you?:

closer and closer to the chasm?

Chinese scientists genetically modify human embryos

In a world first, Chinese scientists have reported editing the genomes of human embryos. The results are published¹ in the online journal Protein & Cell and confirm widespread rumours that such experiments had been conducted — rumours that sparked a high-profile debate last month^2, 3 about the ethical implications of such work.

In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off such concerns by using 'non-viable' embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications.

"I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale," says George Daley, a stem-cell biologist at Harvard Medical School in Boston, Massachusetts. "Their study should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes."

Related stories

• Mini enzyme moves gene editing closer to the clinic
• Ethics of embryo editing divides scientists
• Don’t edit the human germ line

Some say that gene editing in embryos could have a bright future because it could eradicate devastating genetic diseases before a baby is born. Others say that such work crosses an ethical line: researchers warned in Nature² in March that because the genetic changes to embryos, known as germline modification, are heritable, they could have an unpredictable effect on future generations. Researchers have also expressed concerns that any gene-editing research on human embryos could be a slippery slope towards unsafe or unethical uses of the technique.

The paper by Huang's team looks set to reignite the debate on human-embryo editing — and there are reports that other groups in China are also experimenting on human embryos.

Problematic gene

The technique used by Huang’s team involves injecting embryos with the enzyme complex CRISPR/Cas9, which binds and splices DNA at specific locations. The complex can be programmed to target a problematic gene, which is then replaced or repaired by another molecule introduced at the same time. The system is well studied in human adult cells and in animal embryos. But there had been no published reports of its use in human embryos.

Huang and his colleagues set out to see if the procedure could replace a gene in a single-cell fertilized human embryo; in principle, all cells produced as the embryo developed would then have the repaired gene. The embryos they obtained from the fertility clinics had been created for use in in vitro fertilization but had an extra set of chromosomes, following fertilization by two sperm. This prevents the embryos from resulting in a live birth, though they do undergo the first stages of development.

Huang’s group studied the ability of the CRISPR/Cas9 system to edit the gene called HBB, which encodes the human β-globin protein. Mutations in the gene are responsible for β-thalassaemia.

Serious obstacles

The team injected 86 embryos and then waited 48 hours, enough time for the CRISPR/Cas9 system and the molecules that replace the missing DNA to act — and for the embryos to grow to about eight cells each. Of the 71 embryos that survived, 54 were genetically tested. This revealed that just 28 were successfully spliced, and that only a fraction of those contained the replacement genetic material. “If you want to do it in normal embryos, you need to be close to 100%,” Huang says. “That’s why we stopped. We still think it’s too immature.”

His team also found a surprising number of ‘off-target’ mutations assumed to be introduced by the CRISPR/Cas9 complex acting on other parts of the genome. This effect is one of the main safety concerns surrounding germline gene editing because these unintended mutations could be harmful. The rates of such mutations were much higher than those observed in gene-editing studies of mouse embryos or human adult cells. And Huang notes that his team likely only detected a subset of the unintended mutations because their study looked only at a portion of the genome, known as the exome. “If we did the whole genome sequence, we would get many more,” he says.

Ethical questions

Huang says that the paper was rejected by Nature and Science, in part because of ethical objections; both journals declined to comment on the claim. (Nature’s news team is editorially independent of its research editorial team.)

He adds that critics of the paper have noted that the low efficiencies and high number of off-target mutations could be specific to the abnormal embryos used in the study. Huang acknowledges the critique, but because there are no examples of gene editing in normal embryos he says that there is no way to know if the technique operates differently in them.

Still, he maintains that the embryos allow for a more meaningful model — and one closer to a normal human embryo — than an animal model or one using adult human cells. “We wanted to show our data to the world so people know what really happened with this model, rather than just talking about what would happen without data,” he says.

But Edward Lanphier, one of the scientists who sounded the warning in Nature last month, says: "It underlines what we said before: we need to pause this research and make sure we have a broad based discussion about which direction we’re going here." Lanphier is president of Sangamo BioSciences in Richmond, California, which applies gene-editing techniques to adult human cells.

Huang now plans to work out how to decrease the number of off-target mutations using adult human cells or animal models. He is considering different strategies — tweaking the enzymes to guide them more precisely to the desired spot, introducing the enzymes in a different format that could help to regulate their lifespans and thus allow them to be shut down before mutations accumulate, or varying the concentrations of the introduced enzymes and repair molecules. He says that using other gene-editing techniques might also help. CRISPR/Cas9 is relatively efficient and easy to use, but another system called TALEN is known to cause fewer unintended mutations.

The debate over human embryo editing is sure to continue for some time, however. CRISPR/Cas9 is known for its ease of use and Lanphier fears that more scientists will now start to work towards improving on Huang's paper. “The ubiquitous access to and simplicity of creating CRISPRs," he says, "creates opportunities for scientists in any part of the world to do any kind of experiments they want.”

A Chinese source familiar with developments in the field said that at least four groups in China are pursuing gene editing in human embryos.