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Sunday, June 28, 2015

Evolution of birds


From Wikipedia, the free encyclopedia


The evolution of birds is thought to have begun in the Jurassic Period, with the earliest birds derived from a clade of theropoda dinosaurs named Paraves. Birds are categorized as a biological class, Aves. The earliest known is Archaeopteryx lithographica, from the Late Jurassic period, though Archaeopteryx is not commonly considered to have been a true bird. Modern phylogenies place birds in the dinosaur clade Theropoda. According to the current consensus, Aves and a sister group, the order Crocodilia, together are the sole living members of an unranked "reptile" clade, the Archosauria.

Phylogenetically, Aves is usually defined as all descendants of the most recent common ancestor of a specific modern bird species (such as the house sparrow, Passer domesticus), and either Archaeopteryx,[1] or some prehistoric species closer to Neornithes (to avoid the problems caused by the unclear relationships of Archaeopteryx to other theropods).[2] If the latter classification is used then the larger group is termed Avialae. Currently, the relationship between dinosaurs, Archaeopteryx, and modern birds is still under debate.

Origins


The mounted skeleton of a Velociraptor, showing the very bird-like quality of the smaller theropod dinosaurs

There is significant evidence that birds emerged within theropod dinosaurs, specifically, that birds are members of Maniraptora, a group of theropods which includes dromaeosaurs and oviraptorids, among others.[3] As more non-avian theropods that are closely related to birds are discovered, the formerly clear distinction between non-birds and birds becomes less so. This was noted already in the 19th century, with Thomas Huxley writing:
We have had to stretch the definition of the class of birds so as to include birds with teeth and birds with paw-like fore limbs and long tails. There is no evidence that Compsognathus possessed feathers; but, if it did, it would be hard indeed to say whether it should be called a reptilian bird or an avian reptile.[4]
Discoveries in northeast China (Liaoning Province) demonstrate that many small theropod dinosaurs did indeed have feathers, among them the compsognathid Sinosauropteryx and the microraptorian dromaeosaurid Sinornithosaurus. This has contributed to this ambiguity of where to draw the line between birds and reptiles.[5]  
Cryptovolans, a dromaeosaurid found in 2002 (which may be a junior synonym of Microraptor) was capable of powered flight, possessed a sternal keel and had ribs with uncinate processes. Cryptovolans seems to make a better "bird" than Archaeopteryx which lacks some of these modern bird features. Because of this, some paleontologists have suggested that dromaeosaurs are actually basal birds whose larger members are secondarily flightless, i.e. that dromaeosaurs evolved from birds and not the other way around. Evidence for this theory is currently inconclusive, but digs continue to unearth fossils (especially in China) of feathered dromaeosaurs. At any rate, it is fairly certain that flight utilizing feathered wings existed in the mid-Jurassic theropods. The Cretaceous unenlagiine Rahonavis also possesses features suggesting it was at least partially capable of powered flight.

Although ornithischian (bird-hipped) dinosaurs share the same hip structure as birds, birds actually originated from the saurischian (lizard-hipped) dinosaurs if the dinosaurian origin theory is correct. They thus arrived at their hip structure condition independently. In fact, a bird-like hip structure also developed a third time among a peculiar group of theropods, the Therizinosauridae.

An alternate theory to the dinosaurian origin of birds, espoused by a few scientists, notably Larry Martin and Alan Feduccia, states that birds (including maniraptoran "dinosaurs") evolved from early archosaurs like Longisquama.[6] This theory is contested by most other paleontologists and experts in feather development and evolution.[7]

Mesozoic birds


Reconstruction of Iberomesornis romerali, a toothed enantiornithe

The basal bird Archaeopteryx, from the Jurassic, is well known as one of the first "missing links" to be found in support of evolution in the late 19th century. Though it is not considered a direct ancestor of modern birds, it gives a fair representation of how flight evolved and how the very first bird might have looked. It may be predated by Protoavis texensis, though the fragmentary nature of this fossil leaves it open to considerable doubt whether this was a bird ancestor. The skeleton of all early bird candidates is basically that of a small theropod dinosaur with long, clawed hands, though the exquisite preservation of the Solnhofen Plattenkalk shows Archaeopteryx was covered in feathers and had wings.[4] While Archaeopteryx and its relatives may not have been very good fliers, they would at least have been competent gliders, setting the stage for the evolution of life on the wing.

The evolutionary trend among birds has been the reduction of anatomical elements to save weight. The first element to disappear was the bony tail, being reduced to a pygostyle and the tail function taken over by feathers. Confuciusornis is an example of their trend. While keeping the clawed fingers, perhaps for climbing, it had a pygostyle tail, though longer than in modern birds. A large group of birds, the Enantiornithes, evolved into ecological niches similar to those of modern birds and flourished throughout the Mesozoic. Though their wings resembled those of many modern bird groups, they retained the clawed wings and a snout with teeth rather than a beak in most forms. The loss of a long tail was followed by a rapid evolution of their legs which evolved to become highly versatile and adaptable tools that opened up new ecological niches.[8]

The Cretaceous saw the rise of more modern birds with a more rigid ribcage with a carina and shoulders able to allow for a powerful upstroke, essential to sustained powered flight. Another improvement was the appearance of an alula, used to achieve better control of landing or flight at low speeds. They also had a more derived pygostyle, with a ploughshare-shaped end. An early example is Yanornis. Many were coastal birds, strikingly resembling modern shorebirds, like Ichthyornis, or ducks, like Gansus. Some evolved as swimming hunters, like the Hesperornithiformes – a group of flightless divers resembling grebes and loons. While modern in most respects, most of these birds retained typical reptilian-like teeth and sharp claws on the manus.

The modern toothless birds evolved from the toothed forefathers in the Cretaceous.[9] While the earlier primitive birds, particularly the Enantiornithes, continued to thrive and diversify alongside the pterosaurs, all but a few groups of the toothless Neornithes were cut short at the Chicxulub impact. The surviving lineages of birds were the comparatively primitive Paleognathae (ostrich and its allies), the aquatic duck lineage, the terrestrial fowl, and the highly volant Neoaves.

Adaptive radiation of modern birds


Haast's eagle and New Zealand moa, the eagle is a Neognath, the moas are Paleognaths.

Modern birds are classified in Neornithes, which are now known to have evolved into some basic lineages by the end of the Cretaceous (see Vegavis). The Neornithes are split into the paleognaths and neognaths.

The paleognaths include the tinamous (found only in Central and South America) and the ratites, which nowadays are found almost exclusively on the Southern Hemisphere. The ratites are large flightless birds, and include ostriches, rheas, cassowaries, kiwis and emus. A few scientists propose that the ratites represent an artificial grouping of birds which have independently lost the ability to fly in a number of unrelated lineages.[10] In any case, the available data regarding their evolution is still very confusing, partly because there are no uncontroversial fossils from the Mesozoic.

The basal divergence from the remaining Neognathes was that of the Galloanserae, the superorder containing the Anseriformes (ducks, geese and swans), and the Galliformes (chickens, turkeys, pheasants, and their allies). The presence of basal anseriform fossils in the Mesozoic and likely some galliform fossils implies the presence of paleognaths at the same time, in spite of the absence of fossil evidence.

The dates for the splits are a matter of considerable debate amongst scientists. It is agreed that the Neornithes evolved in the Cretaceous and that the split between the Galloanserae and the other neognaths - the Neoaves - occurred before the Cretaceous–Paleogene extinction event, but there are different opinions about whether the radiation of the remaining neognaths occurred before or after the extinction of the other dinosaurs.[11] This disagreement is in part caused by a divergence in the evidence, with molecular dating suggesting a Cretaceous radiation, a small and equivocal neoavian fossil record from Cretaceous, and most living families turning up during the Paleogene. Attempts made to reconcile the molecular and fossil evidence have proved controversial.[11][12]

On the other hand, two factors must be considered: First, molecular clocks cannot be considered reliable in the absence of robust fossil calibration, whereas the fossil record is naturally incomplete. Second, in reconstructed phylogenetic trees, the time and pattern of lineage separation corresponds to the evolution of the characters (such as DNA sequences, morphological traits etc.) studied, not to the actual evolutionary pattern of the lineages; these ideally should not differ by much, but may well do so in practice.

Considering this, it is easy to see that fossil data, compared to molecular data, tends to be more accurate in general, but also to underestimate divergence times: morphological traits, being the product of entire developmental genetics networks, usually only start to diverge some time after a lineage split would become apparent in DNA sequence comparison - especially if the sequences used contain many silent mutations.

Classification of modern species


The diversity of modern birds

The phylogenetic classification of birds is a contentious issue. Sibley & Ahlquist's Phylogeny and Classification of Birds (1990) is a landmark work on the classification of birds (although frequently debated and constantly revised).
A preponderance of evidence suggests that most modern bird orders constitute good clades. However, scientists are not in agreement as to the precise relationships between the main clades. Evidence from modern bird anatomy, fossils and DNA have all been brought to bear on the problem but no strong consensus has emerged. As of the mid-2000s, new fossil and molecular data provide an increasingly clear picture of the evolution of modern bird orders, and their relationships. For example, the Charadriiformes seem to constitute an ancient and distinct lineage, while the Mirandornithes and Cypselomorphae are supported by a wealth of anatomical and molecular evidence.
The understanding of the interrelationships of lower level taxa also continues to increase, particularly in the massively diverse perching bird group Passeriformes.

Bird classification and phylogenetic analysis is still under debate and requires more research. A 2008 study published in Science examined DNA sequences from 169 species of birds that represented all of the major extant groups. The findings may necessitate a wholesale restructuring of the avian phylogenetic tree. The findings also supported unestablished relationships between orders and confirmed disputes over particular groupings.[13]

Current evolutionary trends in birds

Evolution generally occurs at a scale far too slow to be witnessed by humans. However, bird species are currently going extinct at a far greater rate than any possible speciation or other generation of new species. The disappearance of a population, subspecies, or species represents the permanent loss of a range of genes.
Another concern with evolutionary implications is a suspected increase in hybridization. This may arise from human alteration of habitats enabling related allopatric species to overlap. Forest fragmentation can create extensive open areas, connecting previously isolated patches of open habitat. Populations that were isolated for sufficient time to diverge significantly, but not sufficient to be incapable of producing fertile offspring may now be interbreeding so broadly that the integrity of the original species may be compromised. For example, the many hybrid hummingbirds found in northwest South America may represent a threat to the conservation of the distinct species involved.[14]

Several species of birds have been bred in captivity to create variations on wild species. In some birds this is limited to color variations, while others are bred for larger egg or meat production, for flightlessness or other characteristics.

Message from the Big Bang --"Confirms Quantum Origin of the Universe"

Data collected by Planck telescope have confirmed beyond any logical uncertainty a theory of the quantum origin of structure in the Cosmos. What precisely occurred after the Universe was born? Why did stars, planets and gigantic galaxies appear? These are the problems that cover Viatcheslav Mukhanov, a cosmologist at Ludwig-Maximilians-Universitaet (LMU) in Munich is a professional in the Theoretical Cosmology. He has used the idea of so-called quantum variations to make a theory that offers a exact picture of the vital early stage of the evolution of our Universe: Without the slight variations in energy density that result from the minute but inevitable quantum fluctuations, one cannot account for the creation of stars, planets and galaxies that illustrate the Universe we witness today. The Planck Consortium has now issued new survey of data resumed by the Planck Space Telescope that has measured the dispersal of the cosmic microwave background radiation (CMB), which, in principle, defines what the Universe looked like about 400,000 years after the Big Bang. These up-to-date results are in complete agreement with the forecasts of Mukhanov's theory - for instance, his calculation of the rate of the so-called spectral catalog of the initial inhomogeneities.
 
Image credit: Wikigag.com
The notion that quantum fluctuations must have played a part in the very initial stage of the history of the Cosmos is implied in Heisenberg's Uncertainty Principle, according to Mukhanov. 
Heisenberg presented that there is an exact boundary to the accuracy with which the position and the momentum of a particle can be resolute at any given moment. This in turn suggests that the early matter scattering will unavoidably show tiny inhomogeneities in density. Mukhanov's calculations first validated that such quantum fluctuations could give upsurge to density alterations in the early Universe, which in turn could assist as seeds for the galaxies and their clusters. Certainly, without quantum fluctuations, whose nature and magnitude Mukhanov quantitatively described, the detected dispersal of matter in the Universe would be bizarre.
In March 2014, a group of researchers informed the detection of the long-sought pattern. Though, doubts soon arose concerning this interpretation. Now a combined study by the Planck and BICEP2 teams has determined that the data do not truly provide observational proof for gravitational waves. In the spring of 2014 Mukhanov had already stated that, if the theory is right, then the BICEP2 and Planck teams could not both be correct.

Wednesday, June 24, 2015

Anti-intellectualism Is Killing America

dylann roof facebook
Source: dylann roof facebook

The tragedy in Charleston last week will no doubt lead to more discussion of several important and recurring issues in American culture—particularly racism and gun violence—but these dialogues are unlikely to bear much fruit until the nation undertakes a serious self-examination. Decrying racism and gun violence is fine, but for too long America’s social dysfunction has continued to intensify as the nation has ignored a key underlying pathology: anti-intellectualism.

America is killing itself through its embrace and exaltation of ignorance, and the evidence is all around us. Dylann Roof, the Charleston shooter who used race as a basis for hate and mass murder, is just the latest horrific example. Many will correctly blame Roof's actions on America's culture of racism and gun violence, but it's time to realize that such phenomena are directly tied to the nation's culture of ignorance.

In a country where a sitting congressman told a crowd that evolution and the Big Bang are “lies straight from the pit of hell,” (link is external) where the chairman of a Senate environmental panel brought a snowball (link is external) into the chamber as evidence that climate change is a hoax, where almost one in three citizens can’t name the vice president (link is external), it is beyond dispute that critical thinking has been abandoned as a cultural value. Our failure as a society to connect the dots, to see that such anti-intellectualism comes with a huge price, could eventually be our downfall.

In considering the senseless loss of nine lives in Charleston, of course racism jumps out as the main issue. But isn’t ignorance at the root of racism? And it’s true that the bloodshed is a reflection of America's violent, gun-crazed culture, but it is only our aversion to reason as a society that has allowed violence to define the culture. Rational public policy, including policies that allow reasonable restraints on gun access, simply isn't possible without an informed, engaged, and rationally thinking public.

Some will point out, correctly, that even educated people can still be racists, but this shouldn’t remove the spotlight from anti-intellectualism. Yes, even intelligent and educated individuals, often due to cultural and institutional influences, can sometimes carry racist biases. But critically thinking individuals recognize racism as wrong and undesirable, even if they aren’t yet able to eliminate every morsel of bias from their own psyches or from social institutions. An anti-intellectual society, however, will have large swaths of people who are motivated by fear, susceptible to tribalism and simplistic explanations, incapable of emotional maturity, and prone to violent solutions. Sound familiar?

And even though it may seem counter-intuitive, anti-intellectualism has little to do with intelligence. We know little about the raw intellectual abilities of Dylann Roof, but we do know that he is an ignorant racist who willfully allowed irrational hatred of an entire demographic to dictate his actions. Whatever his IQ, to some extent he is a product of a culture driven by fear and emotion, not rational thinking, and his actions reflect the paranoid mentality of one who fails to grasp basic notions of what it means to be human.

What Americans rarely acknowledge is that many of their social problems are rooted in the rejection of critical thinking or, conversely, the glorification of the emotional and irrational. What else could explain the hyper-patriotism (link is external) that has many accepting an outlandish notion that America is far superior to the rest of the world? Love of one’s country is fine, but many Americans seem to honestly believe that their country both invented and perfected the idea of freedom, that the quality of life here far surpasses everywhere else in the world.

But it doesn’t. International quality of life rankings (link is external) place America far from the top, at sixteenth. America’s rates of murder (link is external) and other violent crime dwarf most of the rest of the developed world, as does its incarceration rate (link is external), while its rates of education and scientific literacy are embarrassingly low (link is external). American schools, claiming to uphold “traditional values,” avoid fact-based sex education, and thus we have the highest rates of teen pregnancy (link is external) in the industrialized world. And those rates are notably highest where so-called “biblical values” are prominent. Go outside the Bible belt, and the rates generally trend downward (link is external).

As this suggests, the impact of fundamentalist religion in driving American anti-intellectualism has been, and continues to be, immense. Old-fashioned notions of sex education may seem like a relatively minor issue to many, but taking old-time religion too seriously can be extremely dangerous in the modern era. High-ranking individuals, even in the military (link is external), see a confrontation between good and evil as biblically predicted and therefore inevitable. They relish the thought of being a righteous part of the final days.

Fundamentalist religion is also a major force in denying human-caused climate change (link is external), a phenomenon that the scientific community has accepted for years. Interestingly, anti-intellectual fundamentalists are joined in their climate change denial with unusual bedfellows: corporate interests (link is external) that stand to gain from the rejection of sound science on climate.

Corporate influence on climate and environmental policy, meanwhile, is simply more evidence of anti-intellectualism in action, for corporate domination of American society is another result of a public that is not thinking critically. Americans have allowed their democracy to slip away, their culture overtaken by enormous corporations that effectively control both the governmental apparatus and the media, thus shaping life around materialism and consumption.

Indeed, these corporate interests encourage anti-intellectualism, conditioning Americans into conformity and passive acceptance of institutional dominance. They are the ones who stand to gain from the excessive fear and nationalism that result in militaristic foreign policy and absurdly high levels of military spending (link is external). They are the ones who stand to gain from consumers who spend money they don’t have on goods and services they don’t need. They are the ones who want a public that is largely uninformed and distracted, thus allowing government policy to be crafted by corporate lawyers and lobbyists. They are the ones who stand to gain from unregulated securities markets. And they are the ones who stand to gain from a prison-industrial complex that generates the highest rates of incarceration in the developed world.

Americans can and should denounce the racist and gun-crazed culture that shamefully resulted in nine corpses in Charleston this week, but they also need to dig deeper. At the core of all of this dysfunction is an abandonment of reason.

Published measurements of climate sensitivity declining

 https://landshape.files.wordpress.com/2015/06/climate_sensitivity5.png

Original link: https://landshape.wordpress.com/2015/06/20/6921/

The climate sensitivity due to CO2 is expressed as the temperature change in °C associated with a doubling of the concentration of carbon dioxide in Earth’s atmosphere. The equilibrium climate sensitivity (ECS) refers to the equilibrium change in global mean near-surface air temperature that would result from a sustained doubling of the atmospheric carbon dioxide concentration.  The transient climate response (TCR) is defined as the average temperature response over a twenty-year period centered at CO2 doubling in a transient simulation with CO2 increasing at 1% per year. The transient response is lower than the equilibrium sensitivity, due to the “inertia” of ocean heat uptake.

Scientists made numerous estimates of climate sensitivity over the last few decades and have yet to determine the correct value.  The figure shows the change in published climate sensitivity measurements over the past 15 years (from here).  The ECS and TCR estimates have both declined in the last 15 years, with the ECS declining from 6C to less than 2C.  While one cannot extrapolate from past results, it is likely that the true figure is below 2C, and may continue to decline.  Based on this historic pattern we should reject the studies that falsely exaggerated the climate sensitivity in the past and remember that global warming is not the most serious issue facing the world today.

Monday, June 22, 2015

The Climate Wars’ Damage to Science

The great thing about science is that it’s self-correcting. The good drives out the bad, because experiments get replicated and hypotheses tested -- or so I used to think. Now, thanks largely to climate science, I see bad ideas can persist for decades, and surrounded by myrmidons of furious defenders they become intolerant dogmas.

For much of my life I have been a science writer. That means I eavesdrop on what’s going on in laboratories so I can tell interesting stories. It’s analogous to the way art critics write about art, but with a difference: we “science critics” rarely criticise. If we think a scientific paper is dumb, we just ignore it. There’s too much good stuff coming out of science to waste time knocking the bad stuff.

Sure, we occasionally take a swipe at pseudoscience—homeopathy, astrology, claims that genetically modified food causes cancer, and so on. But the great thing about science is that it’s self-correcting. The good drives out the bad, because experiments get replicated and hypotheses put to the test. So a really bad idea cannot survive long in science.

Or so I used to think. Now, thanks largely to climate science, I have changed my mind. It turns out bad ideas can persist in science for decades, and surrounded by myrmidons of furious defenders they can turn into intolerant dogmas.

This should have been obvious to me. Lysenkoism, a pseudo-biological theory that plants (and people) could be trained to change their heritable natures, helped starve millions and yet persisted for decades in the Soviet Union, reaching its zenith under Nikita Khrushchev. The theory that dietary fat causes obesity and heart disease, based on a couple of terrible studies in the 1950s, became unchallenged orthodoxy and is only now fading slowly.

What these two ideas have in common is that they had political support, which enabled them to monopolise debate. Scientists are just as prone as anybody else to “confirmation bias”, the tendency we all have to seek evidence that supports our favoured hypothesis and dismiss evidence that contradicts it—as if we were counsel for the defence. It’s tosh that scientists always try to disprove their own theories, as they sometimes claim, and nor should they. But they do try to disprove each other’s. Science has always been decentralised, so Professor Smith challenges Professor Jones’s claims, and that’s what keeps science honest.

What went wrong with Lysenko and dietary fat was that in each case a monopoly was established. Lysenko’s opponents were imprisoned or killed. Nina Teicholz’s book The Big Fat Surprise shows in devastating detail how opponents of Ancel Keys’s dietary fat hypothesis were starved of grants and frozen out of the debate by an intolerant consensus backed by vested interests, echoed and amplified by a docile press.

Cheerleaders for alarm

This is precisely what has happened with the climate debate and it is at risk of damaging the whole reputation of science. The “bad idea” in this case is not that climate changes, nor that human beings influence climate change; but that the impending change is sufficiently dangerous to require urgent policy responses. In the 1970s, when global temperatures were cooling, some scientists could not resist the lure of press attention by arguing that a new ice age was imminent. Others called this nonsense and the World Meteorological Organisation rightly refused to endorse the alarm. That’s science working as it should. In the 1980s, as temperatures began to rise again, some of the same scientists dusted off the greenhouse effect and began to argue that runaway warming was now likely.

At first, the science establishment reacted sceptically and a diversity of views was aired. It’s hard to recall now just how much you were allowed to question the claims in those days. As Bernie Lewin reminds us in one chapter of a fascinating new book of essays called Climate Change: The Facts (hereafter The Facts), as late as 1995 when the second assessment report of the Intergovernmental Panel on Climate Change (IPCC) came out with its last-minute additional claim of a “discernible human influence” on climate, Nature magazine warned scientists against overheating the debate.

Since then, however, inch by inch, the huge green pressure groups have grown fat on a diet of constant but ever-changing alarm about the future. That these alarms—over population growth, pesticides, rain forests, acid rain, ozone holes, sperm counts, genetically modified crops—have often proved wildly exaggerated does not matter: the organisations that did the most exaggeration trousered the most money. In the case of climate, the alarm is always in the distant future, so can never be debunked.

These huge green multinationals, with budgets in the hundreds of millions of dollars, have now systematically infiltrated science, as well as industry and media, with the result that many high-profile climate scientists and the journalists who cover them have become one-sided cheerleaders for alarm, while a hit squad of increasingly vicious bloggers polices the debate to ensure that anybody who steps out of line is punished. They insist on stamping out all mention of the heresy that climate change might not be lethally dangerous.

Today’s climate science, as Ian Plimer points out in his chapter in The Facts, is based on a “pre-ordained conclusion, huge bodies of evidence are ignored and analytical procedures are treated as evidence”. Funds are not available to investigate alternative theories. Those who express even the mildest doubts about dangerous climate change are ostracised, accused of being in the pay of fossil-fuel interests or starved of funds; those who take money from green pressure groups and make wildly exaggerated statements are showered with rewards and treated by the media as neutral.

Look what happened to a butterfly ecologist named Camille Parmesan when she published a paper on “Climate and Species Range” that blamed climate change for threatening the Edith checkerspot butterfly with extinction in California by driving its range northward. The paper was cited more than 500 times, she was invited to speak at the White House and she was asked to contribute to the IPCC’s third assessment report.

Unfortunately, a distinguished ecologist called Jim Steele found fault with her conclusion: there had been more local extinctions in the southern part of the butterfly’s range due to urban development than in the north, so only the statistical averages moved north, not the butterflies. There was no correlated local change in temperature anyway, and the butterflies have since recovered throughout their range. When Steele asked Parmesan for her data, she refused. Parmesan’s paper continues to be cited as evidence of climate change. Steele meanwhile is derided as a “denier”. No wonder a highly sceptical ecologist I know is very reluctant to break cover.

Jim Hansen, recently retired as head of the Goddard Institute of Space Studies at NASA, won over a million dollars in lucrative green prizes, regularly joined protests against coal plants and got himself arrested while at the same time he was in charge of adjusting and homogenising one of the supposedly objective data sets on global surface temperature. How would he be likely to react if told of evidence that climate change is not such a big problem?

Michael Oppenheimer, of Princeton University, who frequently testifies before Congress in favour of urgent action on climate change, was the Environmental Defense Fund’s senior scientist for nineteen years and continues to advise it. The EDF has assets of $209 million and since 2008 has had over $540 million from charitable foundations, plus $2.8 million in federal grants. In that time it has spent $11.3 million on lobbying, and has fifty-five people on thirty-two federal advisory committees. How likely is it that they or Oppenheimer would turn around and say global warming is not likely to be dangerous?

Why is it acceptable, asks the blogger Donna Laframboise, for the IPCC to “put a man who has spent his career cashing cheques from both the World Wildlife Fund (WWF) and Greenpeace in charge of its latest chapter on the world’s oceans?” She’s referring to the University of Queensland’s Ove Hoegh-Guldberg.

These scientists and their guardians of the flame repeatedly insist that there are only two ways of thinking about climate change—that it’s real, man-made and dangerous (the right way), or that it’s not happening (the wrong way). But this is a false dichotomy. There is a third possibility: that it’s real, partly man-made and not dangerous. This is the “lukewarmer” school, and I am happy to put myself in this category. Lukewarmers do not think dangerous climate change is impossible; but they think it is unlikely.

I find that very few people even know of this. Most ordinary people who do not follow climate debates assume that either it’s not happening or it’s dangerous. This suits those with vested interests in renewable energy, since it implies that the only way you would be against their boondoggles is if you “didn’t believe” in climate change.

What consensus about the future?

Sceptics such as Plimer often complain that “consensus” has no place in science. Strictly they are right, but I think it is a red herring. I happily agree that you can have some degree of scientific consensus about the past and the present. The earth is a sphere; evolution is true; carbon dioxide is a greenhouse gas. The IPCC claims in its most recent report that it is “95 per cent” sure that “more than half” of the (gentle) warming “since 1950” is man-made. I’ll drink to that, though it’s a pretty vague claim. But you really cannot have much of a consensus about the future. Scientists are terrible at making forecasts—indeed as Dan Gardner documents in his book Future Babble they are often worse than laymen. And the climate is a chaotic system with multiple influences of which human emissions are just one, which makes prediction even harder.

The IPCC actually admits the possibility of lukewarming within its consensus, because it gives a range of possible future temperatures: it thinks the world will be between about 1.5 and four degrees warmer on average by the end of the century. That’s a huge range, from marginally beneficial to terrifyingly harmful, so it is hardly a consensus of danger, and if you look at the “probability density functions” of climate sensitivity, they always cluster towards the lower end.

What is more, in the small print describing the assumptions of the “representative concentration pathways”, it admits that the top of the range will only be reached if sensitivity to carbon dioxide is high (which is doubtful); if world population growth re-accelerates (which is unlikely); if carbon dioxide absorption by the oceans slows down (which is improbable); and if the world economy goes in a very odd direction, giving up gas but increasing coal use tenfold (which is implausible).

But the commentators ignore all these caveats and babble on about warming of “up to” four degrees (or even more), then castigate as a “denier” anybody who says, as I do, the lower end of the scale looks much more likely given the actual data. This is a deliberate tactic. Following what the psychologist Philip Tetlock called the “psychology of taboo”, there has been a systematic and thorough campaign to rule out the middle ground as heretical: not just wrong, but mistaken, immoral and beyond the pale. That’s what the word denier with its deliberate connotations of Holocaust denial is intended to do. For reasons I do not fully understand, journalists have been shamefully happy to go along with this fundamentally religious project.

Politicians love this polarising because it means they can attack a straw man. It’s what they are good at. “Doubt has been eliminated,” said Gro Harlem Brundtland, former Prime Minister of Norway and UN Special Representative on Climate Change, in a speech in 2007: “It is irresponsible, reckless and deeply immoral to question the seriousness of the situation. The time for diagnosis is over. Now it is time to act.” John Kerry says we have no time for a meeting of the flat-earth society. Barack Obama says that 97 per cent of scientists agree that climate change is “real, man-made and dangerous”. That’s just a lie (or a very ignorant remark): as I point out above, there is no consensus that it’s dangerous.

So where’s the outrage from scientists at this presidential distortion? It’s worse than that, actually. The 97 per cent figure is derived from two pieces of pseudoscience that would have embarrassed a homeopath. The first was a poll that found that 97 per cent of just seventy-nine scientists thought climate change was man-made—not that it was dangerous. A more recent poll of 1854 members of the American Meteorological Society found the true number is 52 per cent.

The second source of the 97 per cent number was a survey of scientific papers, which has now been comprehensively demolished by Professor Richard Tol of Sussex University, who is probably the world’s leading climate economist. As the Australian blogger Joanne Nova summarised Tol’s findings, John Cook of the University of Queensland and his team used an unrepresentative sample, left out much useful data, used biased observers who disagreed with the authors of the papers they were classifying nearly two-thirds of the time, and collected and analysed the data in such a way as to allow the authors to adjust their preliminary conclusions as they went along, a scientific no-no if ever there was one. The data could not be replicated, and Cook himself threatened legal action to hide them. Yet neither the journal nor the university where Cook works has retracted the paper, and the scientific establishment refuses to stop citing it, let alone blow the whistle on it. Its conclusion is too useful.

This should be a huge scandal, not fodder for a tweet by the leader of the free world. Joanne Nova, incidentally, is an example of a new breed of science critic that the climate debate has spawned. With little backing, and facing ostracism for her heresy, this talented science journalist had abandoned any chance of a normal, lucrative career and systematically set out to expose the way the huge financial gravy train that is climate science has distorted the methods of science. In her chapter in The Facts, Nova points out that the entire trillion-dollar industry of climate change policy rests on a single hypothetical assumption, first advanced in 1896, for which to this day there is no evidence.

The assumption is that modest warming from carbon dioxide must be trebly amplified by extra water vapour—that as the air warms there will be an increase in absolute humidity providing “a positive feedback”. That assumption led to specific predictions that could be tested. And the tests come back negative again and again. The large positive feedback that can turn a mild warming into a dangerous one just is not there. There is no tropical troposphere hot-spot. Ice cores unambiguously show that temperature can fall while carbon dioxide stays high. Estimates of climate sensitivity, which should be high if positive feedbacks are strong, are instead getting lower and lower. Above all, the temperature has failed to rise as predicted by the models.

Scandal after scandal

The Cook paper is one of many scandals and blunders in climate science. There was the occasion in 2012 when the climate scientist Peter Gleick stole the identity of a member of the (sceptical) Heartland Institute’s board of directors, leaked confidential documents, and included also a “strategy memo” purporting to describe Heartland’s plans, which was a straight forgery. Gleick apologised but continues to be a respected climate scientist.

There was Stephan Lewandowsky, then at the University of Western Australia, who published a paper titled “NASA faked the moon landing therefore [climate] science is a hoax”, from which readers might have deduced, in the words of a Guardian headline, that “new research finds that sceptics also tend to support conspiracy theories such as the moon landing being faked”. Yet in fact in the survey for the paper, only ten respondents out of 1145 thought that the moon landing was a hoax, and seven of those did not think climate change was a hoax. A particular irony here is that two of the men who have actually been to the moon are vocal climate sceptics: Harrison Schmitt and Buzz Aldrin.

It took years of persistence before physicist Jonathan Jones and political scientist Ruth Dixon even managed to get into print (in March this year) a detailed and devastating critique of the Lewandowsky article’s methodological flaws and bizarre reasoning, with one journal allowing Lewandowsky himself to oppose the publication of their riposte. Lewandowsky published a later paper claiming that the reactions to his previous paper proved he was right, but it was so flawed it had to be retracted.

If these examples of odd scientific practice sound too obscure, try Rajendra Pachauri, chairman of the IPCC for thirteen years and often described as the “world’s top climate scientist”. He once dismissed as “voodoo science” an official report by India’s leading glaciologist, Vijay Raina, because it had challenged a bizarre claim in an IPCC report (citing a WWF report which cited an article in New Scientist), that the Himalayan glaciers would be gone by 2035. The claim originated with Syed Hasnain, who subsequently took a job at The Energy and Resources Institute (TERI), the Delhi-based company of which Dr Pachauri is director-general, and there his glacier claim enabled TERI to win a share of a three-million-euro grant from the European Union. No wonder Dr Pachauri might well not have wanted the 2035 claim challenged.

Yet Raina was right, it proved to be the IPCC’s most high-profile blunder, and Dr Pachauri had to withdraw both it and his “voodoo” remark. The scandal led to a highly critical report into the IPCC by several of the world’s top science academics, which recommended among other things that the IPCC chair stand down after one term. Dr Pachauri ignored this, kept his job, toured the world while urging others not to, and published a novel, with steamy scenes of seduction of an older man by young women. (He resigned this year following criminal allegations of sexual misconduct with a twenty-nine-year-old female employee, which he denies, and which are subject to police investigation.)

Yet the climate bloggers who constantly smear sceptics managed to avoid even reporting most of this. If you want to follow Dr Pachauri’s career you have to rely on a tireless but self-funded investigative journalist: the Canadian Donna Laframboise. In her chapter in The Facts, Laframboise details how Dr Pachauri has managed to get the world to describe him as a Nobel laureate, even though this is simply not true.

Notice, by the way, how many of these fearless free-thinkers prepared to tell emperors they are naked are women. Susan Crockford, a Canadian zoologist, has steadfastly exposed the myth-making that goes into polar bear alarmism, to the obvious discomfort of the doyens of that field. Jennifer Marohasy of Central Queensland University, by persistently asking why cooling trends recorded at Australian weather stations with no recorded moves were being altered to warming trends, has embarrassed the Bureau of Meteorology into a review of their procedures. Her chapter in The Facts underlines the failure of computer models to predict rainfall.

But male sceptics have scored successes too. There was the case of the paper the IPCC relied upon to show that urban heat islands (the fact that cities are generally warmer than the surrounding countryside, so urbanisation causes local, but not global, warming) had not exaggerated recent warming. This paper turned out—as the sceptic Doug Keenan proved—to be based partly on non-existent data on forty-nine weather stations in China. When corrected, it emerged that the urban heat island effect actually accounted for 40 per cent of the warming in China.

There was the Scandinavian lake sediment core that was cited as evidence of sudden recent warming, when it was actually being used “upside down”—the opposite way the authors of the study thought it should be used: so if anything it showed cooling.

There was the graph showing unprecedented recent warming that turned out to depend on just one larch tree in the Yamal Peninsula in Siberia.

There was the southern hemisphere hockey-stick that had been created by the omission of inconvenient data series.

There was the infamous “hide the decline” incident when a tree-ring-derived graph had been truncated to disguise the fact that it seemed to show recent cooling.

And of course there was the mother of all scandals, the “hockey stick” itself: a graph that purported to show the warming of the last three decades of the twentieth century as unprecedented in a millennium, a graph that the IPCC was so thrilled with that it published it six times in its third assessment report and displayed it behind the IPCC chairman at his press conference. It was a graph that persuaded me to abandon my scepticism (until I found out about its flaws), because I thought Nature magazine would never have published it without checking. And it is a graph that was systematically shown by Steven McIntyre and Ross McKitrick to be wholly misleading, as McKitrick recounts in glorious detail in his chapter in The Facts.

Its hockey-stick shape depended heavily on one set of data from bristlecone pine trees in the American south-west, enhanced by a statistical approach to over-emphasise some 200 times any hockey-stick shaped graph. Yet bristlecone tree-rings do not, according to those who collected the data, reflect temperature at all. What is more, the scientist behind the original paper, Michael Mann, had known all along that his data depended heavily on these inappropriate trees and a few other series, because when finally prevailed upon to release his data he accidentally included a file called “censored” that proved as much: he had tested the effect of removing the bristlecone pine series and one other, and found that the hockey-stick shape disappeared.

In March this year Dr Mann published a paper claiming the Gulf Stream was slowing down. This garnered headlines all across the world. Astonishingly, his evidence that the Gulf Stream is slowing down came not from the Gulf Stream, but from “proxies” which included—yes—bristlecone pine trees in Arizona, upside-down lake sediments in Scandinavia and larch trees in Siberia.

The democratisation of science

Any one of these scandals in, say, medicine might result in suspensions, inquiries or retractions. Yet the climate scientific establishment repeatedly reacts as if nothing is wrong. It calls out any errors on the lukewarming end, but ignores those on the exaggeration end. That complacency has shocked me, and done more than anything else to weaken my long-standing support for science as an institution. I repeat that I am not a full sceptic of climate change, let alone a “denier”. I think carbon-dioxide-induced warming during this century is likely, though I think it is unlikely to prove rapid and dangerous. So I don’t agree with those who say the warming is all natural, or all driven by the sun, or only an artefact of bad measurement, but nor do I think anything excuses bad scientific practice in support of the carbon dioxide theory, and every time one of these scandals erupts and the scientific establishment asks us to ignore it, I wonder if the extreme sceptics are not on to something. I feel genuinely betrayed by the profession that I have spent so much of my career championing.

There is, however, one good thing that has happened to science as a result of the climate debate: the democratisation of science by sceptic bloggers. It is no accident that sceptic sites keep winning the “Bloggies” awards. There is nothing quite like them for massive traffic, rich debate and genuinely open peer review. Following Steven McIntyre on tree rings, Anthony Watts or Paul Homewood on temperature records, Judith Curry on uncertainty, Willis Eschenbach on clouds or ice cores, or Andrew Montford on media coverage has been one of the delights of recent years for those interested in science. Papers that had passed formal peer review and been published in journals have nonetheless been torn apart in minutes on the blogs. There was the time Steven McIntyre found that an Antarctic temperature trend arose “entirely from the impact of splicing the two data sets together”. Or when Willis Eschenbach showed a published chart had “cut the modern end of the ice core carbon dioxide record short, right at the time when carbon dioxide started to rise again” about 8000 years ago, thus omitting the startling but inconvenient fact that carbon dioxide levels rose while temperatures fell over the following millennia.

Scientists don’t like this lèse majesté, of course. But it’s the citizen science that the internet has long promised. This is what eavesdropping on science should be like—following the twists and turns of each story, the ripostes and counter-ripostes, making up your own mind based on the evidence. And that is precisely what the non-sceptical side just does not get. Its bloggers are almost universally wearily condescending. They are behaving like sixteenth-century priests who do not think the Bible should be translated into English.

Renegade heretics in science itself are especially targeted. The BBC was subjected to torrents of abuse for even interviewing Bob Carter, a distinguished geologist and climate science expert who does not toe the alarmed line and who is one of the editors of Climate Change Reconsidered, a serious and comprehensive survey of the state of climate science organised by the Non-governmental Panel on Climate Change and ignored by the mainstream media.

Judith Curry of Georgia Tech moved from alarm to mild scepticism and has endured vitriolic criticism for it. She recently wrote:

There is enormous pressure for climate scientists to conform to the so-called consensus. This pressure comes not only from politicians, but from federal funding agencies, universities and professional societies, and scientists themselves who are green activists and advocates. Reinforcing this consensus are strong monetary, reputational, and authority interests. The closing of minds on the climate change issue is a tragedy for both science and society.

The distinguished Swedish meteorologist Lennart Bengtsson was so frightened for his own family and his health after he announced last year that he was joining the advisory board of the Global Warming Policy Foundation that he withdrew, saying, “It is a situation that reminds me about the time of McCarthy.”

The astrophysicist Willie Soon was falsely accused by a Greenpeace activist of failing to disclose conflicts of interest to an academic journal, an accusation widely repeated by mainstream media.

Clearing the middle ground

Much of this climate war parallels what has happened with Islamism, and it is the result of a similar deliberate policy of polarisation and silencing of debate. Labelling opponents “Islamophobes” or “deniers” is in the vast majority of cases equally inaccurate and equally intended to polarise. As Asra Nomani wrote in the Washington Post recently, a community of anti-blasphemy police arose out of a deliberate policy decision by the Organisation of Islamic Cooperation:

and began trying to control the debate on Islam. This wider corps throws the label of “Islamophobe” on pundits, journalists and others who dare to talk about extremist ideology in the religion … The insults may look similar to Internet trolling and vitriolic comments you can find on any blog or news site. But they’re more coordinated, frightening and persistent.

Compare that to what happened to Roger Pielke Jr, as recounted by James Delingpole in The Facts. Pielke is a professor of environmental studies at the University of Colorado and a hugely respected expert on disasters. He is no denier, thinking man-made global warming is real. But in his own area of expertise he is very clear that the rise in insurance losses is because the world is getting wealthier and we have more stuff to lose, not because more storms are happening. This is incontrovertibly true, and the IPCC agrees with him. But when he said this on Nate Silver’s FiveThirtyEight website he and Silver were savaged by commenters, led by one Rob Honeycutt. Crushed by the fury he had unleashed, Silver apologised and dropped Pielke as a contributor.

Rob Honeycutt and his allies knew what they were doing. Delingpole points out that Honeycutt (on a different website) urged people to “send in the troops to hammer down” anything moderate or sceptical, and to “grow the team of crushers”. Those of us who have been on the end of this sort of stuff know it is exactly like what the blasphemy police do with Islamophobia. We get falsely labelled “deniers” and attacked for heresy in often the most ad-hominem way.

Even more shocking has been the bullying lynch mob assembled this year by alarmists to prevent the University of Western Australia, erstwhile employers of the serially debunked conspiracy theorist Stephan Lewandowsky, giving a job to the economist Bjorn Lomborg. The grounds were that Lomborg is a “denier”. But he’s not. He does not challenge the science at all. He challenges on economic grounds some climate change policies, and the skewed priorities that lead to the ineffective spending of money on the wrong environmental solutions. His approach has been repeatedly vindicated over many years in many different topics, by many of the world’s leading economists. 
Yet there was barely a squeak of protest from the academic establishment at the way he was howled down and defamed for having the temerity to try to set up a research group at a university.

Well, internet trolls are roaming the woods in every subject, so what am I complaining about? The difference is that in the climate debate they have the tacit or explicit support of the scientific establishment. Venerable bodies like the Royal Society almost never criticise journalists for being excessively alarmist, only for being too lukewarm, and increasingly behave like pseudoscientists, explaining away inconvenient facts.

Making excuses for failed predictions

For example, scientists predicted a retreat of Antarctic sea ice but it has expanded instead, and nowadays they are claiming, like any astrologer, that this is because of warming after all. “Please,” says Mark Steyn in The Facts:

No tittering, it’s so puerile—every professor of climatology knows that the thickest ice ever is a clear sign of thin ice, because as the oceans warm, glaciers break off the Himalayas and are carried by the El Ninja down the Gore Stream past the Cape of Good Horn where they merge into the melting ice sheet, named after the awareness-raising rapper Ice Sheet …

Or consider this example, from the Royal Society’s recent booklet on climate change:

Does the recent slowdown of warming mean that climate change is no longer happening? No. Since the very warm surface temperatures of 1998 which followed the strong 1997-98 El Niño, the increase in average surface temperature has slowed relative to the previous decade of rapid temperature increases, with more of the excess heat being stored in the oceans.

You would never know from this that the “it’s hiding in the oceans” excuse is just one unproven hypothesis—and one that implies that natural variation exaggerated the warming in the 1990s, so reinforcing the lukewarm argument. Nor would you know (as Andrew Bolt recounts in his chapter in The Facts) that the pause in global warming contradicts specific and explicit predictions such as this, from the UK Met Office: “by 2014 we’re predicting it will be 0.3 degrees warmer than in 2004”. Or that the length of the pause is now past the point where many scientists said it would disprove the hypothesis of rapid man-made warming. Dr Phil Jones, head of the Climatic Research Unit at the University of East Anglia, said in 2009: “Bottom line: the ‘no upward trend’ has to continue for a total of 15 years before we get worried.” It now has.

Excusing failed predictions is a staple of astrology; it’s the way pseudoscientists argue. In science, as Karl Popper long ago insisted, if you make predictions and they fail, you don’t just make excuses and insist you’re even more right than before. The Royal Society once used to promise “never to give their opinion, as a body, upon any subject”. Its very motto is “nullius in verba”: take nobody’s word for it. Now it puts out catechisms of what you must believe in. Surely, the handing down of dogmas is for churches, not science academies. Expertise, authority and leadership should count for nothing in science. The great Thomas Henry Huxley put it this way: “The improver of natural knowledge absolutely refuses to acknowledge authority, as such. For him, scepticism is the highest of duties; blind faith the one unpardonable sin.” Richard Feynman was even pithier: “Science is the belief in the ignorance of experts.”

The harm to science

I dread to think what harm this episode will have done to the reputation of science in general when the dust has settled. Science will need a reformation. Garth Paltridge is a distinguished Australian climate scientist, who, in The Facts, pens a wise paragraph that I fear will be the epitaph of climate science:

We have at least to consider the possibility that the scientific establishment behind the global warming issue has been drawn into the trap of seriously overstating the climate problem—or, what is much the same thing, of seriously understating the uncertainties associated with the climate problem—in its effort to promote the cause. It is a particularly nasty trap in the context of science, because it risks destroying, perhaps for centuries to come, the unique and hard-won reputation for honesty which is the basis for society’s respect for scientific endeavour.

And it’s not working anyway. Despite avalanches of money being spent on research to find evidence of rapid man-made warming, despite even more spent on propaganda and marketing and subsidising renewable energy, the public remains unconvinced. The most recent polling data from Gallup shows the number of Americans who worry “a great deal” about climate change is down slightly on thirty years ago, while the number who worry “not at all” has doubled from 12 per cent to 24 per cent—and now exceeds the number who worry “only a little” or “a fair amount”. All that fear-mongering has achieved less than nothing: if anything it has hardened scepticism.

None of this would matter if it was just scientific inquiry, though that rarely comes cheap in itself. The big difference is that these scientists who insist that we take their word for it, and who get cross if we don’t, are also asking us to make huge, expensive and risky changes to the world economy and to people’s livelihoods. They want us to spend a fortune getting emissions down as soon as possible. And they want us to do that even if it hurts poor people today, because, they say, their grandchildren (who, as Nigel Lawson points out, in The Facts, and their models assume, are going to be very wealthy) matter more.

Yet they are not prepared to debate the science behind their concern. That seems wrong to me.

Matt Ridley is an English science journalist whose books include The Rational Optimist: How Prosperity Evolves. A member of the House of Lords, he has a website at www.mattridley.co.uk. He declares an interest in coal through the leasing of land for mining.

Thursday, June 18, 2015

Stem cell


From Wikipedia, the free encyclopedia

Stem cell
MSC high magnification.jpg
Transmission electron micrograph of an adult stem cell displaying typical ultrastructural characteristics.
Details
Latin Cellula praecursoria
Identifiers
Code TH H2.00.01.0.00001
TH H1.00.01.0.00028, H2.00.01.0.00001
FMA 63368
Anatomical terminology

Stem cells are undifferentiated biological cells that can differentiate into specialized cells and can divide (through mitosis) to produce more stem cells. They are found in multicellular organisms. In mammals, there are two broad types of stem cells: embryonic stem cells, which are isolated from the inner cell mass of blastocysts, and adult stem cells, which are found in various tissues. In adult organisms, stem cells and progenitor cells act as a repair system for the body, replenishing adult tissues. In a developing embryo, stem cells can differentiate into all the specialized cells—ectoderm, endoderm and mesoderm (see induced pluripotent stem cells)—but also maintain the normal turnover of regenerative organs, such as blood, skin, or intestinal tissues.

There are three known accessible sources of autologous adult stem cells in humans:
  1. Bone marrow, which requires extraction by harvesting, that is, drilling into bone (typically the femur or iliac crest).
  2. Adipose tissue (lipid cells), which requires extraction by liposuction.
  3. Blood, which requires extraction through apheresis, wherein blood is drawn from the donor (similar to a blood donation), and passed through a machine that extracts the stem cells and returns other portions of the blood to the donor.
Stem cells can also be taken from umbilical cord blood just after birth. Of all stem cell types, autologous harvesting involves the least risk. By definition, autologous cells are obtained from one's own body, just as one may bank his or her own blood for elective surgical procedures.

Adult stem cells are frequently used in medical therapies, for example in bone marrow transplantation. Stem cells can now be artificially grown and transformed (differentiated) into specialized cell types with characteristics consistent with cells of various tissues such as muscles or nerves. Embryonic cell lines and autologous embryonic stem cells generated through Somatic-cell nuclear transfer or dedifferentiation have also been proposed as promising candidates for future therapies.[1] Research into stem cells grew out of findings by Ernest A. McCulloch and James E. Till at the University of Toronto in the 1960s.[2][3]

Properties

The classical definition of a stem cell requires that it possess two properties:
  • Self-renewal: the ability to go through numerous cycles of cell division while maintaining the undifferentiated state.
  • Potency: the capacity to differentiate into specialized cell types. In the strictest sense, this requires stem cells to be either totipotent or pluripotent—to be able to give rise to any mature cell type, although multipotent or unipotent progenitor cells are sometimes referred to as stem cells. Apart from this it is said that stem cell function is regulated in a feed back mechanism.

Self-renewal

Two mechanisms exist to ensure that a stem cell population is maintained:
  1. Obligatory asymmetric replication: a stem cell divides into one mother cell that is identical to the original stem cell, and another daughter cell that is differentiated.
  2. Stochastic differentiation: when one stem cell develops into two differentiated daughter cells, another stem cell undergoes mitosis and produces two stem cells identical to the original.

Potency definition

Pluripotent, embryonic stem cells originate as inner cell mass (ICM) cells within a blastocyst. These stem cells can become any tissue in the body, excluding a placenta. Only cells from an earlier stage of the embryo, known as the morula, are totipotent, able to become all tissues in the body and the extraembryonic placenta.

Human embryonic stem cells

A: Stem cell colonies that are not yet differentiated.

B: Nerve cells, an example of a cell type after differentiation.

Potency specifies the differentiation potential (the potential to differentiate into different cell types) of the stem cell.[4]
  • Totipotent (a.k.a. omnipotent) stem cells can differentiate into embryonic and extraembryonic cell types. Such cells can construct a complete, viable organism.[4] These cells are produced from the fusion of an egg and sperm cell. Cells produced by the first few divisions of the fertilized egg are also totipotent.[5]
  • Pluripotent stem cells are the descendants of totipotent cells and can differentiate into nearly all cells,[4] i.e. cells derived from any of the three germ layers.[6]
  • Multipotent stem cells can differentiate into a number of cell types, but only those of a closely related family of cells.[4]
  • Oligopotent stem cells can differentiate into only a few cell types, such as lymphoid or myeloid stem cells.[4]
  • Unipotent cells can produce only one cell type, their own,[4] but have the property of self-renewal, which distinguishes them from non-stem cells (e.g. progenitor cells, muscle stem cells).

Identification

In practice, stem cells are identified by whether they can regenerate tissue. For example, the defining test for bone marrow or hematopoietic stem cells (HSCs) is the ability to transplant the cells and save an individual without HSCs. This demonstrates that the cells can produce new blood cells over a long term. It should also be possible to isolate stem cells from the transplanted individual, which can themselves be transplanted into another individual without HSCs, demonstrating that the stem cell was able to self-renew.

Properties of stem cells can be illustrated in vitro, using methods such as clonogenic assays, in which single cells are assessed for their ability to differentiate and self-renew.[7][8] Stem cells can also be isolated by their possession of a distinctive set of cell surface markers. However, in vitro culture conditions can alter the behavior of cells, making it unclear whether the cells will behave in a similar manner in vivo. There is considerable debate as to whether some proposed adult cell populations are truly stem cells.

Embryonic

Embryonic stem (ES) cells are stem cells derived from the inner cell mass of a blastocyst, an early-stage embryo.[9] Human embryos reach the blastocyst stage 4–5 days post fertilization, at which time they consist of 50–150 cells. ES cells are pluripotent and give rise during development to all derivatives of the three primary germ layers: ectoderm, endoderm and mesoderm. In other words, they can develop into each of the more than 200 cell types of the adult body when given sufficient and necessary stimulation for a specific cell type. They do not contribute to the extra-embryonic membranes or the placenta.
Nearly all research to date has made use of mouse embryonic stem cells (mES) or human embryonic stem cells (hES). Both have the essential stem cell characteristics, yet they require very different environments in order to maintain an undifferentiated state. Mouse ES cells are grown on a layer of gelatin as an extracellular matrix (for support) and require the presence of leukemia inhibitory factor (LIF). Human ES cells are grown on a feeder layer of mouse embryonic fibroblasts (MEFs) and require the presence of basic fibroblast growth factor (bFGF or FGF-2).[10] Without optimal culture conditions or genetic manipulation,[11] embryonic stem cells will rapidly differentiate.

A human embryonic stem cell is also defined by the expression of several transcription factors and cell surface proteins. The transcription factors Oct-4, Nanog, and Sox2 form the core regulatory network that ensures the suppression of genes that lead to differentiation and the maintenance of pluripotency.[12] The cell surface antigens most commonly used to identify hES cells are the glycolipids stage specific embryonic antigen 3 and 4 and the keratan sulfate antigens Tra-1-60 and Tra-1-81. The molecular definition of a stem cell includes many more proteins and continues to be a topic of research.[13]

There are currently no approved treatments using embryonic stem cells. The first human trial was approved by the US Food and Drug Administration in January 2009.[14] However, the human trial was not initiated until October 13, 2010 in Atlanta for spinal injury victims. On November 14, 2011 the company conducting the trial announced that it will discontinue further development of its stem cell programs.[15] ES cells, being pluripotent cells, require specific signals for correct differentiation—if injected directly into another body, ES cells will differentiate into many different types of cells, causing a teratoma. Differentiating ES cells into usable cells while avoiding transplant rejection are just a few of the hurdles that embryonic stem cell researchers still face.[16] Many nations currently have moratoria on either ES cell research or the production of new ES cell lines. Because of their combined abilities of unlimited expansion and pluripotency, embryonic stem cells remain a theoretically potential source for regenerative medicine and tissue replacement after injury or disease.

Fetal

The primitive stem cells located in the organs of fetuses are referred to as fetal stem cells.[17] There are two types of fetal stem cells:
  1. Fetal proper stem cells come from the tissue of the fetus proper, and are generally obtained after an abortion. These stem cells are not immortal but have a high level of division and are multipotent.
  2. Extraembryonic fetal stem cells come from extraembryonic membranes, and are generally not distinguished from adult stem cells. These stem cells are acquired after birth, they are not immortal but have a high level of cell division, and are pluripotent.[18]

Adult

Stem cell division and differentiation. A: stem cell; B: progenitor cell; C: differentiated cell; 1: symmetric stem cell division; 2: asymmetric stem cell division; 3: progenitor division; 4: terminal differentiation

Adult stem cells, also called somatic (from Greek Σωματικóς, "of the body") stem cells, are stem cells which maintain and repair the tissue in which they are found.[19] They can be found in children, as well as adults.[20]
Pluripotent adult stem cells are rare and generally small in number, but they can be found in umbilical cord blood and other tissues.[21] Bone marrow is a rich source of adult stem cells,[22] which have been used in treating several conditions including spinal cord injury,[23] liver cirrhosis,[24] chronic limb ischemia [25] and end stage heart failure.[26] The quantity of bone marrow stem cells declines with age and is greater in males than females during reproductive years.[27] Much adult stem cell research to date has aimed to characterize their potency and self-renewal capabilities.[28] DNA damage accumulates with age in both stem cells and the cells that comprise the stem cell environment. This accumulation is considered to be responsible, at least in part, for increasing stem cell dysfunction with aging (see DNA damage theory of aging).[29]

Most adult stem cells are lineage-restricted (multipotent) and are generally referred to by their tissue origin (mesenchymal stem cell, adipose-derived stem cell, endothelial stem cell, dental pulp stem cell, etc.).[30][31]

Adult stem cell treatments have been successfully used for many years to treat leukemia and related bone/blood cancers through bone marrow transplants.[32] Adult stem cells are also used in veterinary medicine to treat tendon and ligament injuries in horses.[33]

The use of adult stem cells in research and therapy is not as controversial as the use of embryonic stem cells, because the production of adult stem cells does not require the destruction of an embryo. Additionally, in instances where adult stem cells are obtained from the intended recipient (an autograft), the risk of rejection is essentially non-existent. Consequently, more US government funding is being provided for adult stem cell research.[34]

Amniotic

Multipotent stem cells are also found in amniotic fluid. These stem cells are very active, expand extensively without feeders and are not tumorigenic. Amniotic stem cells are multipotent and can differentiate in cells of adipogenic, osteogenic, myogenic, endothelial, hepatic and also neuronal lines.[35] Amniotic stem cells are a topic of active research.

Use of stem cells from amniotic fluid overcomes the ethical objections to using human embryos as a source of cells. Roman Catholic teaching forbids the use of embryonic stem cells in experimentation; accordingly, the Vatican newspaper "Osservatore Romano" called amniotic stem cells "the future of medicine".[36]

It is possible to collect amniotic stem cells for donors or for autologuous use: the first US amniotic stem cells bank [37][38] was opened in 2009 in Medford, MA, by Biocell Center Corporation[39][40][41] and collaborates with various hospitals and universities all over the world.[42]

Cord blood

A certain kind of cord blood stem cell (CB-SC) is multipotent and displays embryonic and hematopoietic characteristics. Phenotypic characterization demonstrates that (CB-SCs) display embryonic cell markers (e.g., transcription factors OCT-4 and Nanog, stage-specific embryonic antigen (SSEA)-3, and SSEA-4) and leukocyte common antigen CD45, but that they are negative for blood cell lineage markers (e.g., CD1a, CD3, CD4, CD8, CD11b, CD11c, CD13, CD14, CD19, CD20, CD34, CD41a, CD41b, CD83, CD90, CD105, and CD133).[43][44]
Additionally, CB-SCs display very low immunogenicity as indicated by expression of a very low level of major histocompatibility complex (MHC) antigens and failure to stimulate the proliferation of allogeneic lymphocytes.[43][45] They can give rise to three embryonic layer-derived cells in the presence of different inducers.[43][46]

More specifically, CB-SCs tightly adhere to culture dishes with a large rounded morphology and are resistant to common detaching methods (trypsin/EDTA).[43][45][46] CB-SCs are the active agent in stem cell educator therapy, which has therapeutic potential against autoimmune diseases like type 1 diabetes according to studies by Yong Zhao et al.[44][47][48][49][unreliable medical source?]

Induced pluripotent

These are not adult stem cells, but rather adult cells (e.g. epithelial cells) reprogrammed to give rise to pluripotent capabilities. Using genetic reprogramming with protein transcription factors, pluripotent stem cells equivalent to embryonic stem cells have been derived from human adult skin tissue.[50][51][52] Shinya Yamanaka and his colleagues at Kyoto University used the transcription factors Oct3/4, Sox2, c-Myc, and Klf4[50] in their experiments on cells from human faces. Junying Yu, James Thomson, and their colleagues at the University of Wisconsin–Madison used a different set of factors, Oct4, Sox2, Nanog and Lin28,[50] and carried out their experiments using cells from human foreskin.
As a result of the success of these experiments, Ian Wilmut, who helped create the first cloned animal Dolly the Sheep, has announced that he will abandon somatic cell nuclear transfer as an avenue of research.[53]

Frozen blood samples can be used as a source of induced pluripotent stem cells, opening a new avenue for obtaining the valued cells.[54]

Lineage

To ensure self-renewal, stem cells undergo two types of cell division (see Stem cell division and differentiation diagram). Symmetric division gives rise to two identical daughter cells both endowed with stem cell properties. Asymmetric division, on the other hand, produces only one stem cell and a progenitor cell with limited self-renewal potential. Progenitors can go through several rounds of cell division before terminally differentiating into a mature cell. It is possible that the molecular distinction between symmetric and asymmetric divisions lies in differential segregation of cell membrane proteins (such as receptors) between the daughter cells.[55]
An alternative theory is that stem cells remain undifferentiated due to environmental cues in their particular niche. Stem cells differentiate when they leave that niche or no longer receive those signals. Studies in Drosophila germarium have identified the signals decapentaplegic and adherens junctions that prevent germarium stem cells from differentiating.[56][57]

Treatments

Diseases and conditions where stem cell treatment is being investigated.

Diseases and conditions where stem cell treatment is being investigated include:
Stem cell therapy is the use of stem cells to treat or prevent a disease or condition. Bone marrow transplant is a crude form of stem cell therapy that has been used clinically for many years without controversy. No stem cell therapies other than bone marrow transplant are widely used.[71][72]

Research is underway to develop various sources for stem cells, and to apply stem cell treatments for neurodegenerative diseases and conditions, diabetes, heart disease, and other conditions.[73]

In more recent years, with the ability of scientists to isolate and culture embryonic stem cells, and with scientists' growing ability to create stem cells using somatic cell nuclear transfer and techniques to created induced pluripotent stem cells, controversy has crept in, both related to abortion politics and to human cloning.

Disadvantages

Stem cell treatments may require immunosuppression because of a requirement for radiation before the transplant to remove the patient's previous cells, or because the patient's immune system may target the stem cells. One approach to avoid the second possibility is to use stem cells from the same patient who is being treated.

Pluripotency in certain stem cells could also make it difficult to obtain a specific cell type. It is also difficult to obtain the exact cell type needed, because not all cells in a population differentiate uniformly. Undifferentiated cells can create tissues other than desired types.[74]

Some stem cells form tumors after transplantation; pluripotency is linked to tumor formation especially in embryonic stem cells, fetal proper stem cells, induced pluripotent stem cells. Fetal proper stem cells form tumors despite multipotency.[citation needed]

Hepatotoxicity and drug-induced liver injury account for a substantial number of failures of new drugs in development and market withdrawal, highlighting the need for screening assays such as stem cell-derived hepatocyte-like cells, that are capable of detecting toxicity early in the drug development process.[75]

Research patents


Some of the fundamental patents covering human embryonic stem cells are owned by the Wisconsin Alumni Research Foundation (WARF) - they are patents 5,843,780, 6,200,806, and 7,029,913 invented by James A. Thomson. WARF does not enforce these patents against academic scientists, but does enforce them against companies.[76]

In 2006, a request for the US Patent and Trademark Office (USPTO) to re-examine the three patents was filed by the Public Patent Foundation on behalf of its client, the non-profit patent-watchdog group Consumer Watchdog (formerly the Foundation for Taxpayer and Consumer Rights).[76] In the re-examination process, which involves several rounds of discussion between the USTPO and the parties, the USPTO initially agreed with Consumer Watchdog and rejected all the claims in all three patents,[77] however in response, WARF amended the claims of all three patents to make them more narrow, and in 2008 the USPTO found the amended claims in all three patents to be patentable. The decision on one of the patents (7,029,913) was appealable, while the decisions on the other two were not.[78][79] Consumer Watchdog appealed the granting of the '913 patent to the USTPO's Board of Patent Appeals and Interferences (BPAI) which granted the appeal, and in 2010 the BPAI decided that the amended claims of the '913 patent were not patentable.[80] However, WARF was able to re-open prosecution of the case and did so, amending the claims of the '913 patent again to make them more narrow, and in January 2013 the amended claims were allowed.[81]

In July 2013, Consumer Watchdog announced that it would appeal the decision to allow the claims of the '913 patent to the US Court of Appeals for the Federal Circuit (CAFC), the federal appeals court that hears patent cases.[82] At a hearing in December 2013, the CAFC raised the question of whether Consumer Watchdog had legal standing to appeal; the case could not proceed until that issue was resolved.[83]

Key research events

  • 1908: The term "stem cell" was proposed for scientific use by the Russian histologist Alexander Maksimov (1874–1928) at congress of hematologic society in Berlin. It postulated existence of haematopoietic stem cells.
  • 1960s: Joseph Altman and Gopal Das present scientific evidence of adult neurogenesis, ongoing stem cell activity in the brain; their reports contradict Cajal's "no new neurons" dogma and are largely ignored.
  • 1963: Becker, McCulloch and Till illustrate the presence of self-renewing cells in mouse bone marrow.
  • 1968: Bone marrow transplant between two siblings successfully treats SCID.
  • 1978: Haematopoietic stem cells are discovered in human cord blood.
  • 1981: Mouse embryonic stem cells are derived from the inner cell mass by scientists Martin Evans, Matthew Kaufman, and Gail R. Martin. Gail Martin is attributed for coining the term "Embryonic Stem Cell".[84]
  • 1992: Neural stem cells are cultured in vitro as neurospheres.
  • 1995: Indian scientist Dr. B.G. Matapurkar pioneers in adult stem-cell research with clinical utilization of research in the body and neo-regeneration of tissues and organs in the body. Received International Patent from US Patent Office (USA) in 2001 (effective from 1995). Clinical utilization in human body also demonstrated and patented in 60 patients (World Journal of Surgery-1999[85] and 1991[86]).
  • 1997: Dr. B.G. Matapurkar's surgical technique on regeneration of tissues and organs is published.[87] Regeneration of fallopian tube and uterus is published.[88]
  • 1997: Leukemia is shown to originate from a haematopoietic stem cell, the first direct evidence for cancer stem cells.
  • 1998: James Thomson and coworkers derive the first human embryonic stem cell line at the University of Wisconsin–Madison.[89]
  • 1998: John Gearhart (Johns Hopkins University) extracted germ cells from fetal gonadal tissue (primordial germ cells) before developing pluripotent stem cell lines from the original extract.
  • 2000s: Several reports of adult stem cell plasticity are published.
  • 2001: Scientists at Advanced Cell Technology clone first early (four- to six-cell stage) human embryos for the purpose of generating embryonic stem cells.[90]
  • 2003: Dr. Songtao Shi of NIH discovers new source of adult stem cells in children's primary teeth.[91]
  • 2004–2005: Korean researcher Hwang Woo-Suk claims to have created several human embryonic stem cell lines from unfertilised human oocytes. The lines were later shown to be fabricated.
  • 2005: Researchers at Kingston University in England claim to have discovered a third category of stem cell, dubbed cord-blood-derived embryonic-like stem cells (CBEs), derived from umbilical cord blood. The group claims these cells are able to differentiate into more types of tissue than adult stem cells.
  • 2005: Researchers at UC Irvine's Reeve-Irvine Research Center are able to partially restore the ability of rats with paralyzed spines to walk through the injection of human neural stem cells.[92]

Yong Zhao, University of Illinois at Chicago
  • April 2006 Scientists at the University of Illinois at Chicago identified novel stem cells from the umbilical cord blood with embryonic and hematopoietic characteristics.[43]
  • August 2006: Kazutoshi Takahashi and Shinya Yamanaka publish evidence of Induced pluripotent stem cells in mice in the journal Cell.[93]
  • November 2006: Yong Zhao et al. revealed the immune regulation of T lymphocytes by Cord Blood-Derived Multipotent Stem Cells (CB-SCs).[45]
  • October 2006: Scientists at Newcastle University in England create the first ever artificial liver cells using umbilical cord blood stem cells.[94][95]
  • January 2007: Scientists at Wake Forest University led by Dr. Anthony Atala and Harvard University report discovery of a new type of stem cell in amniotic fluid.[96] This may potentially provide an alternative to embryonic stem cells for use in research and therapy.[97]
  • June 2007: Research reported by three different groups shows that normal skin cells can be reprogrammed to an embryonic state in mice.[98] In the same month, scientist Shoukhrat Mitalipov reports the first successful creation of a primate stem cell line through somatic cell nuclear transfer[99]

    Martin Evans, a co-winner of the Nobel Prize in recognition of his gene targeting work.
  • October 2007: Mario Capecchi, Martin Evans, and Oliver Smithies win the 2007 Nobel Prize for Physiology or Medicine for their work on embryonic stem cells from mice using gene targeting strategies producing genetically engineered mice (known as knockout mice) for gene research.[100]
  • November 2007: Human induced pluripotent stem cells: Two similar papers released by their respective journals prior to formal publication: in Cell by Kazutoshi Takahashi and Shinya Yamanaka, "Induction of pluripotent stem cells from adult human fibroblasts by defined factors",[101] and in Science by Junying Yu, et al., from the research group of James Thomson, "Induced pluripotent stem cell lines derived from human somatic cells":[102] pluripotent stem cells generated from mature human fibroblasts. It is possible now to produce a stem cell from almost any other human cell instead of using embryos as needed previously, albeit the risk of tumorigenesis due to c-myc and retroviral gene transfer remains to be determined.
  • January 2008: Robert Lanza and colleagues at Advanced Cell Technology and UCSF create the first human embryonic stem cells without destruction of the embryo.[103]
  • January 2008: Development of human cloned blastocysts following somatic cell nuclear transfer with adult fibroblasts[104]
  • February 2008: Generation of pluripotent stem cells from adult mouse liver and stomach: these iPS cells seem to be more similar to embryonic stem cells than the previously developed iPS cells and not tumorigenic, moreover genes that are required for iPS cells do not need to be inserted into specific sites, which encourages the development of non-viral reprogramming techniques.[105]
  • March 2008-The first published study of successful cartilage regeneration in the human knee using autologous adult mesenchymal stem cells is published by clinicians from Regenerative Sciences[106]
  • October 2008: Sabine Conrad and colleagues at Tübingen, Germany generate pluripotent stem cells from spermatogonial cells of adult human testis by culturing the cells in vitro under leukemia inhibitory factor (LIF) supplementation.[107]
  • 30 October 2008: Embryonic-like stem cells from a single human hair.[108]
  • January 2009: Yong Zhao and colleagues confirmed the reversal of autoimmune-caused type 1 diabetes by Cord Blood-Derived Multipotent Stem Cells (CB-SCs) in an animal experiment.[44][47]
  • 1 March 2009: Andras Nagy, Keisuke Kaji, et al. discover a way to produce embryonic-like stem cells from normal adult cells by using a novel "wrapping" procedure to deliver specific genes to adult cells to reprogram them into stem cells without the risks of using a virus to make the change.[109][110][111] The use of electroporation is said to allow for the temporary insertion of genes into the cell.[112][112][113][114]
  • 28 May 2009 Kim et al. announced that they had devised a way to manipulate skin cells to create patient specific "induced pluripotent stem cells" (iPS), claiming it to be the 'ultimate stem cell solution'.[115]
  • 11 October 2010 First trial of embryonic stem cells in humans.[116]
  • 25 October 2010: Ishikawa et al. write in the Journal of Experimental Medicine that research shows that transplanted cells that contain their new host's nuclear DNA could still be rejected by the individual's immune system due to foreign mitochondrial DNA. Tissues made from a person's stem cells could therefore be rejected, because mitochondrial genomes tend to accumulate mutations.[117]
  • 2011: Israeli scientist Inbar Friedrich Ben-Nun led a team which produced the first stem cells from endangered species, a breakthrough that could save animals in danger of extinction.[118]
  • January 2012: The human clinical trial of treating type 1 diabetes with lymphocyte modification using Cord Blood-Derived Multipotent Stem Cells (CB-SCs) achieved an improvement of C-peptide levels, reduced the median glycated hemoglobin A1C (HbA1c) values, and decreased the median daily dose of insulin in both human patient groups with and without residual beta cell function.[48][49] Yong Zhao's Stem Cell Educator Therapy appears "so simple and so safe"[119]
  • October 2012: Positions of nucleosomes in mouse embryonic stem cells and the changes in their positions during differentiation to neural progenitor cells and embryonic fibroblasts are determined with single-nucleotide resolution.[120]
  • 2012: Katsuhiko Hayashi used mouse skin cells to create stem cells and then used these stem cells to create mouse eggs. These eggs were then fertilized and produced healthy baby offspring. These latter mice were able to have their own babies.[121]
  • 2013: First time lab grown meat made from muscle stem-cells has been cooked and tasted.[122]
  • 2013: First time mice adult cells were reprogrammed into stem cells in vivo.[123]
  • 2013: Scientists at Scotland's Heriot-Watt University developed a 3D printer that can produce clusters of living human embryonic stem cells, potentially allowing complete organs to be printed on demand in the future.[124]
  • 2014: Adult mouse cells reprogrammed to pluripotent stem cells using stimulus-triggered acquisition of pluripotency (STAP);[125] a process which involved bathing blood cells in an acid bath (pH 5.7) for 30minutes at 37 °C.[126] A little over a month after the publication of these findings, errors were discovered and the quality of the research has been widely questioned.[127] Further irregularities regarding the mice used have emerged as recently as June 2014.[128]

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