It's design all the way down

Protein Quality Control Surprise: An Enzyme Can Operate a Stalled Ribosome

Evolution News & Views January 9, 2015 5:17 AM | 

 

A cell is "a well-run factory," according to scientists at the University of Utah. Its protein assembly machines -- ribosomes -- do their work reliably and efficiently most of the time. On rare occasions, though, a nascent protein stalls inside the machine. When that happens, it's a crisis that can kill the cell or lead to serious diseases.

Fortunately, the cell has a plan to rescue itself:

Ribosomes are machines on a protein assembly line, linking together amino acids in an order specified by the genetic code. When something goes wrong, the ribosome can stall, and a quality control crew is summoned to the site. To clean up the mess, the ribosome is disassembled, the blueprint is discarded, and the partly made protein is recycled. (Emphasis added.)

A surprise surfaced when the Utah researchers, in an "extensive biochemical analysis," sought to understand the steps involved in tagging the stalled protein for destruction. Stalling causes the two parts of the ribosome, 40S and 60S, to separate. Immediately afterward, two "rare" quality-control proteins, Ltn1p and Rqc2p, bind to the stalled protein in the 60S part. Ltn1p binds near the exit tunnel and attaches the usual tag for destruction, ubiquitin. (Biochemists have a sense of humor sometimes; the "RING" domain of Ltn1p stands for "Really Interesting New Gene.")

It's the other participant, Rqc2p, that plays an unexpected role: it continues assembling the stalled protein without the benefit of a template or transfer RNA! "In this case, we have a protein, Rqc2, playing a role similar to that of mRNA" (messenger RNA), researcher Adam Frost says. "I love this story because it blurs the lines of what we thought proteins could do." But what kind of information can a template-free protein add to a stalled protein? The story gets even more bizarre:

Yet this study reveals a surprising role for one member of the quality control team, a protein conserved from yeast to man named Rqc2. Before the incomplete protein is recycled, Rqc2 prompts the ribosomes to add just two amino acids (of 20 total) -- alanine and threonine -- over and over, and in any order. Think of an auto assembly line that keeps going despite having lost its instructions. It picks up what it can and slaps it on: horn-wheel-wheel-horn-wheel-wheel-wheel-wheel-horn.

Is this a factory gone berserk? No. Using design thinking, the researchers figured there must be a purpose behind the seemingly wacky process:

Like a half-made car with extra horns and wheels tacked to one end, a truncated protein with an apparently random sequence of alanines and threonines looks strange, and probably doesn't work normally. But the nonsensical sequence likely serves specific purposes. The code could signal that the partial protein must be destroyed, or it could be part of a test to see whether the ribosome is working properly. Evidence suggests that either or both of these processes could be faulty in neurodegenerative diseases such as Alzheimer's, Amyotrophic lateral sclerosis (ALS), or Huntington's.

In fact, earlier experiments have shown a link between Rqc2p and the "heat shock" response of a cell under stress. This response up-regulates the manufacture of heat shock proteins. These proteins come to the aid of a cell that gets too hot, too cold, or oxygen deprived. The heat shock proteins act as chaperones and damage-control agents. They can re-fold partially folded proteins, tag misfolded proteins, or move proteins to safe-houses in the cell. In multicellular eukaryotes, they can even target proteins for the cell surface to be recognized by the immune system.

The linkage between Rqc2p and heat shock gave the researchers a clue. The alanine-threonine tags on the stalled protein (named, whimsically, "CAT tails" for "carboxy-terminal Ala and Thr extensions") might turn on the heat shock response. In their paper in Science, they put the story together:

Integrating our observations, we propose the model schematized in fig. S13. Ribosome stalling leads to dissociation of the 60S and 40S subunits, followed by recognition of the peptidyl-tRNA-60S species by Rqc2p and Ltn1p. Ltn1p ubiquitylates the stalled nascent chain, and this leads to Cdc48 recruitment for extraction and degradation of the incomplete translation product. Rqc2p, through specific binding to Ala(IGC) and Thr(IGU) tRNAs, directs the template-free and 40S-free elongation of the incomplete translation product with CAT tails. CAT tails induce a heat shock response through a mechanism that is yet to be determined.

It wouldn't be enough, in other words, for Ltn1p to tag the bad protein with ubiquitin. All that would do is silently send the protein to the trashcan (the proteasome). No, the cell needs an alarm signal that a ribosome might have gone haywire. The CAT tails added by Rqc2p somehow inform the cell that a heat shock response team is needed to investigate.

To add the CAT tails, Rqc2p cannot rely on the failed ribosome. It also cannot rely on the messenger-RNA and transfer-RNA pathways from the genetic code in the nucleus. Without a template, it has to work autonomously, using its own active sites for alanine and threonine, and the ability to fasten them to the incomplete protein. By stitching on these extra amino acids to the stalled protein, Rqc2p sends something like an SOS message to the cell, using the actual defective protein as evidence. It's all quite elegant and unexpected.

"There are many interesting implications of this work and none of them would have been possible if we didn't follow our curiosity," says Brandman. "The primary driver of discovery has been exploring what you see, and that's what we did. There will never be a substitute for that."

That statement is pregnant with design implications, however unintended. If the researchers stopped at Darwinian ideas of random, purposeless matter in motion, would they have found this new process? It was their curiosity about "what we thought proteins could do" -- what purposeful roles they could play -- that led them to expand our knowledge of cell quality control.

So whether or not these biochemists "believe in" intelligent design -- we assume they don't -- their actions speak louder than words. By viewing the cell as "a well-run factory" with "machines on a protein assembly line," they added to a growing view that "Nature is capable of more than we realize."

Lastly, don't miss that incidental statement about the "member of the quality control team" Rqc2p being "a protein conserved from yeast to man," implying that for hundreds of millions of years, evolution had nothing to do with it.

 

Survival of the kindest?

An Evolutionary Challenge: Explaining Away Compassion, Philanthropy, and Self-Sacrifice

Denyse O'Leary January 9, 2015 11:23 AM | 

 

 

Apart from religion, no subject has vexed naturalists more than why people sacrifice themselves and their wishes, hopes, dreams, and pleasures for others. Branding both philosophy and religion and popular arts and culture for naturalism includes explaining away compassion, philanthropy, and self-sacrifice.

Redefinition is a first step. This entire group of qualities is now loosely called "altruism," a trans-species concept by which, for example, worker ants pass on their genes by serving their queen, who lays lots of eggs, instead of reproducing individually (kin selection).

Kin selection grew legs in 1955 when British geneticist J. B. S. Haldane said, we are told, that he would risk his life for two brothers or eight cousins, to preserve enough of his own genes to justify his death. Evolutionist William Hamilton described the idea mathematically, calling it inclusive fitness. His calculations have been used ever since, and were a key inspiration for Richard Dawkins's The Selfish Gene.

Altruism has been described as "an anomalous thorn in Darwin's side" and a "conundrum that Darwinians would need to solve, given their view of the ruthless struggle among living beings for survival." So, if Darwinizing the mind through altruism and kin selection succeeds, we can account for such human behavior as if we were bees or beavers, which greatly simplifies matters.

E. O. Wilson is widely hailed as the founder of sociobiology (circa 1975), which expounded these theories. Sociobiology later morphed into evolutionary psychology. But then Wilson dramatically abandoned kin selection in 2010 in a Nature paper, "The evolution of eusociality," co-authored with mathematicians. He argued that strict Darwinism (natural selection acting on random mutation) "provides an exact framework for interpreting empirical observations," dispensing with the other theories he had promoted for decades. Over 140 leading biologists signed a letter to Nature, attacking the 2010 paper. Some called his new, strictly Darwin model "unscholarly," "transparently wrong," and "misguided."

What? All this is said of a Darwin-only model, the gold standard of naturalism?

New Atheist evolutionary biologist Jerry Coyne has weighed in, saying that Wilson et al. are "wrong -- dead wrong." Curiously, he admitted, "The 'textbook' explanation, based on a higher relatedness of workers to their sisters than to their own potential offspring, no longer seems feasible. ... But we've known all this for years!" If so, he and fellow evolutionary biologists have been very economical with their accounts of the failures. How else to account for the -- to many people, incomprehensible -- uproar at the time?

Evolutionary psychologist David Sloan Wilson, defending E. O. Wilson, scolded, "This degree of illiteracy about foundational issues is an embarrassment for the field of evolutionary biology." He is perhaps telling us more than he realizes. Neuroscientist Michael Gazzaniga, attempting to defend Wilson, offered:

In the end, Mr. Wilson comes down on the side of what is called multi-level selection -- the view that evolution involves a combination of gene selection, individual selection, kin selection, and group selection. Although he says his new theory opposes the idea of kin selection, in another sense he is simply maintaining that everybody is right. Genes are being selected to benefit the individual and their kin. Genes are also being selected that encourage the individual to participate in a group.

So if Wilson thinks everybody is right, why is Wilson so wrong? As John Gray put the matter in The New Republic, the debate is "an exercise in sectarian intellectual warfare of the kind that is so often fought in and around Darwinism." The uproar shows as well how flimsy the foundations of the Darwinian naturalist account of compassion, empathy, and self-sacrifice in humans have always been.

But that account meets a deeply felt need among naturalists. Generosity, we are told by one research group, leads to evolutionary success:

"When people act generously they feel it is almost instinctual, and indeed a large literature in evolutionary psychology shows that people derive happiness from being generous," [University of Pennsylvania biology Joshua] Plotkin said. "It's not just in humans. Of course social insects behave this way, but even bacteria and viruses share gene products and behave in ways that can't be described as anything but generous."

Elsewhere, we are told that altruism is just another form of manipulation, which greatly simplifies matters. Indeed, Northeastern University philosophy professor Rory Smead offers a Darwinian explanation of spite (why, counterintuitively, it is adaptive). Yet evolution is also moral, for it punishes the selfish and mean, according to two Michigan State University evolutionary biologists, who claim to disprove an earlier theory popularized in 2012.

We also learn that moral behavior is based on primitive disgust (not rational evaluation); altruism is really a form of sexual display; altruism is really just selfishness; a child must have a selfish motive for saving her sister's life; and why we don't (usually) hurt ourselves to hurt others.

Actually, it is far from clear that altruism selects for survival of selfish genes in humans. In addition to admirable self-sacrifice, there is also "pathological altruism" (often described as co-dependency), a common life- and health-endangering problem. In any event, as Oxford physiologist Denis Noble observes, "selfish genes" have no empirical basis in science. The idea, though "one of the most successful science metaphors ever invented," as David Dobbs tells us at Aeon, does not help us understand how actual genes work.

But never mind genetics, there is still neuroscience. Human brains, we are told, are "hardwired for empathy, friendship" (or they are wired to connect -- as Forbes puts it, "Study: To the Human Brain, Me Is We"). "Our self comes to include the people we feel close to," explains one University of Virginia research team.

This likely is the source of empathy, and part of the evolutionary process, [psychology professor James] Coan reasons.

But if the researchers wish merely to defend the thesis that humans are social rather than solitary, the word "hardwired" and its connotations are comically wrong. The word derives explicitly from devices that do not evolve. If the brain is indeed evolving, then nothing is hard-wired, though some types of experience and behavior may predominate over time and be reflected in brain organization. It is not clear, though, which came first.

A media-friendly approach is to study the animal mind. A cottage industry in this field is the study of primates. The empathy chimpanzees offer is, we are told, key to understanding human engagement. That said, some researcher think that humans are not as empathetic as apes because we are less likely to engage in contagious yawning. But still others say that we can't even predict the level of altruism in apes by their degree of kinship with humans.

"Humans and callitrichid monkeys acted highly altruistically and almost always produced the treats for the other group members. Chimpanzees, one of our closest relatives, however, only did so sporadically." Similarly, most other primate species, including capuchins and macaques, only rarely pulled the lever to give another group member food, if at all -- even though they have considerable cognitive skills.

It depends, these researchers find, on "cooperative breeding." "When our hominin ancestors began to raise their offspring cooperatively, they laid the foundation for both our altruism and our exceptional cognition." Maybe. Could they be cooperative before they were altruistic? On the whole, it is not clear what we can learn from altruism in primates.

Animals do show empathy. But that's part of the puzzle. Consider the monkey who rescued his electrocuted buddy. But then tortoises have been captured on film laboriously turning other upended tortoises back onto their feet.

The nature of the difficulty is apparent when we ask ourselves, what is the tortoise thinking? It is a reptile who cannot right itself, so how does it know enough to right another tortoise? When considering empathy in chimpanzees, we assume, with some justification, that the chimp who helps or shares has mental experiences analogous to those of humans. But if the famously slow-witted tortoise has such experiences as well, then there is not only no "Tree of Intelligence," there seems to be no Tree of Empathy either. Genetic closeness to humans may not have explanatory value for humans, any more than the supposed "selfish gene" does.

For human nature, evolution appears to be an endless well from which any lesson whatever can be drawn. And "evolutionary" explanations need not be informative; they need only be fully naturalist.

 

Darwinism's attempts to explain away why cells take a hit for the team.

Programmed Cell Death Is Vital to Life, but Where'd It Come From?

Ann Gauger January 8, 2015 10:58 AM | 

Not least with today's terrible headlines in mind, death is a disturbing topic. It's something we don't like to talk about, and something we seek to avoid as long as possible. Those who give up their lives for the sake of others are considered heroes, and rightly so. Yet in order for us to develop, to grow from egg to adult, many of our cells have done just that. They gave up their lives for our good.

Scientists call this process of self-sacrifice programmed cell death -- apoptosis is the technical term. It is a program of deliberate self-destruction, much like the auto-destruct program in Star Trek episodes, except in this case, once the program is triggered the process rapidly becomes irreversible. The cell shreds its insides. Its DNA goes through a series of stages that break it down into fragments. The cell's inner structure falls apart and condenses. Then special cells called macrophages clear up the shriveled dead cells.

Cells die for many reasons -- they die to give shape to our fingers and toes, they die to produce our nervous system, they die to make sure our immune system can tell friend from foe. If apoptosis failed in part, the result would be deformity. If it failed entirely, we would all die as embryos. 

So how might such a thing evolve? The benefit of such self-sacrifice can only occur when cells begin to collaborate to make a multicellular organism. One paper proposed such collaboration as something like a mutually assured destruction scenario where two cell types each make molecules the other needs, causing a kind of grudging cooperation between them. Withdrawal of those factors causes cell death, presumably by apoptosis. This scenario is circular. Did cooperation evolve because of cell death, or did cell death evolve because of cooperation? Both would seem to need to be in place at the same time for a stable system to occur.

Another paper argues for the evolution of apoptosis through multiple fortunate episodes of horizontal gene transfer, followed by the creation of a few new protein domains and/or cooption of existing proteins to new functions. They go on to say:

The observations described here emphasize the pivotal role of bacterial-eukaryotic HGT [horizontal gene transfer] in the origin of the eukaryotic PCD system and, by implication, of the eukaryotic multicellularity itself. Indeed, much of the glory of eukaryotic ascension to the ultimate complexity of higher plants and animals might owe to a lucky choice of bacteria with complicated differentiation processes as the primary, and perhaps subsequent symbionts. [Emphasis added.]

Does it make sense to say that eukaryotes fortuitously evolved a way to self-destruct, and then became multicellular, which is presumably where the benefit came in? The first steps would seem to be non-adaptive, of no benefit, in addition to being completely improbable.

I might paraphrase all of this: add just the right ingredients, stir well, then pull a dead rabbit out of your hat.

The Divine law and blood IX:Going mainstream?

Bloodless’ surgery option reveals unexpected benefits

By Sharon Kirkey, Postmedia News

When doctors at a New Jersey hospital pioneered a “bloodless” surgery program for patients who refused blood transfusions on religious grounds, they discovered something totally unexpected: Jehovah’s Witnesses, who would choose death over a transfusion, recovered just as well as transfused patients — and in many cases, even better.

They suffered fewer post-surgery complications, spent less time on mechanical breathing machines and had shorter stays in intensive care.

Recently, doctors from the Cleveland Clinic in Ohio reported that Jehovah’s Witnesses who refused blood transfusions while undergoing cardiac surgery were significantly less likely to need another operation for bleeding compared with non-Witnesses who were transfused. They were also less likely to suffer a post-op heart attack or kidney failure.

Are the Jehovah’s Witnesses onto something?

In cases of massive “bleed outs” from trauma or hemorrhage, or for patients with leukemia or other cancers, blood transfusions can be life-saving.

At the same time, experts say there is remarkably little evidence to show which patients — short of those suddenly losing large amounts of blood — actually benefit from blood transfusions.

In fact, a growing body of research links transfusions with an increased risk of post-surgery infections, cardiac arrest, heart attack, stroke, kidney failure, lung injury, multi-organ failure and death.

Transfused patients spend more time in hospital than those who don’t get blood; they spend more time in intensive care units connected to ventilators; and have a higher risk of acute respiratory distress, where the lungs become saturated with fluid, preventing enough oxygen from getting to the lungs and into the blood.

Studies suggest that up to half of all red-blood-cell transfusions may be unnecessary. Needless transfusions not only waste blood, they expose patients to risks — including potentially life-threatening human errors that are occurring at every step in the transfusion chain.

Three decades after Canada’s catastrophic tainted-blood tragedy left 2,000 people infected with HIV and another 30,000 with hepatitis C, the greatest threat to patients today isn’t the risk of contracting an infectious disease from blood, experts now say.

It’s getting blood they don’t need.

Overused medical procedure?

From ancient times to the late 19th century, sickness was treated by blood loss: using lances or leeches to bleed the body of suspected diseases that caused “bad” blood.

Today, we call blood the “gift of life.” The belief that blood is almost a magical cure is still held by many.

“In the minds of many people, blood is life, and giving people blood must help life,” says Dr. Jacques Lacroix, a professor of pediatrics at the University of Montreal and a national and international pioneer in pediatric critical care and research.

“But it does not work like that.”

In fact, transfusions have been identified by the American Medical Association as among the top five overused procedures in medicine.

In Canada, about 850,000 units of red blood cells, and 102,000 doses of platelets, were transfused into patients outside Quebec in 2011-2012, according to estimates compiled by the Canadian Blood Services for Postmedia News. (Hema-Quebec, which runs the province’s blood system, collected 252,340 units of blood from donors in 2011-2012; more than 526,000 blood products were shipped to hospitals.)

Canadian researchers have led the world in showing that patients benefit from more restrictive blood use.  But, there is no single, unified national system to determine how much of the blood distributed by the Canadian Blood Services is actually transfused, who gets it and whether it’s being given for the right reasons.

Studies suggest that, even when patients have the same underlying condition, the same surgery and the same blood loss, transfusion rates vary widely from hospital to hospital for the same operation.

For example, a review of more than 8,000 patients who underwent cardiac surgery in British Columbia between 2008 and 2010 found that the proportion of patients who received red-blood-cell transfusions ranged from 35 to 66 per cent.

A provincewide audit of Ontario hospitals published in May concluded that nearly one in three transfusions of frozen plasma — the liquid portion of blood that contains clotting factors to help control bleeding during surgery — was unnecessary.

In Calgary, knee replacement patients are being transfused at rates ranging from two per cent of patients to 25 per cent, depending on the surgeon.

Many transfusions don’t meet even minimum published guidelines, experts say. Many patients receive not one, but multiple units of blood, increasing their risk of fluid overload, where the extra blood overwhelms the heart’s ability to pump it through the body. Transfusion-related circulatory overload is one of the leading causes of transfusion-related death.

In some areas of medicine, including cardiac surgery, no clear consensus exists on when patients should be transfused.

“What we are sure of, however, is that there is a huge variation in transfusion rates across Canada for cardiac surgery patients of the same risk profile, and this is very difficult to explain,” says Dr. Fraser Rubens, a cardiac surgeon at the University of Ottawa Heart Institute.

Limiting the use of blood

As concern mounts over the dangers of unnecessary transfusions, hospitals have begun using strategies to reduce the use of blood.

For example:

• Blood draining out from under surgical wounds is being siphoned off, re-processed and then re-infused back into the patient.

• Surgeons are using drugs to prevent bleeding and improve blood clotting.

• Surgeons are operating through laparoscopes and other minimally invasive tools to reduce bleeding from large surgical wounds.

• Patients are being screened and treated for anemia with supplements or drugs that boost the bone marrow to produce red blood cells before they get into the operating room.

The variability in transfusion rates is slowly falling. But doctors have been slow to adapt. “The biggest challenge is trying to change the behaviour of physicians,” says Dr. Alan Tinmouth, a hematologist and scientist at the Ottawa Hospital Research Institute. “People are being transfused at hemoglobin levels higher than they need to be.”

Many doctors remain unconvinced of the potential dangers of transfusions. None of the studies suggesting increased risks of harm prove cause-and-effect, just an association, they point out. What’s more, patients who are transfused tend to be sicker to begin with, so it’s no surprise that they don’t recover as well as non-transfused patients, they argue.

But Dr. Paul Marik says numerous studies have shown that the more blood given, the worse the outcome.

In a widely cited study published in 2008, Marik analyzed 45 studies involving nearly 300,000 patients. In 42 of those studies, the risks of red-blood-cell transfusions outweighed the benefits. Transfused patients were twice as likely to develop infections, multi-organ failure and acute respiratory distress than the non-transfused.

Critics of his conclusions say many of the older studies were done before white cells were filtered out of whole-blood donations. White cells in the “host” body help fight disease and infection. But when they’re put into someone else, they can suppress the immune system.

More recent studies have shown that transfusion-related reactions have fallen since blood suppliers began washing white blood cells from blood. However, Dr. Aryeh Shander, clinical professor of anesthesiology, medicine and surgery at Mount Sinai School of Medicine in New York, says that while there has been an unquestionable reduction in fever rates, “the rest is debated.”

Shander helped create the bloodless medicine and surgery program at Englewood Hospital and Medical Center in Englewood, New Jersey. He says that “old habits die hard” and that too many doctors believe “something bad will happen” if patients don’t have a certain volume of blood in their system.

Hemoglobin transfusions can be risky

The biggest driver of red blood-cell transfusions is hemoglobin, the protein in red blood cells that ferries oxygen from the lungs to tissues and cells throughout the body. Too little hemoglobin, and the person becomes anemic.

Red blood cells are frequently transfused during cardiac surgery, prostate surgery, joint replacements and in patients bleeding from their intestinal tracts.

But, once removed from the body, red cells undergo changes in their shape and function. Their membranes deteriorate; some cells burst, releasing free hemoglobin, which mops up nitric oxide, the chemical that helps blood vessels relax. There are now growing concerns that “older” red cells stored for longer than a few weeks lose some of their ability to transport oxygen — the very reason they’re transfused. In Canada, red cells are stored for up to 42 days.

Dr. Paul Hebert, Critical Care Physician at The Ottawa Hospital on July 8, 2013, led a groundbreaking study which found that ICU patients who were transfused when they were only mildly anemic were more likely to die than patients who weren’t transfused. (Chris Roussakis / Postmedia News)

When he was in medical school, Ottawa critical care specialist Dr. Paul Hebert, whose research has transformed transfusion practices worldwide, was taught that seriously ill patients need a high level of hemoglobin to keep diseased or damaged tissues alive. So ingrained was this belief that anesthesiologists and surgeons routinely began transfusing surgery patients if their hemoglobin dipped below a certain number (100 grams per litre of blood.)

In a landmark paper published in the New England Journal of Medicine, Hebert and his team found that patients who were only mildly below that hemoglobin cutoff, but who were treated aggressively with transfused blood nonetheless, were more likely to die, and had higher rates of organ failure, than patients whose doctors held back until their hemoglobin fell to lower levels.

“We found that, if you give less blood, you do better,” Hebert said. “We think that’s because many of the patients didn’t need it in the first place.”

In a study published in January 2013, Hebert and co-authors reviewed 19 trials involving more than 6,000 patients that compared higher versus lower hemoglobin thresholds in red-blood-cell transfusions. They found that patients could be transfused at hemoglobin levels of 70 or 80 grams per litre of blood without putting them at any increased risk for major complications such as pneumonia, stroke, infection, or death.

If doctors were to use the lower thresholds, “I think you can reduce blood use in many settings by at least half,” said lead author Dr. Jeffrey Carson, chief of the division of general internal medicine at Rutgers Robert Wood Johnson Medical School in New Brunswick, New Jersey.

A recent review of blood transfusions at three Ontario hospitals found that the pre-transfusion hemoglobin levels were higher than the recommended thresholds for many patients.

Some transfusion rates have been falling since the province established a network of blood transfusion co-ordinators in 25 hospitals. A major thrust of the program is to treat patients with anemia — low hemoglobin — before surgery “so that we avoid having to transfuse them when they bleed,” said Dr. John Freedman, medical director of the program and professor emeritus at the University of Toronto.

British Columbia created the first transfusion registry in Canada in 1999; it remains one of the largest in North America. The database tracks every unit of blood that gets transfused into someone in B.C or the Yukon.

Within the year, The Ottawa Hospital hopes to have a computerized system in place to capture where blood is going, which patients are being transfused and their hemoglobin levels at transfusion.

According to the Canadian Blood Services, Canada is at the lower end of blood use worldwide, and experts say it would be dangerous to attempt to cut transfusion rates to near zero. As well, demand for blood is expected to grow as the population ages, because older people use more blood. While Jehovah’s Witnesses have taught doctors that the body can compensate for extraordinarily low levels of hemoglobin, levels that are too low mean the cells and tissues in the brain and other vital organs become starved of oxygen.

Hebert has watched Jehovah’s Witnesses die for refusing to be transfused, an experience that leaves the medical team feeling helpless. “But you can’t force your values on someone else,” he says.

Hebert says more research and education is needed to help doctors decide how long they can safely wait before ordering blood, how much blood they should give and when to hold off giving any blood at all.

“The problem is that we don’t have the data,” Hebert said. “In many cases, we just don’t know.”

By the numbers

900,000 – Average number of units of blood collected each year in Canada, outside Quebec. (Hema-Quebec, which runs the province’s blood system, collected 252,340 units of blood from donors in 2011/2012).

850,000 – Estimated units of red blood cells transfused into patients in Canada in 2011/2012.

More than 2.5 million – Number of bottles of blood collected in Canada during Second World War to help soldiers and war victims.

5 – Average number of litres of blood in a person’s body.

450 milliliters – Amount of blood that goes into a single donation. Though it is frequently referred to as a “pint,” a blood donation is 450 mL rather than the 570 mL in a pint. The human body begins replenishing the lost blood within hours, and finishes the job within 56 days.

20,000 – Number of blood clinics run by Canadian Blood Services each year.

42 days – Maximum shelf life for red blood cells collected through blood donations. Most blood is sent to hospitals within a week. Platelets have only a five-day shelf life.

One – Number of hours, on average, it takes to donate blood.

17 – Minimum legal age for donating blood in Canada.

7  – Number of times a year a healthy person can donate blood (i.e. every 56 days).

Every 60 seconds – How often, on average, someone in Canada receives blood or a blood product.

4 – Number of days after which the supply of blood products for high-demand blood groups would run out if Canadians stopped donating blood.

3 – Number of lives that can be saved with one donation of blood. Whole blood donations are separated into red cells, platelets and plasma. Each component can be given to a different person.

52 per cent – Proportion of Canadians who say they or a family member have needed blood or blood products for surgery or for medical treatment.

One in 10 – Number of people admitted to hospital who receive blood.

54 per cent – Proportion of Canadians eligible to donate blood.

3.7 per cent – Proportion of Canadians who actually give blood.

One in three – Number of Canadians who do not know their blood type.

Two – Average number of units of blood transfused for hip replacement surgery.

50 – Average units of blood transfused to save the life of a car-crash victim.

2,000 – Number of Canadians infected with HIV from donated blood.

30,000 – Number of Canadians infected with hepatitis C.

1 in 8 million donations – Estimated risk of HIV today.

1 in 6.7 million donations – Estimated risk of hepatitis C.

1 in 1.7 million donations – Estimated risk of hepatitis B,

Sources: Canadian Blood Services, American Red Cross, Hema-Quebec

A brief history of blood

400 BC – Hippocrates postulates that the body is comprised of four “humours” — blood, phlegm, black and yellow bile — and that their imbalance causes disease.

1492 – Earliest recorded transfusion: As a remedy for a stroke suffered by Pope Innocent VIII, his doctor advises a blood transfusion. The blood of four young adults is transferred to the Pope. Donors and patient later all die.

1628 – British physician William Harvey discovers the circulation of blood.

1665 – First recorded successful blood transfusion. English physician Richard Lower keeps dog alive by transfusing blood from other dogs.

1667 – French physician Jean-Baptiste Denis transfuses blood from sheep into a patient. The patient survives.

1818 – British obstetrician James Blundell performs the first successful transfusion of human blood to a woman hemorrhaging after childbirth, using the woman’s husband as a donor.

1897 – Bram Stoker’s classic horror novel Dracula, about a blood-sucking being, is published.

1901 – Austrian physician Karl Landsteiner discovers the first three human blood groups – A, B and C (C later changed to O). AB, the fourth type is discovered two years later; the Rh blood group is discovered in 1939-1940.

1926 – The British Red Cross institutes the first human blood transfusion service in the world.

1945 – Canadians start giving blood to hospitals.

1947 – Canada establishes a national blood transfusion service; the first blood centre opens in Vancouver. By 1961, Canada has 16 blood centres serving every region of the country.

July 1981 – First cluster of AIDS identified in homosexuals in Los Angeles.

July 1982 – AIDS identified in hemophiliacs.

December 1982 – AIDS identified in blood transfusion recipients.

1983 – French virologist Luc Montagnier isolates the virus that causes AIDS. The Canadian Red Cross Society prohibits blood donations from men who have sex with men.

November 1985 – Red Cross starts screening all blood for HIV.

1987 – Guidelines in the U.S. and Canada encourage people who had transfusions to be tested for HIV.

October 1993 – The federal government authorizes the creation of a Commission of Inquiry on the Blood System in Canada. Justice Horace Krever is appointed as commissioner.

November 1997 – Justice Horace Krever releases his voluminous report on the tainted-blood scandal.

September 1998 – Canadian Red Cross gets out of the blood business, transferring assets to the Canadian Blood Services and Hema-Quebec.

1999 – Canadian Blood Services introduces its first deferral policy for Creutzfeldt-Jakob disease (variant CJD), the human equivalent of “mad cow” disease and announces that people can no longer donate blood if they have spent six months or more in the United Kingdom since 1980.

May 2013 – Canadian Blood Services loosens restrictions on blood donations from men who have sex with men, saying it will now accept donations from men who haven’t had sex with another man within the last five years. Before the change, men who had had sex with another man at any time since 1977 (the beginning of the AIDS epidemic in the U.S.) were turned away.

Sources: U.K. Blood Transfusion & Tissue Transplantation Services; AABB; Canadian Blood Services

Some more unsettled science.

Selection and Speciation: Why Darwinism Is False

Jonathan Wells May 15, 2009 10:00 AM

 Coyne writes that Darwin "had little direct evidence for selection acting in natural populations." Actually, Darwin had no direct evidence for natural selection; the best he could do in The Origin of Species was "give one or two imaginary illustrations." It wasn't until a century later that Bernard Kettlewell provided what he called "Darwin's missing evidence" for natural selection -- a shift in the proportion of light- and dark-colored peppered moths that Kettlewell attributed to camouflage and bird predation.⁴⁰

Since then, biologists have found lots of direct evidence for natural selection. Coyne describes some of it, including an increase in average beak depth of finches on the Galápagos Islands and a change in flowering time in wild mustard plants in Southern California -- both due to drought. Like Darwin, Coyne also compares natural selection to the artificial selection used in plant and animal breeding.

But these examples of selection -- natural as well as artificial -- involve only minor changes within existing species. Breeders were familiar with such changes before 1859, which is why Darwin did not write a book titled How Existing Species Change Over Time; he wrote a book titled The Origin of Species by Means of Natural Selection. "Darwin called his great work On the Origin of Species," wrote Harvard evolutionary biologist Ernst Mayr in 1982, "for he was fully conscious of the fact that the change from one species into another was the most fundamental problem of evolution." Yet, Mayr had written earlier, "Darwin failed to solve the problem indicated by the title of his work." In 1997, evolutionary biologist Keith Stewart Thomson wrote: "A matter of unfinished business for biologists is the identification of evolution's smoking gun," and "the smoking gun of evolution is speciation, not local adaptation and differentiation of populations." Before Darwin, the consensus was that species can vary only within certain limits; indeed, centuries of artificial selection had seemingly demonstrated such limits experimentally. "Darwin had to show that the limits could be broken," wrote Thomson, "so do we."⁴¹

In 2004, Coyne and H. Allen Orr published a detailed book titled Speciation, in which they noted that biologists have not been able to agree on a definition of "species" because no single definition fits every case. For example, a definition applicable to living, sexually reproducing organisms might make no sense when applied to fossils or bacteria. In fact, there are more than 25 definitions of "species." What definition is best? Coyne and Orr argued that, "when deciding on a species concept, one should first identify the nature of one's 'species problem,' and then choose the concept best at solving that problem." Like most other Darwinists, Coyne and Orr favor Ernst Mayr's "biological species concept" (BSC), according to which "species are groups of interbreeding natural populations that are reproductively isolated from other such groups." In Why Evolution Is True, Coyne explains that the biological species concept is "the one that evolutionists prefer when studying speciation, because it gets you to the heart of the evolutionary question. Under the BSC, if you can explain how reproductive barriers evolve, you've explained the origin of species."⁴²

Theoretically, reproductive barriers arise when geographically separated populations diverge genetically. But Coyne describes five "cases of real-time speciation" that involve a different mechanism: chromosome doubling, or "polyploidy."⁴³ This usually follows hybridization between two existing plant species. Most hybrids are sterile because their mismatched chromosomes can't separate properly to produce fertile pollen and ovaries; occasionally, however, the chromosomes in a hybrid spontaneously double, producing two perfectly matched sets and making reproduction possible. The result is a fertile plant that is reproductively isolated from the two parents -- a new species, according to the BSC.

But speciation by polyploidy ("secondary speciation") has been observed only in plants. It does not provide evidence for Darwin's theory that species originate through natural selection, nor for the neo-Darwinian theory of speciation by geographic separation and genetic divergence. Indeed, according to evolutionary biologist Douglas J. Futuyma, polyploidy "does not confer major new morphological characteristics... [and] does not cause the evolution of new genera" or higher levels in the biological hierarchy.⁴⁴

So secondary speciation does not solve Darwin's problem. Only primary speciation -- the splitting of one species into two by natural selection -- would be capable of producing the branching-tree pattern of Darwinian evolution. But no one has ever observed primary speciation. Evolution's smoking gun has never been found.⁴⁵

Or has it?

In Why Evolution Is True, Coyne claims that primary speciation was observed in an experiment reported in 1998. Curiously, Coyne did not mention it in the 2004 book he co-authored with Orr, but his 2009 account of it is worth quoting in full:

We can even see the origin of a new, ecologically diverse bacterial species, all within a single laboratory flask. Paul Rainey and his colleagues at Oxford University placed a strain of the bacteria Pseudomonas fluorescens in a small vessel containing nutrient broth, and simply watched it. (It's surprising but true that such a vessel actually contains diverse environments. Oxygen concentration, for example, is highest on the top and lowest on the bottom.) Within ten days--no more than a few hundred generations--the ancestral free-floating 'smooth' bacterium had evolved into two additional forms occupying different parts of the beaker. One, called 'wrinkly spreader,' formed a mat on top of the broth. The other, called 'fuzzy spreader,' formed a carpet on the bottom. The smooth ancestral type persisted in the liquid environment in the middle. Each of the two new forms was genetically different from the ancestor, having evolved through mutation and natural selection to reproduce best in their respective environments. Here, then, is not only evolution but speciation occurring in the lab: the ancestral form produced, and coexisted with, two ecologically different descendants, and in bacteria such forms are considered distinct species. Over a very short time, natural selection in Pseudomonas yielded a small-scale 'adaptive radiation,' the equivalent of how animals or plants form species when they encounter new environments on an oceanic island.⁴⁶

But Coyne omits the fact that when the ecologically different forms were placed back into the same environment, they "suffered a rapid loss of diversity," according to Rainey. In bacteria, an ecologically distinct population (called an "ecotype") may constitute a separate species, but only if the distinction is permanent. As evolutionary microbiologist Frederick Cohan wrote in 2002, species in bacteria "are ecologically distinct from one another; and they are irreversibly separate."⁴⁷ The rapid reversal of ecological distinctions when the bacterial populations in Rainey's experiment were put back into the same environment refutes Coyne's claim that the experiment demonstrated the origin of a new species.

Exaggerating the evidence to prop up Darwinism is not new. In the Galápagos finches, average beak depth reverted to normal after the drought ended. There was no net evolution, much less speciation. Yet Coyne writes in Why Evolution Is True that "everything we require of evolution by natural selection was amply documented" by the finch studies. Since scientific theories stand or fall on the evidence, Coyne's tendency to exaggerate the evidence does not speak well for the theory he is defending. When a 1999 booklet published by The U. S. National Academy of Sciences called the change in finch beaks "a particularly compelling example of speciation," Berkeley law professor and Darwin critic Phillip E. Johnson wrote in The Wall Street Journal: "When our leading scientists have to resort to the sort of distortion that would land a stock promoter in jail, you know they are in trouble."⁴⁸

So there are observed instances of secondary speciation -- which is not what Darwinism needs -- but no observed instances of primary speciation, not even in bacteria. British bacteriologist Alan H. Linton looked for confirmed reports of primary speciation and concluded in 2001: "None exists in the literature claiming that one species has been shown to evolve into another. Bacteria, the simplest form of independent life, are ideal for this kind of study, with generation times of twenty to thirty minutes, and populations achieved after eighteen hours. But throughout 150 years of the science of bacteriology, there is no evidence that one species of bacteria has changed into another."⁴⁹

Notes

⁴⁰ Coyne, Why Evolution Is True, p. 116.

Darwin, The Origin of Species, Chapter IV (p. 70). Available online (2009) here.

H. B. D. Kettlewell, "Darwin's Missing Evidence," Scientific American 200 (March, 1959): 48-53.

⁴¹ Ernst Mayr, The Growth of Biological Thought (Cambridge, MA: Harvard University Press, 1982), p. 403.

Ernst Mayr, Populations, Species and Evolution (Cambridge, MA: Harvard University Press, 1963), p. 10.

Keith Stewart Thomson, "Natural Selection and Evolution's Smoking Gun," American Scientist 85 (1997): 516-518.

⁴² Jerry A. Coyne & H. Allen Orr, Speciation (Sunderland, MA: Sinauer Associates, 2004), p. 25-39.

Coyne, Why Evolution Is True, p. 174.

⁴³ Coyne, Why Evolution Is True, p. 188.

⁴⁴ Douglas J. Futuyma, Evolution (Sunderland, MA: Sinauer Associates, 2005), p. 398.

⁴⁵ Wells, The Politically Incorrect Guide to Darwinism and Intelligent Design, Chapter Five ("The Ultimate Missing Link"), pp. 49-59.

⁴⁶ Coyne, Why Evolution Is True, pp. 129-130.

⁴⁷ Paul B. Rainey & Michael Travisano. "Adaptive radiation in a heterogeneous environment,"Nature 394 (1998): 69-72.

Frederick M. Cohan, "What Are Bacterial Species?" Annual Review of Microbiology 56 (2002): 457-482. Available online (2009) here.

⁴⁸ Coyne, Why Evolution Is True, p. 134.

National Academy of Sciences, Science and Creationism: A View from the National Academy of Sciences, Second edition (Washington, DC: National Academy of Sciences Press, 1999), Chapter on "Evidence Supporting Biological Evolution," p. 10. Available online (2009) here.

Phillip E. Johnson, "The Church of Darwin," The Wall Street Journal (August 16, 1999): A14. Available online (2009) here.

⁴⁹ Alan H. Linton, "Scant Search for the Maker," The Times Higher Education Supplement (April 20, 2001), Book Section, p. 29.