Big Pharma and the Cost of Drugs

James Surowiecki provided some thoughts on the financial condition of the drug industry in an article in The New Yorker: Biotech’s Hard Bargain. He points out that stocks in the biotech sector rose more than 120% over the last two years before seeing a downward correction of about 20%. He attributes much of that market drop to the appearance of a new drug with great promise for the ill, but perhaps greater promise for investors.

"Hepatitis C affects 3.2 million Americans; untreated, it leads to scarring of the liver and to liver cancer. Until now, the best treatments cured only about half of patients and often had debilitating side effects. But in December the F.D.A. approved the first in a new wave of hep-C drugs, Gilead’s Sovaldi. This is huge news—not just in medicine but on Wall Street. "

"Sovaldi can cure ninety per cent of patients in three to six months, with only minor side effects. There’s just one catch: a single dose of the drug costs a thousand dollars, which means that a full, twelve-week course of treatment comes to more than eighty grand."

To put this in perspective, the treatment of 3 million people at $80,000 per pop will run up a bill of $240 billion. Can such an extraction from the public purse be justified in any way?

"Investors love drug companies in part because they often have tremendous pricing power. Drugs designed to fight rare diseases routinely cost two or three hundred thousand dollars; cancer drugs often cost a hundred grand. And, whereas product prices in most industries drop over time, pharmaceuticals actually get more expensive. The price of the anti-leukemia drug Gleevec, for instance, has tripled since 2001. And, across the board, drug prices rise much faster than inflation."

"….prices for brand-name, patented drugs aren’t really set in a free market. The people taking the drugs aren’t paying most of the cost, which makes them less price-sensitive, and the bargaining power of those who do foot the bill is limited. Insurers have to cover drugs that work well; the economists Darius Lakdawalla and Wesley Yin recently found that even big insurers had "virtually zero" ability to drive a hard bargain when it comes to drugs with no real equivalents. And the biggest buyer in the drug market—the federal government—is prohibited from bargaining for lower prices for Medicare, and from refusing to pay for drugs on the basis of cost. In short, if you invent a drug that doctors think is necessary, you have enormous leeway to charge what you will."

When one asks why drugs cost so much, the stock reply is that the revenue flow is required in order to cover the costs of research and development (R&D). Let us pause for a moment and consider how big pharma actually uses its money.

The World Health Organization (WHO) provided this opinion on the state of affairs with respect to the pharmaceutical industry:

"As a result of this pressure to maintain sales, there is now, in WHO's words, ‘an inherent conflict of interest between the legitimate business goals of manufacturers and the social, medical and economic needs of providers and the public to select and use drugs in the most rational way’. This is particularly true where drugs companies are the main source of information as to which products are most effective."

This bit of data was also provided:

"The 10 largest drugs companies control over one-third of this market, several with sales of more than US$10 billion a year and profit margins of about 30%....Companies currently spend one-third of all sales revenue on marketing their products - roughly twice what they spend on research and development."

By this reckoning, R&D costs can’t be more than about 15-20% of revenue. And how could marketing costs conceivably be twice as high?

Doctors seem to change their habits slowly. There is inertia involved in accepting the efficacy of a new drug, and there is similarly inertia in switching away from a drug once accepted. It has been estimated that it takes about 10 years for new medical knowledge to wend its way throughout the medical profession. This source provided this extreme example:

"Physicians have been indefensibly slow to adopt guidelines that would potentially prevent premature deaths or harm. One egregious example is the estimated 100,000 heart failure patients that died prematurely each year in the late 1990s because they did not receive beta-blockers. The efficacy of beta-blockers was established by a study published in the JAMA in 1982."

Drug companies spend enormous amounts of marketing money convincing doctors to use their products because time is money to them. To fully take advantage of their pricing leverage they must have their drugs prescribed as soon as possible after hitting the market. Waiting around for word-of-mouth recommendations or dispersion of published articles is too slow and too risky a process.

There is a significant return on a successful marketing campaign. Once a significant base of drug prescribers is established, the drug company can go ahead and raise the prices as much as it wants with little fear that the doctors will notice or care.

Robert Langreth provided an example of how this pricing strategy works in an article in Bloomberg Businessweek: Big Pharma’s Favorite Prescription: Higher Prices.

"New branded rivals in a market sometimes provide cover for older players to boost prices. For example, prescriptions for Biogen Idec’s multiple sclerosis drug Avonex have slowly declined in the U.S. in recent years because of competition. At the same time, Avonex’s wholesale price has risen 147　percent to $1,363.50 per injection this year from $552.19 in late 2007…."

"Largely because of price increases, Avonex’s U.S. sales have grown 75　percent since 2007, reaching $1.9　billion last year."

So, once a market is established it is little affected by price. If sales fall, just raise the price to maintain or increase the cash flow.

Mariana Mazzucato provides more insight into drug companies and their finances in her book The Entrepreneurial State: Debunking Public vs. Private Sector Myths.

"The ex-editor of the New England Journal of Medicine, Marcia Angell, has argued forcefully that while private pharmaceutical companies justify their exorbitantly high prices by saying they need to cover their high R&D costs, in fact most of the really ‘innovative’ new drugs….come from publicly funded laboratories. Private pharma has focused more on ‘me too’ drugs (slight variations of existing ones) and the development (including clinical trials) and marketing side of the business."

"….in recent years, CEOs of large pharma companies have admitted that their decision to downsize—or in some cases eliminate—their R&D labs is due to their recognition that in the ‘open model’ of innovation most of their research is obtained by small biotech firms or public labs."

Big pharma can use its immense wealth to purchase the best of little pharma and make a small company quite wealthy, while it makes the big money in commercializing the drug.

In dealing with public labs, they barely even have to pay for the drug. Mazzucato provides this example:

"After taking on most of the R&D bill, the state often gives away the outputs at a rock-bottom rate. For example, Taxol, the cancer drug discovered by the National Institutes of Health (HIH), is sold by Bristol-Myers Squibb for $20,000 per year’s dose, 20 times the manufacturing cost. Yet, the company pays the NIH just 0.5 per cent in royalties for the drug. In most other cases, nothing at all is paid in royalties. It is simply assumed that the public investment is meant to help create profits for the firms in question…."

Mazzucato also provides us with another example of how big pharma uses its wealth in ways that have nothing to do with R&D. It seems that buying back shares of their own company in order to make short-term market moves is more important to the drug companies than R&D.

"….it cannot be denied that at the same time that private pharma companies have been reducing the R of R&D, they have been increasing the amount of funds used to repurchase their own shares—a strategy used to boost their stock price, which affects the price of stock options and executive pay linked to such options. For example, in 2011, along with $6.2 billion paid in dividends, Pfizer repurchased $9 billion in stock, equivalent to 90 per cent of its net income and 99 per cent of its R&D expenditures…."

Surowiecki wonders if the case of Sovaldi and its price may have been that one step too far. The point at which the public realizes that these prices and the associated profits are no longer sustainable and action must be taken.

"Biotech, in other words, may become the victim of its own success: the bigger the profits, the bigger the likelihood of regulation."

However, he is not optimistic—at least not in the near term.

"You might think that this prospect would encourage companies to be more cautious. But, if you assume that price controls are coming, the rational play is to squeeze out all the profits you can now. The uproar over Sovaldi may, somewhere down the line, help contain drug prices. But in the short run it could well make drugs even more expensive. And that’s what you call a serious side effect."
　
Marcia Angell is the author of The Truth About the Drug Companies: How They Deceive Us and What to Do About It.

How to Kill the Ocean—and Life as We Know It

The disputes about global warming and climate change seem to center on whether or not the effects are being caused by human activities. The answer to that should be obvious, but even the doubters should be concerned because whatever the reason, things could go very badly for humanity—and all other life forms.

Somewhat lost in the discussion is the status of our oceans. We are told that rising sea levels will inundate many of the coastal areas where much of our population resides. However, that could only be the beginning.

Sylvia A. Earle provides some perspective on our relationship with the oceans.

"There are many reasons for despair about the future of the ocean—and therefore, of humankind. The ocean is, in effect, our life-support system, driving climate and weather, governing the water cycle, stabilizing temperature, generating most of the oxygen in the atmosphere, taking up much of the carbon dioxide, shaping planetary chemistry. If the ocean is in trouble, so are we."

She also provides a status report.

"In the middle of the twentieth century, it seemed the ocean was too vast, too resilient, for humans to cause any harm. Now we know otherwise. Since the 1960s, 90 percent of many sought-after fish are gone, including sharks, tuna, swordfish, marlin, and many others. Half the coral reefs, mangrove forests, and seagrass meadows have been destroyed or are in a state of sharp decline. Hundreds of ‘dead zones’ have formed in coastal waters, while phytoplankton has declined globally by as much as 40 percent. Excess carbon dioxide released into the atmosphere is causing the ocean to become more acidic. The increase in jellyfish blooms is one of the many signs signaling a sea change."

These quotes were from Earle’s Introduction to Lisa-ann Gershwin’s book Stung!: On Jellyfish Blooms and the Future of the Ocean. We will use this source for information on relevant oceanic dynamics.

Gershwin’s view of the future is appropriately pessimistic.

"A great many books—some of which are fascinating reads—have been written on climate change, overfishing, and the pollution of our ecosystems. But there is a pattern to these books that I believe is not completely accurate, and is perhaps somewhat misleading. They leave the reader with the feeling that if we would just stop polluting, everything would be okay—that if we would just stop overfishing, the oceans would return to normal. These ideas sound good, but are not what we observe actually taking place."

The damage we do can have primary effects that we notice, but there are many secondary effects that are less obvious.

"When we think of overfishing, we forget that the warming waters of climate change are reducing the dissolved oxygen, making it harder for fish to respire and survive, and thus further contributing to the loss of fish. When we think of pollution, we think of smelly nasty corners of marinas, or beer cans and plastic drink bottles washed up on beaches, but we don’t think about the heavy metals or pesticide residues accumulating in our food supply and in our own bodies as a result….or about the excess nutrients flowing into estuaries and bays, creating vast dead zones…."

Gershwin now believes that we have passed a point of no return and the changes we have caused are irreversible.

"I now sincerely believe that it is only a matter of time before the oceans as we know them and need them to be become very different places indeed. No coral reefs teeming with life. No more mighty whales or wobbling penguins. No lobsters or oysters. Sushi without fish."

"In their place we shall see blue-green algae, emerald green algae, golden algae, flashing blue algae, red tides, brown tides, and jellyfish. Lots of jellyfish."
　
She compares our impacts on ocean life to those of the great geophysical changes that have occurred in the long history of the earth.

"Throughout the history of life on earth, major macroevolutionary events, such as mass extinctions and periods on intense evolutionary diversification have been linked to global-scale changes in environmental conditions….Today’s overfishing, pollution, and greenhouse gas emissions are comparable to the intense global warming, acidification, hypoxia [low oxygen], and mass extinctions throughout history….all at once."

Lest that last sentence be left to seem a bit overwrought, let’s pursue continued pollution and growing hypoxia to a final state and see what fate might possibly await us.

The continued increase in carbon dioxide in the atmosphere will cause the temperature to rise and will increase the amount of carbon dioxide absorbed into the ocean. This latter concentration will increase the acidity of the ocean and one of the effects will be the disappearance of things like lobsters and oysters as they will no longer be able to maintain their structures. This will take some time, but the effects are already measurable in terms of structural integrity of their shells.

The overall change in temperature of the oceans, felt mainly at the important surface layer, will continue to lower the oxygen content in the water. The continued pollution of our waterways, mostly with agricultural runoff containing fertilizers and animal waste, create vast dead zones—regions where oxygen is so depleted that essentially no life can be maintained.

"Eutrophication, an excess of nutrients in the ecosystem, occurs when these hypernutrified waters draining off the land are warmer and less salty than the seawater they are discharged into….This meeting creates stratification in the water column where the cooler, saltier, denser water stays on the bottom, and the warmer, fresher water floats on top."

This hypernutrified surface layer produces an overabundance of sea life, more than can be consumed. The result is that unconsumed phytoplankton and fecal matter sink to the bottom where aerobic bacteria consume them and use valuable oxygen in the process.

"Because the saltier layer is trapped below the surface layer and unable to touch air, the oxygen dissolving from the air cannot reach the bottom layer. The combination of stratification and decomposing organic matter create a zone of hypoxia (low oxygen) or anoxia (no oxygen) just above the seabed….Those creatures that can leave—those that can’t leave suffocate."

"As it worsens, the hypoxic area becomes one of the notorious ‘black bottoms’ with foul smelling sediments….Hypoxia leads to anoxia which leads to toxic hydrogen sulfide."

These dead zones that are created have a mechanism that exacerbates the situation and creates even greater nutrient growth and an increase in the size of the dead zone.

"Hypoxic bottom-water conditions cause seafloor sediments to release dissolved inorganic phosphorus. In the Baltic, the volume of phosphorus released from sediments is an order of magnitude larger than the amount flowing in from rivers. This stimulates a positive feedback cycle of phytoplankton blooms that drive hypoxia."

And then there is this final observation about dead zones:

"There are no known examples of recovery of large ecosystems from persistent hypoxia or anoxia….Once initiated, the low-oxygen condition appears to be permanent, even in the seasonal cases."

This is all consistent with the notion that we are causing irreversible damage to our oceans and our sea life. The expectation is that our coastlines will form a continuous boundary layer along the shores of our continents.

Wikipedia provides this information on dead zones.

"In March 2004, when the recently established UN Environment Programme published its first Global Environment Outlook Year Book (GEO Year Book 2003), it reported 146 dead zones in the world's oceans where marine life could not be supported due to depleted oxygen levels. Some of these were as small as a square kilometre (0.4 square miles), but the largest dead zone covered 70,000 square kilometres (27,000 square miles). A 2008 study counted 405 dead zones worldwide."

This chart, where red circles indicate the location and size of many of the dead zones, was also provided.

Recall that Gershwin told us that the ultimate result of anoxia was the production of the poisonous gas hydrogen sulfide. There are species of anaerobic bacteria that thrive in anoxic conditions. From Wikipedia:


"Sulfate-reducing bacteria can be traced back to 3.5 billion years ago and are considered to be among the oldest forms of microorganisms, having contributed to the sulfur cycle soon after life emerged on Earth."

"Sulfate occurs widely in seawater, sediment, or water rich in decaying organic material. Sulfate-reducing bacteria are common in anaerobic environments where they aid in the degradation of organic materials."

"The toxic hydrogen sulfide is a waste product of sulfate-reducing bacteria; its rotten egg odor is often a marker for the presence of sulfate-reducing bacteria in nature. Sulfate-reducing bacteria are responsible for the sulfurous odors of salt marshes and mud flats."

Gershwin also associated the term "mass extinction" with our current trajectory. Was that a bit of a reach? Perhaps not. Consider what is known of the greatest of the mass extinctions known as the Great Dying. Again from Wikipedia:

"It is the Earth's most severe known extinction event, with up to 96% of all marine species and 70% of terrestrial vertebrate species becoming extinct. It is the only known mass extinction of insects."

That event occurred about 250 million years ago. The geological record from that period contains evidence of widespread ocean anoxia and euxinia (the presence of hydrogen sulfide).

"A severe anoxic event at the end of the Permian would have allowed sulfate-reducing bacteria to thrive, causing the production of large amounts of hydrogen sulfide in the anoxic ocean. Upwelling of this water may have released massive hydrogen sulfide emissions into the atmosphere. This would poison terrestrial plants and animals, as well as severely weaken the ozone layer, exposing much of the life that remained to fatal levels of UV radiation. Indeed, biomarker evidence for anaerobic photosynthesis by Chlorobiaceae (green sulfur bacteria) from the Late-Permian into the Early Triassic indicates that hydrogen sulfide did upwell into shallow waters…."

"This hypothesis has the advantage of explaining the mass extinction of plants, which ought otherwise to have thrived in an atmosphere with a high level of carbon dioxide. Fossil spores from the end-Permian further support the theory: many show deformities that could have been caused by ultraviolet radiation, which would have been more intense after hydrogen sulfide emissions weakened the ozone layer."

One cannot prove that anoxic conditions leading to hydrogen sulfide production caused this particular event. However, the data indicates that considerable amounts of hydrogen sulfide can be produced by anoxic oceans. Waking up to oceans that reek of hydrogen sulfide may not kill you, but you might wish you were dead.

In any event, it is time to begin worrying more about what we are doing to our oceans. Gershwin could well be correct. The combined effects of pollution, global warming, and overfishing may have taken us to a state from which we can’t recover.

The Scent of a Man—and a Woman’s Response

Jeffrey Mogil and his co-investigators produced an article that generated comment in several media outlets. The most interesting, perhaps, is that provided in The Economist: Sex, writhes and videotape. This lede was provided:

"Rodents feel less pain when men are around. For scientists, that is worrying"

Scientists have figured out a way to determine how much pain mice are suffering by observing their facial characteristics. When Mogil and his team injected a substance into the legs of mice to induce pain, they observed that the level of pain suffered depended on which of the observers happened to be present. The intention was to verify that the presence of an observer might affect the response of the mice. What they actually found was that the effect of the observer appeared only when males were present. In fact, what the mice were keying on was not the observer himself, but on the smell of the observer. Clothing worn by a male would induce the same effect.

It should be understood that the scent of a man did not produce a soothing effect; rather, the investigators were able to determine that what was actually happening was fear generation, and fear, via a process known as fear-induced hypoalgesia deadened the pain. From Wikipedia:

"Fear induced hypoalgesia is another example of a mechanism controlled by opioids. It is postulated that fear is a defense mechanism that has evolved over time to provide protection. In the case of hypoalgesia, a decreased response to pain would be very beneficial in a situation where an organism’s life was at stake, since feeling pain would be a hindrance rather than a help. It has been well documented that fear does cause a decrease in pain response however much like the exercise induced hypoalgesia, the exact mechanisms of action are not well understood. Studies have shown that opioids are definitely involved in the process, yet opiates alone do not completely explain the analgesic response. What the other mechanisms of action are is still unknown."

Was everyone aware that our body produces various forms of illegal substances in order to get itself through the day?

The article in The Economist summed up the situation in this colorful manner:

"Simply put, the animals were being scared painless. (A significant increase in faecal pellets suggested they were scared shitless as well.)"

And on a more serious note:

"This is an important finding. At the least, it may account for some failures to replicate results in animal experiments, a perennial problem in the field. And, because stress affects numerous bodily responses besides pain, research in many areas may be affected. Dr Mogil suggests, therefore, that the sex of those who conduct experiments needs to be a matter of record, included routinely in the methods sections of research papers."

The possibility that the results of experiments with animals may be compromised by scents produced by humans is certainly important, but should it be so surprising? We, as members of the animal kingdom, have many attributes in common with the other members. We share much of our genetic makeup and produce and use many of the same chemical substances. That natural selection within a species would produce variations in usage and response to chemicals should not be surprising. From her book Mother Nature: Maternal Instincts and How They Shape the Human Species, Sarah Blaffer Hrdy provides this perspective:

"Foragers, primates, mammals—human legacies spiral backward through time, like the coils of DNA that connect us, linking us to long-ago life-forms. Evolutionarily, humans are a ‘mixed bag.’ A line from an old nursery rhyme, "Snips, snails, and puppy-dog tails," isn’t too far off the mark—not just for boys but for everybody. A thrifty matron and inveterate recycler, Mother Nature is slow to discard leftovers. Conservative retention of useful molecules explains why the same endorphins [opioid], the natural morphine that made the pain of my children’s births bearable, are also released in an earthworm when my garden spade accidentally severs it. The innate immune system that protects my body from bacteria makes use of the same kind of proteins that perform this function in fruit flies."
　
What will be most interesting about this article we have discussed are not the precise details, but the indication that human scent can have effects on animals. If a human’s body odor can produce responses in mice, can it produce responses in other humans?

Consider this information from Wikipedia on how body odor affects animal and human activities.

Body odor is largely influenced by major histocompatibility complex (MHC) molecules. These are genetically determined and play an important role in immunity of the organism. The vomeronasal organ contains cells sensitive to MHC molecules in a genotype-specific way. Experiments on animals and volunteers have shown that potential sexual partners tend to be perceived more attractive if their MHC composition is substantially different. Married couples are more different regarding MHC genes than would be expected by chance. This behavior pattern promotes variability of the immune system of individuals in the population, thus making the population more robust against new diseases. Another reason may be to prevent inbreeding.

While we may not be as adept as some animals at consciously detecting smells, it does not mean that we don’t register and process their existence. And matches are not made in heaven, they are made by genetic mismatching—isn’t that fascinating.

"Humans have few olfactory receptor cells compared to dogs and few functional olfactory receptor genes compared to rats. This is in part due a reduction of the size of the snout in order to achieve depth perception as well as other changes related to bipedalism. However, it has been argued that humans may have larger brain areas associated with olfactory perception compared to other species."

Hyrdy follows up on this notion that humans form positive or negative responses to others due to their body odor.

"A curious reminder of how adaptive it once was for a pregnant woman to be near kin when pregnant persists in a modern woman’s sense of smell. As has been experimentally demonstrated for other mammals, ovulating women prefer the scent of males who have genetically produced immunological attributes….different from their own. Presumably this is to decrease the chances that a woman will mate with close kin. Mice manage to avoid incestuous matings this way, by sniffing the male’s urine. Women use body odors instead. They can distinguish between man’s smelly T-shirts, and rank them as either ‘attractive’ or unattractive.’ Instead of preferring alien smells, very different from their own, however, women taking birth control pills that simulate pregnancy exhibit the reverse preference: they prefer the smell of those with immune systems genetically most similar to their own….Perhaps women whose bodies have been artificially induced to simulate pregnancy subconsciously gravitate toward kin."

If so, it would be interesting to ponder what might be the effects of birth control pills on natural selection among humans.

When Mogil’s team performed their experiments on mice they substituted aromas from androstenone and androstadienone, compounds found in male sweat and urine, and observed the same result as with actual males. Yes, just as do their mice brethren, men leave their markers in their urine.

Wikipedia provides this information about androstenone:

"Androstenone….is a steroid found in both male and female sweat and urine. It is also found in boar's saliva, and in celery cytoplasm. Androstenone was the first mammalian pheromone to be identified. It is found in high concentrations in the saliva of male pigs, and, when sniffed by a female pig that is in heat, results in the female assuming the mating stance. Androstenone is the active ingredient in 'Boarmate', a commercial product made by DuPont sold to pig farmers to test sows for timing of artificial insemination."
　
It seems likely that some will be amused by the association of the scent of men with that of pigs.

And then there is this:

"To animals, the smell of androstenone can act as a social sign of dominance, or it can be a way of attracting a mate. This smell, to some animals, has a huge impact on behavioral patterns in the specimen."

Different scents mean different things to different species. Perhaps Mogil and company didn’t so much discover anything very new, but they did package their results well.

And this about androstadienone:

"Androstadienone….is a chemical compound that has been described as having strong pheromone-like activities in humans. It is a metabolite of the sex hormone testosterone: however, androstadienone does not exhibit any known androgenic or anabolic effects. Though it has been reported to significantly affect the mood of heterosexual women and homosexual men, it does not alter behavior overtly, although it may have more subtle effects on attention. Androstadienone is commonly sold in male fragrances, it is purported, to increase sexual attraction."

So, heterosexual women and homosexual men respond similarly to male scent. Can you still believe that homosexuality is a lifestyle choice?

We often find it amusing to observe other animals as they go through their sniffing rituals. Perhaps we do many of the same things—we just do them subconsciously.

The Real World War Z: Jellyfish

We usually become aware of jellyfish when they suddenly appear in large numbers called "blooms." Such blooms are a natural part of the jellyfish lifecycle. What is of concern is the fact that these blooms are becoming more common, more intense, and are causing more problems, a sign that the ocean ecology is changing in a way that is more favorable to jellyfish populations.

Lisa-ann Gershwin has written a book that introduces the reader to the weird and frightening world of jellyfish and their actual and potential effects on the ocean environment: Stung!: On Jellyfish Blooms and the Future of the Ocean. This book should be read by those interested in jellyfish, but, more importantly, it should be read by those interested in the future of our oceans—the actual focus of the work.

Theo Tait wrote a review of Gershwin’s book in the London Review of Books. He provided this summary:

"According to Lisa-Ann Gershwin’s disturbing book, the jellyfish is an ‘angel of death’, a harbinger of ‘planetary doom’ likely to be the ‘last man standing’ in what she describes as our ‘gelatinous future’."

He also provided this assessment of the book:

"Stung! is a serious monograph, a guide to jellyfish biology and to the recent explosion in jellyfish blooms by an expert in the field…. it’s a serious monograph disguised, quite convincingly, as a monster movie. It begins with a series of horrifying vignettes of jellyfish on the rampage, such as the ‘mass fish-kill’ events suffered by salmon farms."

Continuing in the monster-movie vein, he chose to title his review Water-Borne Zombies.

Given that zombies—and vampires—appear so much in popular entertainment, one has to wonder if we are, perhaps, producing a generation that might be confused about the existence of these mythical creatures. Tait’s reference to zombies is intriguing because some of the attributes of jellyfish bear resemblance to what is commonly thought of as "the undead." Thinking of jellyfish as zombies might prove an interesting means of describing their properties. We shall see.

The best dictionary definition of a zombie is probably this one:

"a will-less and speechless human in the West Indies capable only of automatic movement who is held to have died and been supernaturally reanimated"

Being will-less, speechless, and capable of only automatic movement are jellyfish attributes, but it was startling to learn that there is at least one species that has learned to regenerate itself after death—that is more than being undead, that is being immortal.

While individual jellies don’t live forever, it seems the species, as a class, may be immortal. Jellyfish are at least a half billion years old. Prior to the Cambrian Explosion where many new species evolved, jellies seem to have ruled the oceans.

"They have been around at least 565 million years, and probably far longer….Jellyfish are among the world’s most successful organisms, having survived freezes, superheated conditions, shifting and rearranging of continents, mass extinctions, meteor strikes, predators, competitors, and even man."

The greatest, or worst, of the mass extinctions is known as The Great Dying. This occurred about 250 million years ago and is estimated to have rendered about 96% of all marine species extinct. Yet the jellyfish survived.

Gershwin prefers to think of jellyfish as weeds rather than unnatural monsters. One of the things that make a weed a weed is its ability to survive in conditions where other species fail.

"They [jellyfish] share the same weedy qualities that are the essence of weediness in dandelions and cockroaches and their other weedy brethren. They are highly tolerant of a broad range of conditions; they grow fast, breed early and often, and have a large number of young; and they will eat just about anything they can get their lips around."

Now we begin to enter the monster movie realm as Gershwin tells us some of the characteristics of jellyfish.

"Jellyfish sex is like something straight out of science fiction, except there is nothing fictional about it. The methods jellyfish use for reproduction are beyond the realms of Hollywood, and the numbers involved may seem unbelievable. Millions of moon jellyfish aggregate into a massive orgy, same time, same place, everyday. For months. Tens of thousands of eggs is not uncommon….per jellyfish. Per day. Every day. For months. Hermaphroditism. Cloning. External fertilization. Self fertilization. Courtship and copulation. Fission. Fusion. Cannibalism. You name it, jellyfish do it while they’re ‘doing it’."

Jellyfish do not spawn another jellyfish. Their offspring is another adult phase as a polyp that anchors itself to some firm object. This polyp phase can persist indefinitely and it can reproduce by cloning. When the polyp feels the time is right it goes through a process called strobilation.

"Strobilation is where the polyp undergoes a partially metamorphic process, whereby it elongates and differentiates into a stack of disks, like a stack of tiny dinner plates or a role of tiny coins, through a process of transverse fission. These disks develop into tiny, daisy-shaped larval medusae, then begin pulsating and eventually break away to become free swimming."

The number of jellyfish offspring produced in a strobilation event depends on the particular species and on the quality of conditions. Some polyps give off a single larval medusa, others give off as many as 50. This "alternation of generations" provides a powerful degree of freedom in adjusting to changing conditions. The polyp phase can simply set and continue reproducing itself until conditions improve for its potential offspring.

Gershwin provides the example of one jellyfish species that has been observed to have a zombie-like path to immortality.

"….consider the demure but fascinating Turritopsis dohrnii. When the medusa dies, the cells begin to dissociate like any normal organism—that is, it disintegrates. But then something remarkable happens. As the medusa body decomposes, the cells reaggregate and transform into new hydroid [polyp] colonies….The whole transformation from medusa to polyp takes place within a mere five days or so of the medusa’s death. This would be roughly equivalent of a dead butterfly’s cells reforming, all on their own, into a full-grown, fully-formed caterpillar. This is the first known example of true biological immortality."

The feeding habits of jellyfish are also monstrous. When food is scarce they seem quite content to eat each other. And if food is really scarce, many forms of jellyfish are able to effectively eat themselves.

"If food supply gets really scarce, many jellyfish have a backup plan. In times of famine, jellyfish can go without food for a very long time, switching into a process called ‘degrowth.’ Starving jellyfish consume their own body mass very slowly, becoming smaller and smaller, until food is once again available. When they start eating again, they rapidly recover to their normal size—with no ill effects. Throughout the degrowth period, they remain reproductively active and look and act like normal jellyfish, despite becoming progressively smaller."

Any true monster must be capable of frightening those it comes into contact with. Jellyfish are quite capable of that. Jellies are of two varieties; one stings its prey with special cells loaded into tentacles, and the other entangles prey in merely slimy tentacles. The most common form stings. Wikipedia provides this note:

"Jellyfish sting their prey using nematocysts, also called cnidocysts, stinging structures located in specialized cells called cnidocytes….When a nematocyst is triggered by contact by predator or prey, pressure builds up rapidly inside it up to 2,000 pounds per square inch (14,000　kPa) until it bursts. A lance inside the nematocyst pierces the victim's skin, and poison flows through into the victim."

Luckily, not all stings cause serious effects in humans, but some species can cause extreme illness and even death. The truly monstrous part is that these stinging cells seem to have a life of their own, maintaining their threat even after the host specimen has died. Again, from Wikipedia:

"In 2010, at a New Hampshire beach, pieces of a single dead lion's mane jellyfish stung between 125 and 150 people."

Gershwin provides some examples of the nastiest specimens.

The box jellyfish, native to the waters around Australia, are referred to as "the world’s deadliest animals."

"They can kill a healthy adult in as little as 2 minutes—the average time to death is 4 minutes….Death is merely a consequence of ‘enough’ jellyfish tentacle coming into contact with unprotected skin—for an adult this is about 3-5 meters (9-15 feet), for a child it is 1-2 meters (3-6 feet)—not much, considering that a mature jellyfish has 120-180 meters (350-550 feet) of combined tentacle length in its arsenal."

And then there is the nasty little jellyfish known as Irukandji, an Aboriginal word.

"Its sting causes Irukandji syndrome, a constellation of seemingly unrelated symptoms. The sting itself is often not even felt, or is so minor that it is dismissed. After a characteristic delay of about 20-30 minutes, the lower back begins to ache, then rapidly escalates to fully debilitating, cramping, or pounding pain. Patients often describe it as akin to being hit in the kidneys with a wooden bat again and again and again, or feeling as if an electric drill is drilling into the back. Then nausea begins along with relentless vomiting—every 1-2 minutes for up to 12 hours. The syndrome rapidly develops into full-body cramps comparable to the bends with shooting spasms in the arms and legs and behind the eyes; difficulty breathing; profuse, drenching sweating; coughing; and muscular restlessness. Many patients feel a creepy skin sensation, often described as feeling like spiders crawling on or worms burrowing into the skin. Many patients feel an ‘impending doom,’ believing they are going to die. Some go as far as to beg their doctor to put them out of their misery."

One of the "benefits" of globalization is that we have enormous ships that suck water up into ballast tanks in one port and deposit it into the waters of another port across the ocean, thus contaminating one ecosystem with specimens from another. The Irukandji was thought to be limited to the area around Australia.

"….we now know of some remarkably distant cases that have occurred in Florida; Hawaii; Thailand; Goa; India; Perth; Western Australia; Cape Town, South Africa; and even North Wales in the UK….In fact, it seems that Irukandjis (as a group of species producing similar syndromes) are distributed from about 55 degrees N to 38 degrees S latitude, that is, most of the recreationally usable oceans and seas of the world."

Jellyfish blooms can create densities of specimens where they are literally cheek to jowl. This density of matter has caused enormous difficulties just by getting in the way. Jellyfish are notorious for clogging cooling vents on everything from aircraft carriers to nuclear reactors. In true zombie-like fashion, they cannot be stopped.

"Chemical repellants don’t work, because jellyfish drift on the current and can’t respond. Electric shocks don’t work for the same reason. Acoustic shocks don’t work, because jellyfish, not having a brain, aren’t afraid of noise. Bubble curtains don’t work because the bubbles kill them and, alive or dead, they block the flow of water all the same. Biocides don’t work for the same reason."

There are occasions where jellies clogging nets are more than a nuisance. Jellyfish can make short work of fish farms if allowed to make contact. Gershwin described one salmon kill that occurred in New Zealand in 1998 when 56,000 3-kilogram salmon were killed within 30 minutes.

"The salmon all swim in one direction inside the circular pens, creating a fairly strong vortex that sucks water from the surrounding area. The Aurelia, being passive drifters, became entrained in the vortex. Too large to pass through the mesh, the jellyfish were pinned against the netting. As the jellyfish struggled against the current and the netting, their mucus, which is profuse and packed with stinging cells, was sucked into the cages. It appears that as the salmon inhaled the mucus, it blocked the oxygen-exchange surfaces of their gills, causing them to suffocate. The stinging cells exacerbated the problem by alarming the salmon, causing them to breathe faster, thereby serving to suffocate them faster."

Not only do they sting with their tentacles, but they emit slime filled with stinging cells that can be sent out, kind of like a calling card announcing "Watch out, I have been here and I will be back."

In the last chapter of her book Gershwin summarizes all the damage we have done to our oceans by pollution and overfishing and reminds us that degrading ocean ecology almost always leads to more favorable conditions for jellyfish blooms. She chose to call that chapter "The Rise of Slime."

Perhaps one day an enterprising author will produce the screenplay for World War S (or World War J).

Inequality, Redistribution, and Economic Growth

Thomas Piketty is the author of a wildly popular book on economics—yes, economics! In Capital in the Twenty-First Century he summarizes years of research into economic history. Based on data extending back to the French Revolution, he was able to conclude that capital (wealth) tends to grow faster than the economy as a whole, thus leading to increasing inequality. The only period in which growth was significantly higher than the mean was in the period after World War II when so much capital that had been destroyed by two world wars and a worldwide depression had to be rebuilt. It is this era of abnormality that most economists have viewed as the norm. Piketty sums up the history of economic growth:

"The key point is that there is no historical example of a country at the world technological frontier whose growth in per capita output exceeded 1.5 percent over a lengthy period of time. If we look at the last few decades, we find even lower growth rates in the wealthiest countries: between 1990 and 2012, per capita output grew at a rate of 1.6 percent in Western Europe, 1.4 percent in North America, and 0.7 percent in Japan. It is important to bear this reality in mind as I proceed because many people think that growth ought to be at least 3 or 4 percent per year. As noted, both history and logic show this to be illusory."

Inequality grew and produced fantastic accumulations of wealth leading up to World War I. After World War II, inequality fell and growth was high. Now we seem to be reverting to the norm as growth slows down again and inequality is seen to be increasing back to pre-World-War-I levels.

The obvious conclusion is that inequality will grow until some catastrophe occurs or some policy intervention is accomplished. This notion is disconcerting to conservative economists because it is inconsistent with their political beliefs. Consequently they feel they must discredit Piketty, not on the basis of his analysis, which appears unassailable, but on the basis of his politics— he writes favorably about the need for redistributive policies.

An article appeared in The Economist that addressed the conservative complaints: Piketty fever: Bigger than Marx. The assault begins by accusing Piketty of "immodesty."

"The book has attracted much criticism, however. The most common complaints fall into four broad categories. The first concerns Mr Piketty’s tone, beginning with the title. A deliberate allusion to Karl Marx’s magnum opus, it suggests both immodesty and an innate antipathy to markets. Some critics object to Mr Piketty’s use of words like 'appropriation' to describe the rising share of income going to the rich. Writing in the Wall Street Journal, Daniel Shuchman, a fund manager, fumed at the book’s ‘medieval hostility to the notion that financial capital earns a return’."

Much of the criticism is aimed at attacking the conclusion that two centuries of history are relevant to our future. Current wealth is not the same as past wealth, is one such claim. People who are wealthy today will not be smart enough to protect their wealth and propagate it into the future is another theme.

One of the claims against Piketty and the need for redistribution of wealth is that redistribution will somehow inhibit economic growth.

"Mr Piketty glosses over the question of whether attempts to redistribute wealth will weaken growth."

There is a new study issued by the IMF—hardly a bastion of liberal thinking—that attempts to put those concerns to rest: Redistribution, Inequality, and Growth by Jonathan D. Ostry, Andrew Berg, and Charalambos G. Tsangarides. They have been studying the effects of inequality on growth and concluded from earlier work that inequality was harmful to economic growth.

"In earlier work, we documented a multi-decade cross-country relationship between inequality and the fragility of economic growth. Our work built on the tentative consensus in the literature that inequality can undermine progress in health and education, cause investment-reducing political and economic instability, and undercut the social consensus required to adjust in the face of shocks, and thus that it tends to reduce the pace and durability of growth."

All developed countries redistribute wealth to a certain extent. An article in The Economist provided this fascinating chart:

This compares the standard measure of inequality of income, the Gini coefficient, as calculated using as-earned income (market inequality) and income after taxes and redistribution (net inequality). Most of the countries listed have similar market inequalities, but differ in the net inequality due to differing redistribution policies.

The IMF study wishes to determine if those more highly redistributive policies act as a hindrance to economic growth. Examination of historical data led to these conclusions:

"First, more unequal societies tend to redistribute more. It is thus important in understanding the growth-inequality relationship to distinguish between market and net inequality."

"Second, lower net inequality is robustly correlated with faster and more durable growth, for a given level of redistribution. These results are highly supportive of our earlier work."
"And third, redistribution appears generally benign in terms of its impact on growth; only in extreme cases is there some evidence that it may have direct negative effects on growth. Thus the combined direct and indirect effects of redistribution—including the growth effects of the resulting lower inequality—are on average pro-growth."

The emphasis is that of the authors of the report.

And so another economic assumption cherished by politically conservative economists bites the dust.

Shifting Baselines: Oceans, Economics, and Education

Lisa-ann Gershwin has produced a fascinating book describing the decline of our oceans due to mankind’s abuse: Stung!: On Jellyfish Blooms and the Future of the Ocean. She places the disaster unfolding in our aquatic environment on a par with the climate change being caused by the spewing of green house gases into the atmosphere. However, while people still believe the atmospheric effects can be reversed or stabilized, Gershwin believes the damage to the ocean ecologies has been too great and may not be reversible. She arrives at this conclusion:

"….we are creating a world more like the late Precambrian than the late 1800s—a world where jellyfish ruled the seas and organisms with shells didn’t exist. We are creating a world where we humans may soon be unable to survive, or want to."

Gershwin’s book details why that rather startling conclusion has credibility. It tells a frightening tale that deserves greater discussion—one that will receive further attention in the future.

Gershwin, in describing the failure of our ocean ecologies identifies an interesting concept referred to as "shifting baseline theory." The notion refers to the problem of identifying what is natural or normal when we begin to observe a situation only after it has already been altered form its natural state. For ocean life the normal or natural state existed before humans began industrial-scale harvesting of sea life (around the late 1800s). The true baseline is unobservable so we define what we now see to be the normal to strive to maintain.

This notion was popularized by Daniel Pauly who observed that baselines would tend to shift as each new generation of scientists enters the arena and gradually redefines "normal" to be consistent with their current observations. The net result of which would be (from Pauly):

"The result is a gradual shift of the baseline, a gradual accommodation of the creeping disappearance of resource species, and inappropriate reference points for evaluating economic losses resulting from overfishing, or for identifying targets for rehabilitation measures."

The idea of shifting baselines seems an interesting way to examine other professions for possible errors of perception. A little thought leads to several interesting arenas where basic tenets may be far from "basic." Here are two examples.

There is an almost direct analogy between oceanography and economics with regard to baseline shift.

Thomas Piketty, in his book Capital in the Twenty-First Century, performs a trick of which Gershwin and her colleagues are incapable. He and his colleagues have cleverly extracted and analyzed economic data that extends back for a few hundred years. His long perspective reveals to us that the last few generations, when our expectations and our economic beliefs congealed into dogma, were an aberration that was caused by two world wars and a worldwide depression. The era of high economic growth rates after World War II, which has become our ‘normal," was a result of the need to rapidly rebuild the capital destroyed beginning with World War I. With the exception of that exceptional period, high growth is not consistent with historical data.

"The key point is that there is no historical example of a country at the world technological frontier whose growth in per capita output exceeded 1.5 percent over a lengthy period of time. If we look at the last few decades, we find even lower growth rates in the wealthiest countries: between 1990 and 2012, per capita output grew at a rate of 1.6 percent in Western Europe, 1.4 percent in North America, and 0.7 percent in Japan. It is important to bear this reality in mind as I proceed because many people think that growth ought to be at least 3 or 4 percent per year. As noted, both history and logic show this to be illusory."

In other words, Piketty has demonstrated that our economic baseline has shifted to be consistent with an anomalous period in history, rather than to periods of normalcy. While underdeveloped countries can maintain high growth rates for periods of time, the already developed countries cannot expect to do the same.

The field of education also provides areas in which shifting baselines seem to be prominent. Josh Boldt provides us with this perspective on what he describes as Higher Education’s Shifting Baseline Syndrome.

"In 1980, only about 32 percent of faculty members were teaching off the tenure track. By 1993, that number had grown to 58 percent. Just 14 years later, in 2007, approximately 70 percent of professors held contingent positions."

"As these numbers (all collected by the American Association of University Professors) reveal, the ratio of tenure-track professors to non-tenure-track faculty completely flipped during that 27 year period. At the same time, the percentage of contingent faculty positions more than doubled."

"Twenty-seven years is less than the length of an academic career. That means much of the existing professoriate has watched its profession crumble away. Have you turned your head as a tenure line was replaced with a contingent position that doesn’t provide a living wage? Have you closed your eyes and held your nose while the carcass of the university faculty has decomposed outside your office?"

In other words, the old baseline indicated that if you paid an enormous amount of money for a college education there was a good chance that you would encounter teachers who were serious scholars in the subjects they taught. The new normal suggests that if you pay an enormous amount of money for a college education, you are most likely to encounter teachers whose claim to fame consists of the willingness to teach for near the minimum wage.

Colleges and universities seem to have concluded, in this shifted baseline, that teaching is not an arena where investment is profitable.

It has become popular to examine old tests given to eighth grade students to gain insight into how our current system compares in rigor with what students had to learn in generations past. Martin Peretz provides an example in a piece in the New Republic: An 1895 8th Grade Final Exam: I Couldn't Pass It. Could You?

"Remember when grandparents and great-grandparents stated that they only had an 8th grade education? Well, check this out. Could any of us have passed the 8th grade in 1895?"

"This is the eighth-grade final exam from 1895 in　Salina , Kansas , USA　.. It was taken from the original document on file at the Smokey Valley Genealogical Society and Library in Salina, and reprinted by the　Salina Journal."

There was a time when eighth grade was expected to be the end of education for most people and it was expected that at that point they would have to be ready to take care of themselves in the cruel world. Now an eighth grader is just at an arbitrary point on a long journey. Could it be that we have gradually come to expect less and less from our children over the years?

The perceptive reader should have little difficulty in identifying other areas in which we have gradually allowed norms to be redefined as a matter of convenience or profit.