The tragedy of science: we cannot fault the tiger for being the tiger

Vinay Prasad is a young researcher in oncology who recently published the post reproduced below on his blog. It is about how oncology has become a field whose main purpose is mainly to enrich companies and practitioners. The tragedy of these reflections is that they apply just as well to many other fields of science. And it is sad to think that science started as a disinterested search for truth, and then it was turned into an ideological shield for criminal activities. Correctly, Vinay Prasad says that we cannot fault corporations for aiming at profits (we cannot fault the tiger for being the tiger). But we can fault the whole health system built with the purpose of making money instead of helping patients. Vinay Prasad's most recent book (2020) is titled "Malignant". I am reading it. It was already rather dark, but not as pessimistic as his latest post. 

Here are some excerpts from Vinay Prasad's text, you can look at the complete text on his blog:

The Tragedy of Oncology

Vinay Prasad

Excerpts from https://vinayprasadmdmph.substack.com/p/the-tragedy-of-oncology

I started my journey into cancer medicine more than 10 years ago, and it has been joyous and tragic, fulfilling and frustrating, all at once and often on the same day. Recently, I returned from our latest conference, and I had a chance to think about that experience a few days later in the mountains of the Sierra Nevadas. My conclusion is grim.

....

The tragedy in oncology is that we have dismantled the system that is meant to tell real innovation from pseudo-innovation. Almost no one understands the problem, even few care about fixing it, and instead most hope to fatten themselves of the riches, while the opportunity exists. Meanwhile, we have entirely lost sight of the goal— the purpose of our task. We have forgotten that this is about helping people sick and dying of cancer live long and live better. That goal is lost.

10 years ago, I believed that, as a younger generation swept through, reform would be inevitable. 10 years later, I see how naive I was. For every young person who understands the problem, there are 9 more salivating at the idea of becoming the next key opinion leader, eagerly going to advisory boards or pharma-sponsored dinners. Every young person who speaks out publicly is advised by colleagues or their boss to stop talking. Some are even told not to (or fearful of) retweeting critical content like mine or Aaron Goodman’s.

.......

Academic leaders. This category contains some massive failures. We have ‘leaders': who are pocketing 10s of thousands from Pharma and defending their (failed) products. What am I to think when the company behind Melflufen hires a leading academic to defend a garbage subgroup analysis at the ODAC? What am I to think when university after university enters into financial arrangements with companies? Pushing back on corporatism is impossible, when you are on the payroll.

Journals and professional societies. Many journals block critical commentary. Many organizations sell out their professional conferences to Pharma. These institutions are now so dependent of Pharma largess that they are powerless to say anything. Only a few voices inside these organizations keep them from toppling into complete advertisements.

Junior faculty. The vast majority are busy running uncontrolled trials that will not help anyone (most uncontrolled trials can’t even answer a useful question). Many have joined ad-boards, etc. Some are studying important topics but have nothing novel to add. An abstract on health disparities that shows… health disparities. Except the solution remains unclear, and the authors think all that is needed are more expensive, mediocre drugs. Cookie cutter projects is another weak spot. If you don’t have a novel idea, it’s ok to think for a while— rather than follow the path of least resistance.

Oncology press. A cottage industry of rag publications cover oncology. They are almost entirely funded by pharma or it’s ads, and they have no critical coverage. Even oncology podcasts are upwardly biased. This is not journalism, but advertisement.

The Industry. The group that I have the least quarrel with is pharma itself. We cannot fault the tiger for being the tiger. Instead, it is the aforementioned entities who have let their guard down. The tiger has a moral obligation to make profit. We were the ones who did not incentivize the right things.

......

How will it end?

Internal reform is not possible. Too many people benefit from the status quo. Reform will come from government regulation— and must come from the USA— that tilts incentives to what matters. I will continue to write, podcast and publish on the flaws of cancer medicine, but going forward, I will spend more time strategizing on political solutions to this problem.

Meanwhile, I won’t forget the goal of oncology: to help people with cancer live as long and as well as possible, using as few drugs as possible, and, pushing for the best evidence to guide those choices. Perhaps we should all have to take that oath.

Mushrooms! Three Minutes of Pure Holobiontic Delight

 

The Return of the Ents: The Tribe of the Trees

Image by VargasNi

The idea of trees moving and fighting humans is old, it goes back to Shakespeare's Macbeth and the prophecy of the witches

Macbeth shall never vanquish'd be until

Great Birnam Wood to high Dunsinane Hill
Shall come against him.

You find the same idea again in Tolkien's "Trilogy of the Ring," with the creatures called "Ents," which attack the city of the orcs at the battle of Isengard. Both Shakespeare and Tolkien express a similar idea, that at some point too much is too much and nature rebels against human evil with all its force. To the point of seeing trees taking their roots out of the ground, and marching against human cities. 

In modern times, the idea that trees and humans are in conflict is gaining attention. The concept of "biotic regulation of the environment" proposed by Makarieva, Gorshkov, and others, is gaining ground in the world. It basically says that if we destroy the world's forests, we destroy ourselves. Not an easy position to take in a world where forests are considered "natural resources" and where the standard economic theories say that a tree has no monetary value unless it is cut down and sold as wood.

Would "humanizing" trees in fiction help people to have a more gentle attitude toward trees? Maybe, but it is not so clear. Personally, I always found depressing Tolkien's walking trees. Their representation in the 2002 movie "The Two Towers" didn't change my opinion of them. They are clumsy, ugly, and not really believable, not even in a fantasy movie. 

Recently, another take on presenting the world from the viewpoint of trees was tried by Stefano Mancuso, well-known botanist at the University of Florence, and an expert in plant neurobiology. If there is a human being on this planet who can know something about how plants think, he is the one! So, he published a novel titled "the tribe of the trees" (la tribù degli alberi). (so far available only in Italian).

I have mixed feelings about this novel. For one thing, it is a well-written story, nice to read, captivating, and with delightful characters.  The story moves onward smoothly, one event after the other, leading to the conclusion when trees discover the problem of global warming -- even though they don't know anything about atmospheric physics and have never seen a human being.  

Mancuso's trees have many "tree-like" characteristics, and they are far from being as clumsy and ugly as Tolkien's Ents. And note that there are no human beings whatsoever in the novel: it is only trees! But Mancuso's trees are, in my opinion, a little too humanized. They can move, speak to each other, and, in many ways, behave like human beings. Mancuso's forest looks very much like a modern university, with its various departments (=tribes) and their researchers, librarians, technicians, etc.

An expert in plant neurobiology, such as Mancuso, could have told us much more about how trees "think," if they do (I think they do!). But I can also understand that in novel terms it is not easy to build a story about creatures whose brain is located underground, cannot move, and perceive the external world mainly as a combination of chemical signals. The power of human imagination is immense, but it would be a truly alien novel, one that maybe only trees could read!

For me, the best human fiction piece that tries to understand trees is "The Secret of the Old Wood" (Il segreto del bosco vecchio) by Dino Buzzati (1935). It is, however, one of those masterpieces that go beyond the mere concept of narrative and touch the very fabric of the universe. If you can understand Italian, read the book or watch the movie (or both). It is a humbling experience that will make you reflect on what it means to be human. Or a tree. 

Flying Rivers, the Biotic pump, and the Consequences of Deforestation

A talk given a few years ago by Anastassia Makarieva where she focuses on the concept of "biotic pump" a fundamental concept of the biotic regulation of the ecosphere, part of the general concept of "Planetary Holobiont." She will update her results in a Webinar to be held on Jan 2nd, 2023. You can register at

https://tum-conf.zoom.us/webinar/register/5016722254879/WN_tDztF8fJSrGWOJLaYv5B2Q

The Holobiont's Decisional System: A Comment by Helga Ingeborg Vierich

Helga in Botswana with two Kua friends (image source)

A post by Helga Ingeborg Vierich


Here, Helga comments on my previous post "Why do we Always Choose the Decisional System that do the Most Damage," where I discuss the case of the sinking of the "El Faro" ship, caused by the way the command structure was organized. "Pyramidal" decisional systems place the power in the hands of a single person, (typically a man) and the person in charge doesn't have the flexibility to change his opinion, nor the capability to access the data on what's really happening. A Holobiont-like decisional system is much more flexible and attuned to the real world, as Helga describes here.  



Dear Ugo; this is wonderful.

It explains the danger of hierarchies of powerful authority so clearly! I am teaching introductory sociology this term and will be making this one of the supplemental readings, for the topic right now is the development of state-level societies. It is, indeed, in state-level societies that we see the development of these kinds of hierarchies.

People have frequently pointed to the pecking order of chickens, and the evidence of hierarchies based on aggression in chimpanzees and baboons, and used this as a justification for human hierarchical social organization. As if it were, thus, "natural". But everything we know now, about the social organization and behaviour of people in "tribal" and "band" level societies (based on hunting, gathering, fishing, swidden horticulture, or nomadic pastoralism) suggests that before the state developed, seniority-based hierarchies of authority rare, and socio-economic and power-based hierarchies were unknown. Decisions were rarely made without extensive discussion.

The whole dynamic of morality in forager economies is to enforce a degree of social equality: the networks are based on relationships of mutual support, not chains of authority. There are no permanent leadership positions. Group actions to enforce punishment of transgressors appear to arrive through consultation and consensus.

We find these forms of consensus-creation preserved in tribal societies as well, even those with more permanent leadership positions. This is perfectly articulated in the following:

“...Roland Chrisjohn, a member of the Iroquois tribe and the author of The Circle Game, points out that for his people, it is deemed valuable to spend whatever time necessary to achieve consensus so as to prevent such resentment. By the standards of Western civilization, this is highly inefficient.

“Achieving consensus could take forever!” exclaimed an attendee of a talk Chrisjohn gave. Chrisjohn responded, “What else is there more important to do?”” (quoted from
http://www.filmsforaction.org/articles/the-more-a-society-coerces-its-people-the- greater-the-chance-of-mental-illness/ )

Unlike the hierarchical systems in many larger primates, like chimpanzees, ranking systems among foragers and even among pastoral and horticultural peoples, are not derived from intimidation and aggression, but by acquired reputation for demonstrated moral virtues - like articulating a consensus. Such people are valued by the community and thus listened to, only after a history of demonstrated integrity involving a list of highly valued signs of good character: generosity, diplomacy, honesty, loyalty and recognized proficiency at important skills (hunting, gathering, cooking, singing, trance-dancing, music, storytelling or comedy).

In other words, they are people of high rank and good reputation. Among hunter-gatherers, therefore, differences in social rank rarely result in social inequality of access to vital goods and services, but instead, ensure such access.

Indeed, aggressive hierarchies are not even innate, even in baboons. Such behaviour is cultural - learned and shared. This was shown very clearly in Richard Sapolsky's story of his Keekorok baboon troop, and how after the alpha males died from tuberculosis, the troop very quickly transformed into a very peaceful troop, and since then, a peaceful approach has become a cultural norm for them. This was in contrast to the normal high levels of stress in the aggressive hierarchies of baboons. Sapolski's research indicates that stress created by hierarchies is a killer in human societies, and he is not alone in saying this. Gabor Mate has been very clear on this too, and has linked stress, addictions, and even the addiction to power.

Yes, our societies, in the world today, need to become more of a holobiont: the integration of many co-dependents is always going to produce a less dangerous and stressful alternative.


regards, Helga

Chip 'n Dale: Holobionts

 

Do you remember Chip 'n Dale? They were created by Walt Disney in 1943. It seemed wholly natural to viewers that they had a nice home inside the trunk of hollow trees. The idea that they were looking for natural cavities appeared from their very first story, which had to do with their attempt to settle inside the barrel of a cannon. 

Cannons are still abundant in the world, but hollow trees don't seem to be so common anymore. Think about that: have you ever seen a hollow tree outside horror fiction or cartoons? I never saw a hollow tree comparable to the fictional ones. It is only in parks that keep old trees that, occasionally, you can still see hollow trees, but rarely with those huge hollows where Chip and Dale could make their home. 

Yet, hollow trees have a special fascination and are part of forest lore everywhere in the world. They are not just fascinating for human beings, they are also home to all sorts of animal species. Birds, typically, but also larger ones, such as raccoons and even bears. In this sense, hollow trees are a feature of the forest holobiont, just one of the many multispecies holobionts that keep the ecosystem alive and adaptable. 

The formation of a hole on a tree stem is a wholly natural process that's generated, normally, by the action of specialized saprophyte fungi -- although woodpeckers can initiate the process and, sometimes, dig quite substantial holes. The plant is not normally harmed by one or a few hollows. Old trees tend to accumulate hollows, and when they die they become "snags," not anymore live trees, but still part of the forest ecosystem, homes to a variety of animal species.  

So, why so few hollow trees around? Have they become an abomination? Apparently, yes, I have a fig tree in my garden with a few hollows in the stem, and everyone who sees it asks when we are going to cut it. And that's the destiny of hollow trees everywhere. If you look at the term on the Web, you'll find plenty of pages describing "hollow tree removal services." It seems that hollow trees are indeed seen as a monstrosity, slated to be eliminated as soon as possible. And whenever a tree develops a hollow, it is plugged with cement or silicon, or whatever. 

More in general, hollow trees are a victim of the "optimization" trend in forest management. It doesn't matter whether it is a plantation or a park, if the idea is to make trees grow as fast as possible, then hollow ones have to be removed. It is typical of human management: it is aimed at maximizing just one of the parameters of the system. Instead, holobionts aim at optimizing all the parameters together. Humans aim at yield, holobionts aim at stability. Maybe, one day, humans will learn, and maybe they are already starting to learn. In the book "Chanterelle Dreams" by Greg Marley, you can find an entire chapter dedicate to how to restore tree hollows for cavity nesters. Some creative methods can be used, such as using shotguns to shoot slugs packed with fungal spawn into the bulk of a tree stem. It seems to be working -- so, not everyone marching into a forest with a shotgun in hand is there to do damage!

Up to not long ago, I was convinced that, apart from my fig tree, hollow trees had been scientifically exterminated in all the areas close to where I live. Instead, I discovered that the avenue just near my home is lined by wonderful honeyberry trees ("bagolari" in Italian), most of which have numerous, well-visible hollows. Some are clearly the result of branches having been cut off, others may have developed by themselves. I won't tell you where exactly this place is, least someone decides to cut these trees for being "dangerous" or to plug the hollows with cement. As far as I can say, these cavities are not inhabited by birds or other animals, probably because they line a trafficked road. But it is nice to know that there are places where owls, squirrels, and maybe Chip and Dale could take refuge if they decided to live in this area. Here are a few pictures. 

How Gaia Saved the Earth from a Cold Death

 

The Goddess Gaia in the form of the winter deity Khione, daughter of Boreas, the North Wind, and the Athenian princess Oreithyia (image by "Nobody-Important"). 

Earth is a fragile planet and it might freeze to a snowball if not taken care of. So far, the Goddess has done a good job at that but, at least a couple of times during the past few billion years, the Earth actually froze. Might that happen again? It seems that we were close to that just a few tens of thousands of years ago. Now, the problem doesn't exist anymore, with humans pumping zillions of tons of greenhouse gases into the atmosphere. And, who knows? Humans could be the tool used by the Goddess to avoid another "snowball Earth." But now we may have too much of a good thing and the Earth risks boiling. Hopefully, Gaia can take care of that, too.   

It is always amazing to realize how complex is the system that we call the "Ecosphere". And how the system's complexity keeps its parameters within the limits needed for life to exist and prosper. It is the concept of "Gaia" as it was proposed by James Lovelock and Lynn Margulis. The ecosystem is in homeostasis and tends to maintain relatively constant parameters by means of a tangle of internal feedbacks, as all complex adaptive systems ("CAS") do. 

But homeostasis doesn't mean perfect stability. The system's parameters may oscillate - even wildly - before the internal feedbacks can bring them back to the "good" values. Sometimes the system gets close to its limits and it may well be that, at times in its long history, the ecosystem risked going over the edge and then Gaia could "die." This seems to be a common destiny for extrasolar planets, as recently argued by Chopra and Linewaver.

A recent paper by Galbraith and Eggleston on Nature starts from these concepts, noting how the concentration of CO2 in the atmosphere never went below ca. 190 ppm during the past 800,000 years. That happened in correspondence with the lowest temperatures ever observed during that period: the planet was going through a harsh ice age.

This figure from a recent paper by Galbraith and Eggleston on Nature shows an interesting fact: the concentration of CO2 in the atmosphere never went below ca. 190 ppm over the past million years or so. Possibly, it touched the danger limit for the ecosystem to survive. For lower concentrations, plants wouldn't have been able to perform photosynthesis and the biosphere would have largely disappeared.

About these ice ages, there is an interesting point related to the system's feedback. The more ice there is, the more reflective the planet's surface becomes (more exactly, the planetary albedo increases). But, the more reflective the planet's surface is, the cooler the planet becomes. So, we have an enhancing feedback that may transform the whole planet into a single, frozen ball: "snowball earth". It has happened, although possibly not completely, at least twice in the history of Earth. It was during the period we call, appropriately "Cryogenian," from 720 to 635 million years ago. It was not a real "snowball" -- not all of Earth was covered in ice. But what was not under the ice was a frozen desert. To give you some idea of the fascination of this subject, here is an excerpt from the abstract of a paper by Hoffmann et al. on "Science"

"....the small thermal inertia of a globally frozensurface reverses the annual mean tropical atmospheric circulation, producing an equatorial desert and net snow and frost accumulation elsewhere. Oceanic ice thickens, forming a sea glacier that flows gravitationally toward the equator, sustained by the hydrologic cycle and by basal freezing and melting. Tropical ice sheets flow faster as CO2rises but lose mass and become sensitive to orbital changes. Equatorial dust accumulation engenders supraglacial oligotrophic meltwater ecosystems, favorable for cyanobacteria and certain eukaryotes. Meltwater flushing through cracks enables organic burial and submarine deposition of airborne volcanic ash. The sub-glacial ocean is turbulent and well mixed, in response to geothermal heating and heat loss through the icecover, increasing with latitude. Terminal carbonate deposits, unique to Cryogenian glaciations, are products of intense weathering and ocean stratification. "

Can you imagine the Earth in these conditions? A wasteland of dry deserts and ice sheets. At that time, there were no multicellular creatures and life may have survived in hot pockets, maybe volcanic lakes, where it was still possible to find liquid water. 

We may have been dangerously close to a new snowball Earth episode during the past million years or so. Not a trifling matter because today the ecosphere is much more complex than it was at the time of the Cryogenian. A new snowball Earth would likely cause all vertebrate lifeforms to go extinct. It is not just a question of being too cold: the limit of concentration of CO2 that permits plants to perform photosynthesis at a reasonable rate is considered to be around 150 ppm, at least for the most common kind of plants. Under that value, all multicellular plants die, and with them all animal life. Only single-celled creatures could eke out a precarious existence in those conditions. 

But something prevented the ice sheets to expand all the way to envelop the whole Earth and, at the same time, prevented the CO2 concentration to go below 190 ppm. What was that? Several hypotheses are possible. Galbraith and Eggleston favor a biological one, saying that:

In terrestrial ecosystems, carbon fixation by plants is limited by low ambient CO2 (ref. 31). On this basis, ref. 12 proposed that CO2-limitation had significantly reduced plant-mediated silicate weathering during low-CO2 intervals of the past 24 million years, thereby enforcing a lower bound on the ocean–atmosphere carbon inventory over >10^5 yr timescales. Subsequent experiments have been consistent with this ‘carbon starvation’ mechanism, showing reduced weathering by tree-root-associated fungi under low CO2 (ref. 32). Although the feedback on silicate weathering would appear too slow to play a role on the 104 yr timescale of glacial CO2 minima 30, it may be possible that strongly reduced weathering rates lowered ocean alkalinity (thereby decreasing CO2 solubility) on a millennial timescale. Alternatively, reduced photosynthesis rates during the LGM (last glacial maximum) would have slowed the accumulation of terrestrial biomass14, consistent with estimates for lower terrestrial primary production rates33. By slowing the accumulation of carbon in vegetation and soils, this would have provided a stabilizing feedback via an increase of the ocean–atmosphere carbon pool.

Complicated stuff, right? But, basically, the idea is that CO2 is slowly drawn down from the atmosphere by a reaction with rocks (silicates), forming carbonates. This reaction is called "weathering" and it is favored by plants, whose roots provide a good environment for it to take place. Fewer plants, less CO2 drawdown. At the same time, a smaller global biomass means that the quantity of CO2 stored in it becomes lower and this extra carbon most likely ends up in the atmosphere as CO2. So, there are two feedbacks embedded in the system that tend to stabilize its temperature. But, as you may understand from the text by Galbraith and Eggleston, it is even more complicated than this! In any case, these stabilizing geobiological feedbacks oppose the ice/albedo feedback and tend to slow down the glaciation before the two sides of the ice sheet touch each other at the equator. 

But suppose that the Earth really became the snowball that some studies claim to have observed: how did it recover? If it is frozen, it is frozen. Maybe not completely dead, but poor Gaia was reduced to a minor sprite inhabiting hot springs. How could Earth return to the lush ecosphere we are used to?

There is an explanation: it is because volcanoes do not care whether the Earth's surface is frozen or not. They continue pumping CO2 and other greenhouse gases into the atmosphere. Again from Hofmann et al. 

“If a global glaciation were to occur, the rate of silicate weathering should fall very nearly to zero (due to the cessation of nor-mal processes of precipitation, erosion, and runoff), and carbon dioxideshould accumulate in the atmosphere at whatever rate it is releasedfrom volcanoes. Even the present rate of release would yield 1 bar ofcarbon dioxide in only 20 million years. The resultant large green houseeffect should melt the ice cover in a geologically short period of time”[(69), p. 9781]. Because Snowball Earth surface temperatures are below the freezing point of water everywhere, due to high planetary albedo,there is no rain to scrub CO2(insoluble in snow) from the atmosphere."

Note one subtle detail: if temperatures were to go below the freezing point of CO2 (-78 C) even in small regions at the poles, that would form a nearly infinite CO2 sink. And that would be "snowball forever" -- maybe it would have made the Goddess Khione happy, but it didn't happen. Possibly, that was too cold even for a Winter Goddess!

In any case, it seems that CO2 was pumped into the atmosphere by volcanoes, maybe it was the work of the volcanic form of Gaia, the goddess Pele, known for her habit of taking lava showers. 

When the CO2 concentration arrived at levels hundreds of times those of the present-day atmosphere, the result was a cataclysmic rapid collapse of the glaciers and a rise in temperatures. Not only the Earth's ecosystem was saved from a cold death, but it rebounded spectacularly: it was now the time of the "metazoa," the formal term indicate animals. There came the Cenozoic, in which we are still living, with its incredible variety of lifeforms when plants and animals colonized the continental lands. 

You see how the job of Gaia is not so simple. it involves a delicate balance of many factors. Some tend to stabilize the system, while others tend to destabilize it. During the past 15 million years or so, cooling factors took the lead and slowly pushed Earth to lower and lower CO2 concentrations and, with that, lower temperatures.

 Image from Wikipedia Commons. The x scale is in million years from the present. Note the rapid cooling of the past million years or so.

We do not know exactly what caused the cooling, there are several theories. But one thing is sure, Gaia started feeling that it was too cold for her, even in her form of Khiome, goddess of ice. She could die and, this time, perhaps for good. 

(Image source)

So, it became imperative for Gaia to mobilize some of the geosphere carbon and push it into the atmosphere in the form of a greenhouse gas that would warm the Earth back to comfortable temperatures. The Goddess Pele was too slow for that, maybe she is now a little tired after blowing CO2 into the atmosphere for four billion years. So, maybe Gaia thought of a more creative solution. 

Why not use those clever monkeys which had just evolved in Earth's savannas to dig carbon out of Earth's crust, combine it with oxygen, and then pump it back into the atmosphere?  It worked: in just a few hundred years, the monkeys managed to bring back the CO2 concentration to the levels that were typical of Earth as it was a few tens of millions of years ago. 

It may be that, now, Gaia faces the opposite problem: those monkeys have pumped so much CO2 into the atmosphere that now we risk pushing the planet on the opposite side of a climate collapse, to a "hothouse Earth" that might kill the biosphere. Something like that happened with the great extinctions at the end of the Permian and the Cretaceous. Alas, life is difficult, but Gaia can cope. Does that mean getting rid of those pesky carbon-burning monkeys? Maybe. After all, Gaia is a Goddess, she ought to know what she is doing and she has no qualms when it is time to do what's to be done. She can find ways. 

(Image Source)