New Mysteries of the Human Microbiome: Cancer and Fungi

 

The idea that cancer is caused by a fungus, or that it may even be a form of fungus has been proposed by the Italian physician Tullio Simoncini. His ideas have been thoroughly demonized and Simoncini himself has seen his license of practicing medicine revoked. 

Now, don't make me intervene in a matter of which I know very little and, for sure, I am not saying that Simoncini is right. I am just noting that, after what we saw happening with the COVID19 story, the demonization of everything which is not "official" in medicine should be taken with a lot of caution.

The thing which I think matters is how complicated things are in everything that has to do with human health. Cancer is normally described as a mutation that makes cells lose their discipline and start reproducing wildly. Things are not so simple as that, I think. The human body has defenses that can rapidly get rid of any rogue cell and it is strange that these defenses become ineffective when dealing with tumors. And, indeed, the story of cancer growth is much more complicated than that. 

Simoncini may have had an interesting intuition when he proposed an important role of fungi in human cancers. You can read the story in this recent paper

https://www.cell.com/cell/pdf/S0092-8674(22)01127-8.pdf

which is structured as a headache machine from the first ten lines of text. Nevertheless, I think the point it makes is clear: all the cancer types the authors studied had some fungi associated with them. That is a new piece of information that goes in parallel with the fact that cancers also harbor special bacteria. What is the role of this microbiome? Nobody knows and, correctly, the authors state that "they have not established causation," even though it seems that the presence of fungi is, sometimes, associated with more aggressive cancers.  

I think it is possible to say that cancers are holobiont-like assemblies of cells, bacteria, and fungi. If they are, that could explain their resilience and their stubbornness. Holobionts are machines that optimize their own survival, and, in this case, it is unfortunate that the cancer holobiont doesn't seem to care about the survival of its host. Maybe, in the future, we'll learn more about this subject and perhaps we'll find a way to exploit this knowledge to help people who are struck by cancer. For the time being, we can be awed, as usual, at the incredible complexity of life in all its forms. 

More discussions on cancer and fungi at

https://www.algora.com/Algora_blog/2022/10/02/7787

https://www.nature.com/articles/d41586-022-03074-z

https://www.healthline.com/health/is-cancer-a-fungus

The Brain, the Gut, and How we get Old

A message sent to the "Proud Holobionts" forum. If you are interested in joining it, write at prudentlobster(thingette)gmail.com. Image from the Leverhulme Center for the Holobiont (yes, there exists such a thing!!)

Dear colleagues,

while every day humans demonstrate more and more their stupidity in the way they deal with each other, there is still such a thing as "real" science that moves onward. I found a recent paper by Dilara Hasavci and Thomas Blank of the University of Freiburg, Germany, that I think may be of interest to you at:

https://www.frontiersin.org/articles/10.3389/fncel.2022.944526/full

I do not claim to have been able to able to read and digest the whole paper, but it is surely fascinating. It is about how the health of the human brain is correlated to the gut microbiota. It sounds strange: why should these two organs be so strictly related to each other? And, yet, the brain is far from being a squishy version of the central processing unit of a computer. It is continuously kept, managed, maintained, repaired, and upgraded by a hugely complex system of specialized cells, mainly the "microglia," but also a host of macrophages: the authors say:

"Parenchymal microglia and perivascular, meningeal, and choroid plexus macrophages, representing non-parenchymal CNS-associated macrophages (CAMs), are among the innate immune cells of the brain (Kierdorf et al., 2019). Together, they significantly influence cerebral inflammation and can be targeted by gut-derived metabolites, especially with increasing age (Mossad and Blank, 2021). Activities connected with macrophages' highly developed lysosomal compartment are among their main tasks. Microglia and macrophages express a number of receptor families that help them degrade old, necrotic tissues and harmful substances from the circulation and their surrounding milieu (Prinz et al., 2017). The CNS is usually only mildly affected by transient activation of brain macrophages. Aging, on the other hand, is associated with chronic systemic inflammation and persistent brain macrophage activation, which can cause major physiological, behavioral and cognitive dysfunctions"

Surprisingly, or perhaps not, this apparatus is deeply affected by the gut microbiome. The connection is through the blood circulation system:

"Studies in germ-free (GF) mice revealed the importance of the microbiome in microglial development and maturation, as well as function in the adult brain. Microglia from adult GF and specific pathogen-free (SPF) mice display different morphologies including branch points, dendrite length, segment number, and cell volume. Additionally, the transcriptomic profile of microglia in GF mice shows a downregulation of several genes involved in cell activation and induction of immune response (Erny et al., 2015). The lack of mature gene expression in these microglia is linked to the absence of microbiota in the gut intestinal tract and disrupts their ability to respond to immunostimulants"

and

"Countless bacteria, viruses, yeasts, bacteriophages, and fungi inhabit our bodies. While microorganisms can be found on almost all environmentally exposed surfaces of our body, the gastrointestinal tract (GIT) shows the highest number and density of microbiota. These communities have significant impact on numerous physiological mechanisms, such as function of the immune system and metabolism (Zhuang et al., 2018; Dabke et al., 2019). The gut modulates several functions in the brain by bacteria-derived metabolites, hormones, and neuroactive substances reaching the CNS via the vagus nerve, enteric nervous- and circulatory system, and immune system"

And finally, note that

"Several studies have found that microbial metabolites can affect gut–brain responses, affecting the morphology and function of brain macrophages. These changes include their polarization and phagocytic capacity, which, in turn, controls behavior and emotional processes."

In short, the way we get old strongly depends on our gut microbiota. It seems also probable (although they do not say it in this paper) that the fact that some of us lose our brain capabilities with age also depends on that. I was just discussing today with a distressed colleague whose mother (88 years old) is going down the dementia road -- and yet, my wife's mother reached 101 years old without losing her mind. Is it all due to the gut microbiota? It would be wonderful if we could cure dementia with gut bacteria but, as they say in the paper,

" A roadblock in today's microbiota-based biomedical research is the modest and long-term impact on psychological and cognitive performance. Probiotic and microbiota-based therapies may take months to years to affect neuropsychiatric illnesses"

So, there are many things we still don't know about this story. It is another facet of the complexity of holobionts.



U.B.

The Krebs Cycle: The Origin of Life?

 

You probably know Nick Lane for his books, such as the rather famous (among some slightly nerdy people, I read it twice!!) "The Vital Question." An older, but still interesting, book by Lane is "Oxygen, the Molecule that made the World."

Nick Lane was recently interviewed on "Nautilus" about his new book, "Transformer: the Deep Chemistry of Life." It is about the Krebs cycle, the engine that powers all the holobionts on this planet. Here, Lane describes how we may be finally cracking the mystery of the origins of life: an epochal discovery. You probably remember how, in the 1950s, it was discovered that the so-called "primordial soup" could generate aminoacids when exposed to ultraviolet rays or electrical discharges. Then, it became fashionable to think that life could have developed on Earth as the result of the assembling of aminoacids to form DNA or RNA molecules. It also became fashionable to think in terms of the "RNA world" that may have preceded the current molecular structure of cells.

Alas, it didn't work. Aminoacids stubbornly refused to assemble themselves into anything more than short-chain peptides, molecules akin to proteins, but much simpler and smaller. This field was gradually abandoned for lack of success in obtaining any useful results about the origin of life. . But now, Lane is reconsidering the idea with a new take: trying to see if it is possible to self-assemble the Krebs cycle or at least something that resembles the Krebs cycle. (Image from Wikipedia)

Fascinating story. I am going to order Lane's new book, even though I don't guarantee that I am nerdy enough to read it twice (maybe not even once), but I'll try.

And, as usual, onward, fellow holobionts!!

The Role of the Forest Holobiont in Earth's Climate: More Important than it was Believed so far

Above, the talk by Anastassia Makarieva at the International Conference on Basic Science for Sustainability in Belgrade, on Sep 22, 2022

It is about an innovative and important interpretation of the current climate situation. Anastassia is proposing that the warming of the atmosphere may be caused not just by the accumulated CO2, but by a radiative forcing of the same order of magnitude generated by deforestation. Earth's forests are giant holobionts coupled and embedded in the even larger holobiont that's the whole ecosystem. It is not surprising that they strongly affect climate, and not just by the conventional factors, albedo and carbon sequestration. There is much more than that, as you can learn by watching the clip, above.  

I don't have to tell you the consequences of this concept. If it turns out to be true (and I think it might well be), it means that we have done a lot of wrong things in trying to mitigate global warming, for instance proposing "biofuels" obtained from wood. But there is much more: it is a complete revolution in the way we see Earth's climate system. Forests not only cool the atmosphere, but also stabilize the climate. This means not only that we need more forests, but that some ideas such as carbon sequestration and geoengineering could do a lot of damage if not coupled with reforestation.

On the other hand, Anastassia's ideas could also be misunderstood as meaning that Climate Science, as it has been proposed so far, is all wrong. And that's sure to happen if her ideas come into the hands of politically minded people who would use that to propose that there is no such thing as global warming, climate emergency, etcetera.  But if we believe in Science (true science, not TV science) we must not be afraid of the truth.

Onward, fellow holobionts!

The Best Description of Holobionts Ever Written

 

From Prigogine's "The End of Certainty" (1996), citing Bierbacher, Nicolis, and Shuster:

The maintenance of organization in nature is not -- and cannot be -- achieved by central management. Order can only be maintained by self-organization. Self-organizing systems allow adaptation to the prevailing environment, i.e. they react to changes in the the environment with a thermodynamic response which makes the system extraordinarily flexible and robust against perturbations from outside conditions. We want to point out the superiority of self-organizing systems over conventional human technology which carefully avoids complexity and hierarchically manages nearly all technical processes.

What is Science? Figuring out God's Will

Here is an interesting post by Ian Schindler,  It is not directly related to holobionts, but it deals with the way we see the world. Knowledge is something that needs to flow freely among people, just as information flows freely among the nodes of all good holobionts. Ian Schindler teaches at the Capitole University in Toulouse (Fr) and is also a member of the "proud holobionts" discussion group. If you wish to join the group, write me at ugo.bardi(swinglette)unifi.it.

A post by  IAN SCHINDLER:

What is science? To me science is trying to figure out God's will playing by the brutal rules of science which are:

1. God's will is explained using laws.
2. The laws must be precise and significant.
3. If your theory does not agree with empirical evidence, it's wrong.

An immediate corollary of rule 3 is that it is impossible to prove a scientific theory is correct. It is only possible to prove that it is wrong. It is wrong if it doesn't agree with observation. The scientific theories we accept are those that have not yet been proven wrong.

Richard Feynman (who was perhaps not such a fine man but he was a fine physicist and entertaining) on this topic: https://www.dailymotion.com/video/xp20d8

Remark: The law of supply and demand violates what Feynman calls vagueness and I call significance. It cannot be proved wrong being compatible with all possible price data. Thus nothing can be deduced from it. One can substitute "The price is the will of God" for the law of supply and demand.

Throughout history, good scientists have been spectacularly wrong about many things. In some sense, the smarter they are, the better they can be at fooling themselves. Max Planck (who chose to publish Einstein's papers on relativity) said something quite illuminating: "A scientific truth does not triumph by convincing its opponents and making them see the light, but rather because its opponents eventually die and a new generation grows up that is familiar with it."

Example: When I was young I was told that the Catholic Church put Galileo in prison for supporting the heliocentric theory of the universe. What my teachers failed to add was that the Church jailed Galileo at the bidding of scientists working on the geocentric theory of the universe. Scientists who had worked very hard on the geocentric theory were understandably more upset by the heliocentric theory than theologians. See https://www.catholic.com/tract/the-galileo-controversy

That is why I pick my fights. I teach mathematics to economists. I do not hide from my economist colleagues that I am very dubious as to the usefulness of their theories. But I waste no time trying to convince them that my theories are more useful. I do try to isolate them. I explain my economic theories to students and non economists. Note that there is a trend that winners of the prize in economics in honor of Alfred Nobel is going increasingly to economists doing empirical work. This is due to the failure of mainstream economic theory to predict events. 

Similarly, I do not waste time trying to convince global warming skeptics that global warming is occurring. I do use probability. I ask them what they think the probability of global warming is. I also nail them for vagueness. If someone talks about "natural temperature variation", I immediately substitute "the will of God". Moreover, I tell them that I will believe that global warming is not occurring through increased greenhouse gas emissions when they provide a mathematical model that explains the earth's change in temperature over time independently from the composition of the atmosphere.

Mathematics is the language of science because of the precision of mathematical statements. A revolution occurred in science (and mathematics) when Newton wrote down a differential equation to describe gravitational attraction.

Of much concern to me is the amount of censorship occurring just about everywhere and the false news disseminated by mainstream media. Because it is so easy to document falsehoods perpetrated by mainstream news media, it is difficult to know who to trust. This makes it easier to get suckered into a
conspiracy theory rabbit hole. Note that Mark Zuckerberg recently stated that the FBI influenced Facebook to censor the (true) Hunter Biden laptop story before the 2020 election. This is a major reason that I support substack. I think it is much healthier to have a place where controversial ideas, scientific or otherwise, can be openly debated. Glenn Greenwald who worked for The Guardian when he helped break the Snowden story, helped found The Intercept because of editorial pressure at The Guardian. He resigned from The Intercept because of editorial pressure there and now publishes out of substack. He has documented how mainstream media disseminates false news stories, see for example

https://greenwald.substack.com/p/how-do-big-media-outlets-so-often,
https://greenwald.substack.com/p/corporate-news-outlets-again-confirm,
https://greenwald.substack.com/p/corporate-medias-double-standard

Matt Orfalea makes videos documenting fake news disseminated by mainstream media: https://rumble.com/search/video?q=orfalea It is a bit shocking to see with what fervor the media can insist a falsehood is true.

Note that I linked Orfalea's rumble channel rather than his youtube channel. I support rumble for the same reason I support substack, no censorship.

I will add that the censorship extends to peer-reviewed scientific papers. Many papers are rejected not for any scientific reason but because either the result is contrary to an accepted result, the references are not those of the referee, or the author is unknown. One only has to look at the difficulties Lynn Margulis encountered in her career.

Reality is real no more. Whom to trust in science?

 

The "World Climate Declaration" returns. It is a document that has been around in various forms since 2009 that has all the appearance of "legitimate" science. It is not, but how to judge? We face an unsolvable epistemological problem.

Recently, one of the members of the Holobiont Group posted the link to a document titled "There is No Climate Emergency" on FB. He defined it as "bonkers" -- it was clearly irony. Yet, Facebook's Fact-Checkers don't know irony, and the post was promptly censored and branded "false information."

That highlights, I think, the problem we have with science. Place yourself in the shoes of a person who has no training in science, and knows only what can be read in the media about climate. What should she think about this story? 

We have a document that, at first sight, it looks legitimate. The signatories are bona fide scientists, although one may notice that some of them are a little old (actually, more than a little) (*). But being over 90 does not mean being automatically wrong. And what to say about the anonymous "fact checker" who so peremptorily deemed the document to be "false"? The link provides leads only to a post in Croatian, written by a young lady named Melita Vrsaljiko (https://www.linkedin.com/in/melita-vrsaljko/). She has a degree in journalism awarded by the Faculty of Political Science in Zagreb. Probably she is the "fact checker" hired by Facebook who struck down the post. If this is the case, one could reasonably be a little vary of a fact check based on something written by the fact-checker alone. 

Machine-translated into English, the "fact check" is not much better than the documents it purports to check. Among other things, we are told the document is "false" because it was diffused also by a site that diffuses "anti-vaxxer" information. And also because only a few of the signatories are climatologists. The accusation of the authors not being climatologists is a little perplexing since it comes from someone who has no other qualifications than a degree in journalism. (**)

The problem, here, is that when we deal with climate change, most of us, even scientists competent in our fields, are unable to comprehend the immense complexity of the story. The only way that people can do that is based on the principle of authority. But are 1200 old scientists signing a document titled "There is no Climate Emergency" a sufficient authority? Or you'd rather trust the large number of scientists who adhere to the IPCC (I don't know how many, but surely many). But truth, as we all know, is not based on the majority of believers and from the time when Karl Rove said that "we create our own reality, reality has ceased to be real. So, why should trust FB's fact checkers? Or anyone else?  

This is just not possible. We cannot do science in this way. We need to rethink the whole idea. You may think that I am a little manic (probably I am), but I think we should apply the concept of holobiont to science, too. Maybe we could think of a "horizontal" science, where facts and ideas are shared among peers, that is all of us. That is they do not arrive from the sky, screaming, "trust me, I am Science!!!" They come from our peers, whom we trust. Science cannot come as a revealed trust. It must come from all of us. 

We keep at it. Onward, fellow holobionts!

(*) The Nobel prize at the top of the list is 93. The Italian member of the group (Prof. Zichichi) is 92. About this Italian member, I can tell you that he has made a fool of himself in public so many times that there is an entire popular literature dedicated to his mistakes (for those of you who can read Italian, there is a popular term "Zichicche," not literally translatable, but more or less meaning "Zichichi's gems" -- intended as howlers). On this, though, I can tell you that I have no respect for the people who have made money and a reputation for themselves by selling books that ridicule a scientist who, with all his idiosyncrasies and naivety, has some merits.

(**) I am not criticizing Ms. Vrsaljiko. She did her best, and her article is good in many respects. But the task she was charged with was basically impossible.