Where did a Nervous System Come From?

Ever wondered how a nervous system evolved, and how we evolved to get around to thinking? If you do think about it, at first sight it is not obvious how it evolved; what caused it? The point about evolution is that it progresses in tiny steps, so what could possibly be a step towards a nervous system? It has to be something really simple that a minor change from the first simple organism that feeds and reproduces, BUT it has to do something that gives it an advantage, so the question comes down to what could that be?

The first thing to note is that there would be little point in a single-cell creature developing such a system. The point of a nervous system is to coordinate the activities of different parts of the whole, but a single cell is sufficiently small that coordination is unnecessary. Notwithstanding that, there may be an advantage for a single cell to sense whether there are nutrients nearby. The first such cells would simply absorb, but if it could sense when there were nutrients or not, it would have a better way of knowing whether to reproduce. That could arise initially with nothing more than having two activities. Microalgae show such an extremely primitive sensing. If a microalga has a good supply of nitrogen, it makes nucleic acid as fast as it  can, together with some protein, and these are just what it needs to reproduce. If it is nitrogen starved, it cannot turn off its photosynthesis mechanism so it takes CO2 from the air and makes lipids. It just swells up with fat! If it cannot get nitrogen nutrients for a prolonged time, it bloats and dies.

According to Musser et al. 2021 (Science 374: 717 – 723) a clue to how the nervous system evolved comes from sponges. Sponges are an animal clade that lack neurons, muscles or a gut, so they are rather simple. They have canals for filter feeding and waste removal and they have cilia that drive water flow. Yet despite this simple structure, they perform whole-body contractions that can expel debris, and while they have no integrated signalling functions, nevertheless they have genetic material usually found in nerves and muscles. Apparently sponges can use an intricate cell communication system to regulate their feeding and potentially eliminate invading bacteria. They do not have neurons, but they have genes that encode proteins to help transmit chemical signals, which could be regarded as an initial move towards a nervous system.

The sponge that was studied has 18 distinct cell types and synaptic genes (i.e. potentially capable of transmitting a signal) were active in some of the cells that were clustered around the digestive chambers.

They then showed that some such cells send out long arms to contact the cells with hair-like protrusions that drive the water flow systems. In other words, there is something there made of protein that starts where food is digested and stretches to the cells that control the flow of water, thus either telling these cells to send more food or alternatively to clear out the debris from previous digestion. It is important to note that these connectors are not nerves and it is not a rapid communication. Nevertheless, a system that could tell when it was time to get rid of debris from the region where it digests would be an evolutionary advantage over those that could not, and would hence take a greater percentage of the food and reproduce faster. Eventually it would predominate, especially those specimens that could do it a little better than the others. Over the generations the system would gradually predominate. It should also be noted that this does not mean we evolved from a sponge. This sort of behaviour could have started many times in different families. The point is, there is a distinct advantage when developing multi-celled creatures for one end to let another end know that it would like more food, or that it is flooded with debris. Obviously, this is a long way from a nervous system. The next evolutionary step would probably be to do it faster in larger multi-celled species. However, the means of sensing food would be the first prerequisite for sending messages to help digestion; it is not just the ability to send messages, but the message must have some sensible relevance. Food (or nutrient acquisition) would be the first reason to communicate across cells. Whether this was really how a nervous system started is debatable, but at least it makes sense.

Scientific Rubbish

Just when I thought that I had probably said enough about bad science, along comes another paper in Nature, ( https://doi.org/10.1038/d41586-021-03035-y) where it was noted that hundreds of junk-science papers have been retracted from reputable journals after fraudsters manipulated the publication process. Many of these were caught in “special issues”, where in some cases the whole issue was rubbish. A special issue is often published when someone suggests that a collection of papers on a specific topic would be helpful. Thus one of those attacked was Springer-Nature’s Journal of Nanoparticle Research. A groups of what appeared to be eminent computer scientists and engineers from well-known institutions in Germany and the UK wrote to the journal’s editors suggesting a special issue about the role of nanotechnology in health care. The editorial board agreed with the proposal and created a special issue entry in its editorial management system and apparently authorised access to three group members so they could handle the manuscripts. Reliance on sloth of others always pays dividends!

It appeared that months later some members of the editorial board argued the papers were of poor quality and they investigated. However, some of the papers had already been published. The investigation revealed that the original proposers were not who they claimed to be. Now this strikes me as evidence of particular slothfulness on the part of the journals. If someone claims to be a senior person at a university, they will be listed on the University’s web page, usually with evidence to support the glowing claims. That is because if the person is any good, the University wants to take what credit it can. Now, if only I knew who these editors were, why I have a very important bridge to sell them.

Which raises the question, why do people do this? One reason suggested by the article is that the scammers offer a service to researchers who are not doing very well. For a payment, they will put the name on the paper. Oddly enough, a paper with many contributors from many places is often considered to be very good, because a lot of people will have sorted out the bad stuff. Nobody checks to see if the names really knew about the paper, so a genuine “big name” can be added. Now the researcher gets another paper from a “reputable journal” to add to their CV, which means they get help for their funding applications, or even keep their jobs. One criticism of that theory raised in the linked item was, “The papers are so obviously terrible, so why would you want them on your CV?” That reasoning is wrong because it carries an inherent assumption: those reviewing the fund application or the promotion/appointment lists actually read the papers. The CV lists a title. It may seem incomprehensible, but on its own that happens with a lot of reputable papers to those not directly involved in the field. As an example, here is the title of a paper “Single ion thermal wave packet analyzed via time- of-flight detection.” That, I must add, is a perfectly respectable paper, but how many readers would know what it was about just from the title? You would have to read the paper to know whether it is respectable, and you would need to know some physics. It would not be that difficult to write something about nanotechnology that looked vaguely respectable to those completely outside the field. All you have to do is take an existing paper and change some words, mainly nouns, but keep the verbs and important keywords.

So what should happen to stop this happening? The first question is, why are Springer and Elsevier being attacked? The answer is these are big commercial publishers, so it is money. The special issues make money without the need for particular effort. But I think the second issue is to examine why people do it? The procedures of funding research or employment must change so that the number of papers is meaningless. The third issue is that you hear that scientific papers are peer reviewed and hence have real value. What this farce shows is that peer review is a farce in many cases. But maybe that is for another time, but not next week.

My Introduction to the Scientific Method – as actually practised

It is often said if you can’t explain something to a six-year-old, you don’t understand.

I am not convinced, but maybe I don’t understand. Anyway, I thought I would follow from my previous post with an account of my PhD thesis. It started dramatically. My young supervisor gave me a choice of projects but only one looked sensible. I started that, then found the answer just published. Fortunately, only month wasted, but I had no project and supervisor was off on vacation. Head of Department suggested I find myself a project, so I did. There was a great debate going on whether the electrons in cyclopropane could delocalize into other parts of a molecule. To explain, carbon forms bonds at an angle of 109.5 degrees, but the three carbons of cyclopropane have to be formally at 60 degrees. In bending them around, the electrons come closer together and the resultant electric repulsions mean the overall energy is higher. The higher energy difference is called strain energy. One theory was the strain energy could be relieved if the electrons could get out and spread themselves over more space. Against that, there was no evidence of single bonds being able to do this.

My proposal was to put a substituted benzene ring on one corner, and an amine on the other. The idea was, amines are bases and react with acid, and when they do that the electrons on the amine are trapped. If the cyclopropane ring could delocalize electrons there was one substituent I could put on the benzene ring that would have different effects on that basicity depending on whether the cyclopropane ring did delocalize electrons or not. There was a test through something called the Hammett equation. My supervisor had published on this, but this would be the first time the equation might be used to do something of significance. Someone had tried that scheme with carboxylic acids, but with an extra carbon atom they were not very responsive and there were two reports with conflicting answers. My supervisor, when he came back, was not very thrilled with this proposal, but his best alternative was to measure the rates of a sequence of reactions for which I had found a report that said the reaction did not go. So he agreed. Maybe I should have been warned. Anyway, I had some long-winded syntheses to do.

When it came to reaching the end-position, my supervisor went to North America on sabbatical, and then sequentially looking for a new position in North America, so I was on my own. The amine results did not yield the desired result because the key substituent, a nitro group, reacted with the amine very quickly. That was a complete surprise. I could make the salt, but the solution with some amine quickly discoloured. However, in a fleeting visit my supervisor made a useful suggestion: react the acids in toluene with a diazo compound. While the acids previously had been too similar in properties in water, it turned out that toluene greatly amplified the differences. The results were clear: the cyclopropane ring did not delocalize electrons.

However, all did not go well. The quantum mechanical people who had shown the extreme stability of polywater through electron delocalization turned their techniques to this problem and asserted it did. In support, they showed that the cyclopropane ring stabilized adjacent positive charge. However, if the strain energy arose through increased electron repulsion, a positive charge would reduce that. There would be extra stability with a positive charge adjacent, BUT negative charge would destabilize it. So there were two possible explanations, and a clear means of telling the difference.

Anions on a carbon atom are common in organic chemistry. All attempts at making such an anion adjacent to a cyclopropane ring failed. A single carbon atom with two hydrogen atoms, and a benzene ring attached forms a very stable anion (called a benzyl anion). A big name replaced one of the hydrogen atoms of a benzyl anion with a cyclopropane ring, and finally made something that existed, although only barely. He published a paper and stated it was stabilized by delocalization. Yes, it was, and the stabilization would have come from the benzene ring. Compared with any other benzyl anion it was remarkably unstable. But the big names had spoken.

Interestingly, there is another test from certain spectra. In what is called an n->π* transition (don’t worry if that means nothing to you) there is a change of dipole moment with the negative end becoming stronger close to a substituent. I calculated the change based on the polarization theory, and came up with almost the correct answer. The standard theory using delocalization has the spectral shift due to the substituent in the opposite direction.

My supervisor, who never spoke to me again and was not present during the thesis write-up, wrote up a paper on the amines, which was safe because it never showed anything that would annoy the masses, but he never published the data that came from his only contribution!

So, what happened? Delocalization won. A review came out that ignored every paper that disagreed with its interpretation, including my papers. Another review dismissed the unexpected spectral shift I mentioned by saying “it is unimportant”. I ended up writing an analysis to show that there were approximately 60 different sorts of observation that were not in accord with the delocalization proposition. It was rejected by review journals as “This is settled” (that it was settled wrongly was irrelevant) and “We do not publish logic analyses.” Well, no, it seems they do not, and do not care that much.

The point I am trying to make here is that while this could be regarded as not exceptionally important, if this sort of wrong behaviour happens to one person, how much happens across the board? I believe I now know why science has stopped making big advances. None of those who are established want to hear anyone question their own work. The sad part is, that is not the only example I have.

Polymerised Water

In my opinion, probably the least distinguished moment in science in the last sixty years occurred in the late 1960s, and not for the seemingly obvious reason. It all started when Nikolai Fedyakin condensed steam in quartz capillaries and found it had unusual properties, including a viscosity approaching that of a syrup. Boris Deryagin improved production techniques (although he never produced more than very small amounts) and determined a freezing point of – 40 oC, a boiling point of » 150 oC, and a density of 1.1-1.2. Deryagin decided there were only two possible reasons for this anomalous behaviour:

(a) the water had dissolve quartz,

(b) the water had polymerised.

Since recently fused quartz is insoluble in water at atmospheric pressures, he concluded that the water must have polymerised. There was no other option. An infrared spectrum of the material was produced by a leading spectroscopist from which force constants were obtained, and a significant number of papers were published on the chemical theory of polywater. It was even predicted that an escape of polywater into the environment could catalytically convert the Earth’s oceans into polywater, thus extinguishing life. Then there was the inevitable wake-up call: the IR spectrum of the alleged material bore a remarkable resemblance to that of sweat. Oops. (Given what we know now, whatever they were measuring could not have been what everyone called polywater, and probably was sweat, and how that happened from a very respected scientist remains unknown.)

This material brought out some of the worst in logic. A large number of people wanted to work with it, because theory validated it existence. I gather the US navy even conducted or supported research into it. The mind boggles here: did they want to encase enemy vessels in toffee-like water, or were they concerned someone might do it to them? Or even worse, turn the oceans into toffee, and thus end all life on Earth? The fact that the military got interested, though, shows it was taken very seriously. I recall one paper that argued Venus was like it is because all its water polymerised!

Unfortunately, I think the theory validated the existence because, well, the experimentalists said it did exist, so the theoreticians could not restrain themselves from “proving” why it existed. The key to the existence is that they showed through molecular orbital theory that the electrons in water had to be delocalized. Most readers won’t see the immediate problem because we are getting a little technical here, but to put it in perspective, molecular orbital theory assumes the electrons are delocalized over the whole molecule. If you further assume water molecules come together, the firsr assumption requires the electrons to be delocalised, which in turn forces the system to become one molecule. If you cannot end up with what you assumed in the first place, your theoretical work is not exactly competent, let alone inspired.

Unfortunately, these calculations involve what are called quantum mechanics. Quantum mechanics is one of the most predictive theories ever, and almost all your electronic devices have parts that would not have been developed but for knowledge of quantum mechanics. The problem is that for any meaningful problem there is usually no analytical solution from the formal quantum theory generally used, and any actual answer requires some rather complicated mathematics, and in chemistry, because of the number of particles, some approximations. Not everyone agreed. The same computer code in different hands sometimes produced opposite results with no explanation of why the results differed. If there were no differences in the implied physics between methods that gave opposing results, then the calculation method was not physical. If there were differences in the physics, then these should have been clearly explained. The average computational paper gives very little insight to what is done and these papers were actually somewhat worse than usual. It was, “Trust me, I know what I’m doing.” In general, they did not.

So, what was it? Essentially, ordinary water with a lot of dissolved silica, i.e. option (a) above. Deryagin was unfortunate in suffering in logic from the fallacy of the accident. Water at 100 degrees C does not dissolve quartz. If you don’t believe me, try boiling water it in a pot with a piece of silica. It does dissolve it at supercritical temperatures, but these were not involved. So what happened? Seemingly, water condensing in quartz capillaries does dissolve it. However, now I come to the worst part. Here we had an effect that was totally unexpected, so what happened? After the debacle, nobody was prepared to touch the area. We still do not know why silica in capillaries is so eroded, yet perhaps there is some important information here, after all water flows through capillaries in your body.

One of the last papers written on “anomalous water” was in 1973, and one of the authors was John Pople, who went on to win a Nobel Prize for his work in computational chemistry. I doubt that paper is one that he is most proud of. The good news is the co-author, who I assume was a post-doc and can remain anonymous because she almost certainly had little control on what was published, had a good career following this.

The bad news was for me. My PhD project involved whether electrons were delocalized from cyclopropane rings. My work showed they were not however computations from the same type of computational code said it did. Accordingly, everybody ignored my efforts to show what was really going on. More on this later.