Too Damn Many People

We are in a population crisis.

Virtually every serious crisis we are experiencing now, from anti-immigrant attitudes, to climate change, lack of housing, homelessness, inequality, warfare, drought, desertification, traffic, scarcity of natural resources, and loss of wildlife, share a common root cause of overpopulation. Like any wonderful thing, it is the dose that makes something great turn into something less great.

The top line of damage is of course environmental destruction. In the last 50 years, the population of wild animals has fallen by half. CO2 in the atmosphere has doubled, which promises an eon of pain for the biosphere. The oceans are awash with trash, and all habitats from the arctic, to prairies, coral reefs, and rainforests are either being directly destroyed by humans and / or are being impaired indirectly by our global effects.

Summer arctic sea ice in dramatic decline.

Politically and socially, the idea that Europe should welcome millions of refugees from Africa and the Middle East, driven themselves by environmenal degradatation and overpopulation, and the conflicts they generate, is creating an understandable backlash. Just as global heating is reducing water and arable land, populations are growing all over these regions due to a modicum of medical and agricultural technology, combined with lack of human development. But is further human development the answer? From an environmental perspective, hardly- while development typically reduces birth rates, it explodes appetites and capacities to degrade the ultimate resource- the Earth- its minerals and biosphere.

An example is China. China carried out one of the most important environmental policies of all time when it instituted the one-child policy. It was, thanks to its draconian nature, effective in keeping population growth under control. Now China has a billion more people than the US, but it could easily have been two billion, in far more miserable condition. It played a big role in enabling the ensuing economic development, which has made China the biggest emitter of CO2 in the world, and generated countless other environmental problems, of global as well as local scope. They are building coal-fired power plants at a breakneck pace, and will be almost doubling worldwide coal-fired power capacity over the next decade or two. This is not driven by population, but by development of existing populations.

We are living far beyond the carrying capacity of the Earth, and our long-term choice is to either live sustainably or to have fewer people. Both seem impossible options, given that true sustainability is far more arduous than what any country has attempted to date, and is very hard to envision. Carrying capacity has many different aspects, from aesthetic features that come with a healthy biosphere, to critical minerals, water supply and agricultural capacity. Each of these has different relations to human population, and different elasticities based on our needs and technology. But we can safely say from the many ways we are degrading the global environment that we are well beyond many individual capacities, especially those that pertain to the biopshere in general, and animals other than ourselves.

Population is unfortunately, precisely the area where we care least about others. Our desires for family and legacy are very personal, often construed as a human right of some sacred or sovereign nature. But summed over the globe, it amounts to another tragedy of the commons, where my chastity merely makes room for someone else's profligacy.

There is no population bomb in the traditional sense. The agricultural technology we have, and the economic systems that drives its use, will insure all can be fed to some degree. There is a bomb, however, in a larger environmental sense. The degradation of the biosphere by humans is a slow-motion attack, as though several nuclear bombs were unleashed every year, rendering large areas uninhabitable, and sprinkling the rest of the globe with all sorts of trashy, choking fallout. These bombs are going off steadily and silently, year in and year out, till we will end up living in a global trailer park.

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Touch the Pressure Sensor

The revealing structure of one pressure-sensing protein complex.

The sensation of touch is perhaps the most elemental, and the most wide-spread, in nature. And detecting pressure doesn't just function in conscious sensation, but in all sorts of other processes such as, proprioception in muscles and joints, kidney function, red blood cell shape maintenance, blood pressure regulation, pain, bone maintenance, cancer cell invasion, neural development, and embryonic development generally, where bulging, shape changes, and migration are all guided by mechanisms that sense pressure inside and between cells.

Thus it is no surprise that we have numerous pressure sensors in our genomes, of various types. The sensors involved in hearing (TMC1 and TMC2) are different from a series of sensors involved in touch, (TREK-1), which are different from those responsible for organ shape and development. One thing they all share, however, is that they are cation channels. That means that deformations in the membrane they lie in, or other attachments they may have, get translated into a rush of potassium or calcium ions, out of or into the cell, respectively. This leads either to direct membrane depolarization (potassium ions), or signal propagation (calcium) via other proteins and channels.

A recent paper (review) detailed the interesting structure of PIEZO1, which is in a recently-discovered family of mechano-sensors that function in organ development and maintenance, conduct cations, mostly potassium, when activated, and directly (though briefly) depolarize membranes they reside in. While all membrane proteins are affected by membrane stretching, and there are simpler ways to translate mechanical stress into channel opening, PIEZO1 shows a rather intricate structure that allows exquisite sensitivity and control of its channel.

Top view, and side views of the PIEZO1 mechanosensory ion channel. In cells, the top faces the cytoplasm.

The first thing to notice is the dramatic, classic, maybe even Star-Treky, triskelion structure adopted by the trimeric protein. The authors note that they did not even see the entire protein, and that there should be twelve more helices extending out on each arm beyond those here that we can see, which are flapping in the breeze, so to speak. Second is the knot of protein in the center, above the plane of the rest of the structure. The actual channel is deep within the convergence zone of the three arms, so is far away from the protein knot, which extends intracellularly. This structure was derived from electron microscopy, which has begun to overtake X-ray crystallography as a method for structure determination, and the authors provide an averaged overview of what they were looking at, below.

Averaged electron micrographic view, without the inferred atomic modeling shown above. Scale bar is 10 nm.

Here, the arms are looking much more like a membrane interface, and the structure as whole clearly forms a cup that pre-deforms the membrane in a way that then makes the detection of membrane stretching even more sensitive than it would otherwise be. The authors spend much of the paper showing that this is the case- that in artificial vesicles, one can see PIEZO1 deforming the local membrane quite dramatically. One can easily see how this would make membrane stresses easier to sense.

Model of the channel (gray) surrounded by key protein structures, including negatively charged Glutamic acid (E) at the most constricted point, where opening is predicted upon membrane tension.

As for the actual channel, they provide a structure that narrows down to nothing at the bottom (E2537, showing the red negatively charged ends of glutamic acid). Clearly their model is of a closed version, which makes sense given the relaxed conditions used for visualization. Opening awaits some stretch on the overall structure that will pull these protein structures apart slightly, but not too much- enough to allow a four Ångstrom opening, as estimated from studies of the channel's conductance.

Another key part of the structure is the long helix running from the bottom, near the ion channel to about halfway along each triskelion arm. They seem to be key "beams" that transmit leverage from tension-induced membrane flattening towards the center nexus where this channel constriction is so obvious. As the authors put it ("TM" refers to transmembrane alpha helix domain, of which there are 38 in all per monomer):

"At first consideration a force directed along the triskelion arms toward the center of the trimer, associated with flattening of Piezo’s arms, might be expected to constrict the pore further. However, given that TM37-38 are domain-swapped relative to TM1-36, such a force will more likely push the ‘swapped’ pore-lining helices away from the center and open the pore."

That is to say, the beam helices at so long and subtly connected to the pore that they push cross-wise from the three directions, pulling the channel open instead of pushing it closed. This putative mechanism helps to some degree also to isolate the pore from the activating force, limiting its opening so that it can be ion-selective and have high, but limited, conductivity while open, all with super-high sensitivity. There are examples of stretch activated channels from bacteria whose function is to relieve turgor pressure stress, and whose opening is virtually unlimited under stress, becoming completely non-selective in what they allow through, which is very effective for their stress-relieving role.

This is a beautiful and informative structure. It shows yet again that underlying the magic and mysteries of biology is always structure and chemistry. Defects in these types of channels are responsible for a wide range of problems. Complete deletion of this gene (PIEZO1) in mice is rapidly lethal soon after the heart begins to beat, since the nascent vasculature is deranged, not being able to sense fluid pressures. The same gene is key for neural cell development and pathfinding. It also plays a central role in helping red blood cells know and regulate their pressure status, which is key to their function and survival as they squeeze through tight spots and get jostled by turbulent flows.

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Vietnam: the Good Fight

Maybe not wise or practical, but morally, Vietnam was justified, especially in hindsight.

It was culturally traumatic, and militarily disastrous. It was a collossal mistake and soure of bitterness for decades. The Vietnam war remains a touchstone of shame and division in the US; a toxic and momentous legacy in Vietnam itself. I saw the first several episodes of Ken Burns's treatment of how we got into that war, and found it very interesting, historically. The documentary's tone was drenched with sadness and tragedy. But it also let some significant facts leak in.

The problem was that the government of South Vietnam was a mess. It was essentially a successor state to the French colonial regime, while the government of the North was the successor of the successful independence fight, led by the communists / Viet Minh. The North capitalized on its credibility with effective PR, and before you know it, the South was overrun with Viet Cong and related insurgents, sympathisers, and agents, especially in the rural areas. And all seem to agree that Ho Chi Minh would have won the re-unification elections that were never held. But the North was not all it seemed. It was also a brutal communist state- a predator state. According to Wikipedia:

"The Socialist Republic of Vietnam, along with China, Cuba, and Laos, is one of the world's four remaining one-party socialist states officially espousing communism. Its current state constitution, 2013 Constitution, asserts the central role of the Communist Party of Vietnam in all organs of politics and society."

This, two decades after the fall of the Soviet Union, and four and a half since the end of the American War (Vietnam War). This is a durable system! While Vietnam has lately followed China's lead in adopting limited capitalism, we should not imagine that it is a free or prosperous country. It remains very much in the totalitarian camp.

At the time, the US had just been through a similar war, in Korea, another tough slog defending the South from a blitzkrieg by the North. In that case, the US and the South were successful, and now South Korea has transformed into a happy, rich country, exporting K-Pop off an assembly line that seems to have no limit. Meanwhile, North Korea has remained stable in its way- stably dictatorial and desperately poor.

These are the conditions that the US was consciously defending South Vietnam from, and we were very right to do so. Unfortunately, the French had so thoroughly loused things up, between their import of Catholicism, their moral blindness in denying the Vietnamese what they had themselves had just fought World War 2 to regain, their futile war in Vietnam, and their organization of the South under Emperor Bao Dai and Prime minister Ngo Diem, that propping up the South proved impossible. The US did not want to replicate the colonialism of the French, just to keep the South out of the communist hands. But as it turned out, we would have had to do so and run the whole country, indeed on a rather brutal basis, if we really had wanted to save the situation. The problem was never military, but political- the people of the South were so mistreated by their government that their will to fight, in the myriad ways one has to fight in a civil and a guerrilla war, had dropped to zero.

So I think we should recognize that the US was doing a noble and proper thing in this war. Leaving the South defenseless, or cutting and running after we had gotten involved, would have been expedient, but not morally good. However, in hindsight, those would have been the wisest policies, saving everyone a great deal of death and waste. But that is a different point, both from the moral perspective, and given that hindsight comes too late. We can grant that many people, not least of whom were John Kennedy and Lyndon Johnson, recognized to some degree the bad, almost futile situation they were getting into. But while we can doubt their wisdom in not following their own analyses with greater discipline and political courage, their moral purposes were not bad ones.

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