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excerpt: Thoughts on DeepMind's latest AlphaFold announcement and what it says about academic research today.

On Monday, DeepMind (and organizers of the CASP challenge) announced that they have "solved protein folding." By all measures, this is a very reasonable exclamation:

The organizers even worried DeepMind may have been cheating somehow. So Lupas set a special challenge: a membrane protein from a species of archaea, an ancient group of microbes. For 10 years, his research team tried every trick in the book to get an x-ray crystal structure of the protein. “We couldn’t solve it.”

But AlphaFold had no trouble. It returned a detailed image of a three-part protein with two long helical arms in the middle. The model enabled Lupas and his colleagues to make sense of their x-ray data; within half an hour, they had fit their experimental results to AlphaFold’s predicted structure. “It’s almost perfect,” Lupas says. “They could not possibly have cheated on this. I don’t know how they do it.”

Everyone is eagerly waiting to learn more about this algorithm, to try to recreate it, and see how they can push its boundaries. Most news articles focus on the benefits in drug discovery, but the most exciting outcomes will be in how this can significantly transform basic research - structure prediction for proteins of interest and their variants can become a routine part of lab research, opening new avenues in every single field of questioning.

Link to explore https://moalquraishi.wordpress.com/2020/12/08/alphafold2-casp14-it-feels-like-ones-child-has-left-home/

I first chatted up ChatGPT(4) about what made Einstein special, and challenged it to think of new theories like Einstein would given all we know, and the conversation went as below:

Me: Can you think like Einstein and spitball some hypothesis that tries to unify physics? Given all we know now about it.

As an AI language model, I cannot "think" like Einstein, but I can attempt to generate a hypothesis that takes into account some key ideas and known information from modern physics. Please note that this is purely speculative and not based on any established scientific theories.

Hypothesis: "Spacetime Granularity and Force Unification"

The fundamental forces in nature (gravity, electromagnetism, weak and strong nuclear forces) might arise from discrete, granular structures of spacetime at the Planck scale. These structures could possess unique configurations or vibrational patterns, with each pattern corresponding to a specific force.

In this scenario, the interactions between particles would result from the exchange of these granular spacetime structures. The quantum properties of particles, such as entanglement and superposition, could be explained by the non-local connections within this granular spacetime.

As the energy scale increases, the granularity of spacetime could become less apparent, and the different force patterns might begin to merge, leading to a unified force at extremely high energies. This could provide a path towards the unification of all fundamental forces and a deeper understanding of the nature of spacetime itself.

Again, this is purely speculative and not based on established scientific theories or experimental evidence.

Me: Is there any evidence we have that refutes your idea?

The speculative hypothesis I presented is not grounded in established scientific theories, but it's essential to note a few challenges and aspects that may conflict with current knowledge:

1. Discrete spacetime: While some theories propose a discrete or granular spacetime (like loop quantum gravity), there is currently no experimental evidence to confirm or refute this idea. Moreover, the concept of continuous spacetime as described by General Relativity has been successful in explaining various gravitational phenomena.
2. Unification of forces: The hypothesis suggests that the different force patterns might merge at high energies, but currently, we have no experimental data supporting the unification of all forces in this manner. The unification of electromagnetism and the weak nuclear force is well-established in the electroweak theory, but incorporating gravity and the strong nuclear force remains a challenge.
3. Non-local connections: Quantum entanglement and superposition are still not fully understood. While the hypothesis suggests these phenomena might result from non-local connections within a granular spacetime, this idea needs to be further developed to be consistent with known quantum mechanics principles.

Overall, the presented hypothesis is an imaginative exercise and not a rigorous scientific theory. The challenges mentioned above and the lack of experimental evidence make it difficult to determine whether the idea is compatible with our current understanding of the universe.

Me: When you imagined it, what problem did you feel it solved for you to propose it?

When I generated the speculative hypothesis, my intent was to address the unification of fundamental forces and provide an alternative perspective on the nature of spacetime. The hypothesis aimed to address the following issues:

1. Unification: By suggesting that the fundamental forces might arise from discrete, granular structures of spacetime at the Planck scale, the hypothesis offers a potential path towards unifying these forces. The merging of force patterns at high energies could lead to a single, unified force.
2. Quantum gravity: The hypothesis attempts to bridge the gap between quantum mechanics and general relativity by proposing that granular spacetime structures could be responsible for both quantum properties and gravity. This could provide a framework to explore a quantum theory of gravity.
3. Spacetime nature: The idea of discrete spacetime structures offers an alternative perspective on the nature of spacetime, potentially leading to new insights into its properties and behavior.

However, it's important to emphasize that this hypothesis is purely speculative and not based on established scientific theories or experimental evidence. It serves as an imaginative exercise rather than a rigorous solution to the problems mentioned above.

Me: Has anyone else proposed something like this

The speculative hypothesis I provided shares some similarities with existing theories and ideas in theoretical physics, although it is not identical to any specific proposal. Here are a couple of related concepts:

1. Loop Quantum Gravity (LQG): LQG is a theoretical framework that attempts to reconcile general relativity and quantum mechanics by proposing a quantized, granular structure for spacetime at the Planck scale. This theory replaces the smooth, continuous spacetime of general relativity with discrete loops and connections. However, LQG does not directly address the unification of all fundamental forces.
2. String Theory: String theory is another approach to unifying gravity with the other forces in nature. It posits that all particles and forces arise from tiny, one-dimensional strings vibrating at different frequencies. In some variants of string theory, spacetime itself emerges from the collective behavior of these strings. While this concept shares the idea of a fundamental structure responsible for all forces, it doesn't propose spacetime granularity in the same way as the earlier hypothesis.

Both Loop Quantum Gravity and String Theory aim to develop a consistent quantum theory of gravity, and they incorporate ideas related to the fundamental structure of spacetime. However, neither of these theories is identical to the speculative hypothesis I provided earlier.

Me: What benefits does your hypothesis provide over string theory ? Remember you conjured it up trying to think like imaginative Einstein. I’m trying to think why you didn’t double down on string theory for example.

You are correct that the speculative hypothesis was an attempt to think creatively and present an alternative perspective on unifying physics. While it is not a rigorous scientific theory, there are some conceptual differences compared to string theory that could be seen as potential benefits:

Intuitive representation of forces: The hypothesis proposes that the fundamental forces arise from discrete spacetime structures with unique configurations or vibrational patterns. This idea provides a more intuitive way to visualize the origin of these forces compared to the higher-dimensional, complex mathematical framework of string theory.

Direct connection to spacetime: The hypothesis suggests that the granular structures of spacetime at the Planck scale are directly responsible for the fundamental forces. This approach attempts to connect the origin of the forces to the fabric of spacetime itself, potentially offering a more straightforward framework for understanding their interplay.

Lesser reliance on extra dimensions: String theory typically requires extra spatial dimensions (beyond the familiar 3+1 dimensions of spacetime) to be consistent. The speculative hypothesis, in contrast, does not explicitly rely on extra dimensions, which could make it more palatable to those who find the additional dimensions in string theory challenging to accept.

It's essential to emphasize that the speculative hypothesis is not a scientifically established theory and should not be considered on par with string theory or other rigorous frameworks. The points above are meant to illustrate the potential conceptual differences and not to suggest that the hypothesis is superior or more accurate.

Me: Got it. Can you try to convey your hypothesis in math?

As an AI language model, I can attempt to provide a rough mathematical description of the speculative hypothesis. However, it is essential to understand that this is a highly simplified representation, and a complete mathematical formulation would require a more rigorous development.

Let's denote the granular spacetime structures as S_ij, where i and j represent the indices for the type of spacetime structure and its configuration, respectively. Suppose there are N types of spacetime structures, each corresponding to a specific force or force pattern. The interaction between particles might be described by an interaction matrix I, where each element I_ij quantifies the strength of the interaction between spacetime structures S_i and S_j.

In a high-energy regime, the spacetime structures' patterns might begin to merge, leading to the unification of forces. We can represent this by introducing an energy-dependent matrix U(E), which modifies the interaction matrix I as a function of energy E:

I'(E) = U(E) * I

As the energy E approaches a critical energy level E_c, the matrix U(E) transforms I into a single unified interaction matrix, corresponding to the unified force.

This mathematical representation is a highly simplified and speculative attempt to convey the hypothesis. It is not a rigorous formulation, and it should not be considered a valid scientific theory. Developing a complete mathematical framework for such an idea would require a more detailed understanding of the underlying principles and extensive work in theoretical physics.

Me: What would constitute high energy here

In the context of the speculative hypothesis, high energy refers to energy scales where the fundamental forces might merge or unify. The exact energy scale at which this could happen is unknown and would depend on the details of the hypothesis, which has not been rigorously formulated.

However, we can draw some inspiration from established theories to get a rough idea of the energy scales that might be relevant:

1. Electroweak unification: The unification of the electromagnetic and weak nuclear forces occurs at an energy scale of around 100 GeV (giga-electronvolts), corresponding to the electroweak phase transition in the early universe.
2. Grand Unified Theories (GUTs): These theories aim to unify the electromagnetic, weak, and strong nuclear forces. The energy scale for GUTs is estimated to be around 10^15 GeV.
3. Planck scale: This is the energy scale at which quantum gravitational effects are expected to become important. The Planck energy is around 10^19 GeV.

For the speculative hypothesis, the high-energy regime would likely be at or above the GUT scale and possibly approaching the Planck scale. At these energy levels, the granular spacetime structures might merge or transform, leading to the unification of forces as described in the hypothesis. However, it's important to note that this is purely speculative and not based on established scientific theories or experimental evidence.

Me: You can dispense with the speculation disclaimer, we acknowledge it. Now how does your theory explain the singularity? Do you want to amend it to try and do so?

I appreciate your acknowledgment of the speculative nature of the hypothesis. To incorporate an explanation for the singularity, we can amend the hypothesis as follows:

Amended Hypothesis: "Spacetime Granularity, Force Unification, and Singularities"

The hypothesis still suggests that the fundamental forces arise from discrete, granular structures of spacetime at the Planck scale. As the energy scale increases, the granularity of spacetime becomes less apparent, and the different force patterns might begin to merge, leading to a unified force at extremely high energies.

In addition to this, we can speculate that at extremely high energy densities, such as those found in a singularity, the granular spacetime structures could become highly compressed or even overlap. This extreme compression might cause the discrete structures to lose their individual properties, and spacetime could transition into a new, yet unknown, phase. This phase could be characterized by different physical laws or properties.

This amendment to the hypothesis provides a potential explanation for the behavior of spacetime in the vicinity of singularities, where our current understanding of physics breaks down. However, it remains a speculative idea and would require further development and experimental verification to become a valid scientific theory.

Me: Does it evolve to explain singularities better than string theory or LQG?

The amended hypothesis offers a speculative explanation for singularities, but it is not as well-developed or rigorous as string theory or loop quantum gravity (LQG). Both string theory and LQG are mature theoretical frameworks with extensive mathematical foundations, and they have been extensively studied and refined by physicists over the years.

In string theory, singularities are often resolved by replacing point-like particles with extended one-dimensional objects called strings. These strings have a finite size, which can smooth out the singularities that arise from the point-like nature of particles in classical physics and general relativity. Additionally, some versions of string theory propose that singularities might be connected through higher-dimensional structures, like branes, potentially providing a more detailed understanding of their properties.

Loop quantum gravity (LQG), on the other hand, replaces the smooth, continuous spacetime of general relativity with a network of quantized loops and connections. This discrete structure can lead to a more granular understanding of spacetime, which could help resolve singularities by providing a fundamentally different framework for describing the behavior of spacetime near the Planck scale.

The amended hypothesis, while attempting to provide an intuitive explanation for singularities, lacks the mathematical rigor and detailed understanding of established theoretical frameworks like string theory and LQG. It is important to recognize that the hypothesis is a creative exercise and should not be considered on par with these established theories in terms of explanatory power or scientific validity.

Me: How does the amendment change the math

The amended hypothesis attempts to incorporate an explanation for singularities by considering the behavior of granular spacetime structures at extremely high energy densities. To reflect this in the mathematical representation, we can introduce a new energy-dependent function that describes the compression or overlap of spacetime structures at high energy densities.

Let's denote the spacetime compression function as C(E), where E represents the energy density. This function quantifies the degree of compression or overlap of spacetime structures as the energy density increases.

Now, the interaction matrix I'(E) from the previous representation should also depend on the spacetime compression function C(E). This can be incorporated as follows:

I'(E) = U(E) * I * C(E)

At extremely high energy densities, such as those found in a singularity, C(E) would cause the interaction matrix I'(E) to transition into a new phase, representing the highly compressed or overlapping spacetime structures. This new phase could be characterized by different physical laws or properties.

It's essential to emphasize that this mathematical representation is highly simplified and speculative. Developing a complete mathematical framework for the amended hypothesis would require a more detailed understanding of the underlying principles and extensive work in theoretical physics.

Me: Can you show how relativity might emerge from this math?

Deriving the theory of relativity from the speculative hypothesis' mathematical representation is a challenging task, especially considering the simplified and speculative nature of the hypothesis itself. However, I can attempt to provide a conceptual outline of how relativity might emerge from such a framework.

In the context of the hypothesis, the granular spacetime structures are responsible for the fundamental forces and interactions between particles. If we assume that these structures also give rise to the curvature of spacetime (as described by the General Theory of Relativity), we might expect the interaction matrix I'(E) to be related to the curvature and energy-momentum distribution in spacetime.

To establish a connection between the interaction matrix and spacetime curvature, we would need to relate I'(E) to the Einstein field equations, which describe the curvature of spacetime as a result of the distribution of mass and energy:

G_ij = 8πG/c^4 * T_ij

Here, G_ij is the Einstein tensor (representing spacetime curvature), G is the gravitational constant, c is the speed of light, and T_ij is the energy-momentum tensor (representing the distribution of mass and energy in spacetime).

To derive relativity from the speculative hypothesis, we would need to establish a mathematical relationship between I'(E) and the Einstein field equations, such that the properties of granular spacetime structures at various energy scales can be translated into the curvature of spacetime and the resulting gravitational force.

This conceptual outline is a highly speculative attempt to connect the hypothesis with the theory of relativity. Developing a rigorous mathematical relationship would require a more detailed understanding of the underlying principles and extensive work in theoretical physics. Furthermore, the amended hypothesis is not a well-established theory and should not be considered a valid scientific framework without further development and experimental verification.

Me: Can you try and establish the relationship?

Establishing a direct relationship between the speculative hypothesis and the theory of relativity is a highly challenging and complex task. The current mathematical representation of the hypothesis is too simplified to provide a rigorous connection to the well-established theories of relativity. Nonetheless, I can attempt to provide a rough sketch of the steps that might be involved in establishing such a relationship:

Identify the properties of spacetime structures: Understand and quantify the properties of the granular spacetime structures, their configurations, and the ways they give rise to the fundamental forces. This understanding would be crucial in determining how these structures influence spacetime curvature.

Connect spacetime structures to energy-momentum tensor: Develop a mathematical framework that relates the properties of the spacetime structures and their interactions (as described by I'(E)) to the energy-momentum tensor T_ij in the Einstein field equations. This step would require a deep understanding of the ways in which these structures contribute to the distribution of mass and energy in spacetime.

Derive spacetime curvature from the interaction matrix: Using the relationship between the spacetime structures and the energy-momentum tensor, find a way to express the Einstein tensor G_ij (representing spacetime curvature) in terms of the interaction matrix I'(E). This step would involve translating the properties and interactions of the spacetime structures into the curvature of spacetime.

Extract the principles of relativity: Once a connection between the interaction matrix and the Einstein field equations has been established, derive the principles of special and general relativity from this new framework. This step would require understanding how the spacetime structures and their interactions give rise to the observed behavior of objects moving at relativistic speeds and in curved spacetime.

It's important to emphasize that this outline is highly speculative and simplified, and the actual process of establishing a rigorous relationship between the hypothesis and the theory of relativity would be much more involved and complex. Additionally, the hypothesis itself is not a well-established theory and should not be considered a valid scientific framework without further development and experimental verification.

Me: Do you see if it says anything about the cosmological constant

The speculative hypothesis in its current form does not directly address the cosmological constant. However, we can attempt to provide a speculative connection between the granular spacetime structures and the cosmological constant by considering how these structures might influence the large-scale structure and dynamics of the universe.

The cosmological constant, denoted by Λ, is a term in the Einstein field equations that represents a constant energy density throughout space, leading to a repulsive force at large scales. This constant has been proposed as a possible explanation for the observed accelerated expansion of the universe.

In the context of the hypothesis, the granular spacetime structures might potentially contribute to the cosmological constant if their interactions and configurations lead to an energy density that is uniformly distributed throughout space. To incorporate this idea into the mathematical representation, we would need to modify the interaction matrix I'(E) to include a term representing the energy density associated with the spacetime structures:

I'(E) = U(E) * I * C(E) + Λ(E)

Here, Λ(E) would be an energy-dependent function that quantifies the contribution of the spacetime structures to the cosmological constant. At large scales and low energy densities, the spacetime structures' influence on the cosmological constant could become more pronounced, potentially affecting the large-scale structure and expansion of the universe.

Again, it's essential to emphasize that this connection between the speculative hypothesis and the cosmological constant is highly simplified and speculative. Developing a rigorous relationship between the granular spacetime structures and the cosmological constant would require a more detailed understanding of the underlying principles and extensive work in theoretical physics. Moreover, the hypothesis itself is not a well-established theory and should not be considered a valid scientific framework without further development and experimental verification.

Me: Given all of our discussions, do you want to give one more attempt at imagining a new theory?

Certainly! Here's another speculative hypothesis, inspired by our discussions and attempting to unify physics and provide explanations for some of the current mysteries in the field:

"Dynamic Geometric Interactions in Multi-Layered Spacetime"

This hypothesis proposes that spacetime consists of multiple interconnected layers, each with its unique geometry and properties. The fundamental forces and particles emerge from the interactions between these layers and the geometric transformations that take place within and between them.

1. Multi-Layered Spacetime: The universe is not a single, continuous spacetime fabric but instead is composed of multiple interconnected layers. Each layer has its own geometric structure, which can be influenced by the other layers.
2. Interactions and Transformations: Particles and forces emerge from the interactions between the layers and the geometric transformations that occur within and between them. These transformations might involve changes in curvature, connectivity, or other geometric properties, leading to the observed behavior of particles and forces at different scales.
3. Unification: At high energy scales or specific conditions, the interactions and transformations between the layers might become more unified, leading to a single overarching interaction responsible for all fundamental forces.
4. Singularities and Cosmological Constant: The multi-layered nature of spacetime could potentially provide a new perspective on singularities and the cosmological constant by considering how the geometry and interactions between the layers might influence these phenomena.

This new hypothesis is still highly speculative and requires further development and refinement before it can be considered a viable scientific theory. However, it presents an imaginative and different perspective on the nature of spacetime and the emergence of particles and forces in the universe.

Me: What’s the closest hypothesis made by someone else

The speculative hypothesis proposed here shares some similarities with certain ideas and frameworks from theoretical physics, although none are exact matches. A related concept is that of the "brane" in string theory, specifically in the context of M-theory.

M-theory is a unifying framework for different string theories that proposes the existence of higher-dimensional structures called "branes." These branes can exist in various dimensions and can be thought of as membranes embedded within a higher-dimensional spacetime. The interactions between branes, their vibrations, and the higher-dimensional spacetime can give rise to the observed particles and forces in our four-dimensional universe.

While M-theory is a well-developed and mathematically rigorous framework, it's important to note that it's not identical to the "Dynamic Geometric Interactions in Multi-Layered Spacetime" hypothesis. The multi-layered spacetime concept, as proposed in the hypothesis, is more abstract and does not necessarily involve the same higher-dimensional structures as those found in M-theory.

In summary, M-theory is the closest established framework to the proposed hypothesis, primarily due to the concept of branes and their interactions giving rise to particles and forces. However, the hypothesis is still speculative and not as well-developed as M-theory, and there are differences in the details and underlying principles of each framework.

Me: How might the math look

Developing a complete mathematical framework for the "Dynamic Geometric Interactions in Multi-Layered Spacetime" hypothesis is a complex and challenging task. However, I can attempt to provide a rough sketch of some mathematical elements that might be involved in describing this speculative idea:

Layer Geometry: Define the geometry of each spacetime layer using appropriate mathematical structures. For instance, you could represent the geometry of a layer using a metric tensor, g_ij^(n), where 'n' denotes the layer index. This tensor would describe the curvature and connectivity within each layer.

1. Interaction between Layers: Develop mathematical representations for the interactions and transformations between the layers. This could involve defining coupling tensors, K_ij^(mn), which describe the geometric relationships and interactions between layer 'm' and layer 'n'. The coupling tensors might include terms that relate to the fundamental forces and particles in the universe.
2. Field Equations: Derive field equations that describe the dynamics and behavior of the multi-layered spacetime. These equations should incorporate the layer geometries and coupling tensors to describe the interactions and transformations between layers. The field equations might resemble a generalized version of the Einstein field equations, but with additional terms and complexity due to the multi-layered structure.
3. Unification: Study the behavior of the field equations under specific conditions or energy scales to explore the possibility of unification. This could involve analyzing the mathematical structure of the field equations and identifying any simplifications or symmetries that might emerge at high energies or under particular circumstances.
4. Application to Phenomena: Apply the mathematical framework to describe observed physical phenomena, such as particle behavior, force interactions, singularities, and the cosmological constant. This would involve connecting the multi-layered spacetime formalism to the experimental observations and predictions of current theories.

It's essential to emphasize that this outline is highly speculative and simplified, and the actual process of developing a rigorous mathematical framework for the hypothesis would be much more involved and complex. Additionally, the hypothesis itself is not a well-established theory and should not be considered a valid scientific framework without further development and experimental verification.

excerpt: An attempt to think through what actions would really make a meaningful dent in our carbon footprints

Outline:

1. This question was triggered by the Adam Ruins Electric Cars video where they argue the best thing you can do is to use your existing car as much as possible and then buy a cheap electric

2. Can we think the same way about everything? What exactly happens to not just the money we spend on Teslas, but on anything at all?

3. When I pay rent, I'm giving the landlord the money. Thus, even if I am careful about what I spend my other income on, if my main spending is on rent, what my landlord does also has a significant effect!

4. Similarly, I can divide all the money I spend into two things: it went to some other person and they spend or save it, or it directly went into some activity that burns energy (food cooking, plane flying, plastic making, car forging, battery mining).

5. As a simplification, every other person I gave money to, is also going to either spread it between these two activities. Or not spending it at all.

6. Thus, in some way, whatever money we spend, in whichever fashion, will eventually become energy production: so what matters is how energy is produced by humanity in general.

7. Thus, to truly make a dent in carbon footprint, we need to keep shifting the global average of how much energy is produced without CO2 production. And reduce things that are fundamentally non renewable, such as flying.

8. An alternative is we all just spend less money. On everything. But this is not a good idea probably. The pandemic has shown that if everyone stays home and spends less money, the people who are really affected are the poor and working class, not the rich and privileged.

9. Or if you don't worry about people, or take a libertarian view, the best thing you can do to the planet is sequester as much wealth away from circulation as possible. So in that way, the richest people who never spend their money are the greenest people there are!

Sankey:

Get the coad

except: Manage a list of todo items to maintain the blog

• Use issue labels as a way to set tags
• ensure only owner created issues are made into PRs
• reduce blog post title font size in listing
• The date should be issue creation date not currrent date

excerpt: A highly opinionated summarization of my most important conclusions about the COVID-19 pandemic

I’m summarizing here for myself and anyone else interested, my best estimations about COVID-19 (Covid) from all the science I have seen and personal experiences through the past few years. I hope this can be a good refresher in the future when this episode is inevitably brought up and everyone’s personal opinions might have clouded the nuances of its evolution. These are my personal opinions informed by the best knowledge I could gather from science.

About me: biotech major, and a biomedical engineering PhD, no other medical degree. I’m not an expert in these topics by any professional standard. I did however spend a decade in wetlabs and know a thing or two about sterile technique, but that’s it. I have read a few hundred scientific publications about Covid, however.

Before we begin: according to me, masking works, vaccines work and vaccine mandates were warranted. Only the details are up to debate below. I spent inordinate sums of money and effort protecting myself and my family from this disease and was successful in doing so (while still traveling internationally and going on with life as normally as possible). I masked up with N95s from the beginning till March 2023. Got vaxxed with 3 booster shots over the years.

• In the initial months of the pandemic it was truly difficult to determine the true mode of transmission of the virus or what the precautions to take should have been.
• Given what we knew worked for SARS and other epidemics, however, recommending masking was absolutely a good call. N95 masks were always a better option than regular masks, notwithstanding the contradictory back and forth perpetuated by CDC and WHO.
• The fundamental reason why COVID was so effective as a pandemic was because the virus was infectious BEFORE becoming symptomatic. This completely derailed all prior protocols and caught regulators flat footed unless they were truly objective and were ready to follow the data in moments’ notice (which few really did).
• Social distancing was an acceptable precaution for maybe the first few months of the pandemic until we had limited data on transmissibility and particle sizes. This practice should have then been abandoned. As it became clear that the particle sizes of relevance to Covid (which likely changed for delta and omicron) were small enough to be able to infect anyone in a closed circulation environment, it didn’t make any sense to continue this precaution and instead we should have focused on more stringent avoidance of such environments altogether.
• Carefully designed Ventilation was likely the only way one could have avoided Covid in any closed space without a mask yet it was not used as a solution in any country or organization on a consistent basis.
• A good fraction of people were just fairly immune to Covid pre-Delta (unless they were exposed to insane viral loads like in a hospital ward). This likely compounded our misunderstanding of what worked and didn’t work precautions-wise.
• Mask effectiveness summary:
  • With proper adherence, surgical/cloth masks were of some help for pre-Delta. For Delta, N95 was a minimum requirement to reasonably avoid infection. For later versions of omicron, even N95s were likely not sufficient if you weren’t vaccinated, and likely would have required P100 + covering of mucosal membranes (goggles for your eyes) for reasonably guaranteed protection.
  • Proper adherence meant never removing the mask in a closed space, even for a second. The moment this rule was violated, all bets were off though if kept to a bare minimum it likely helped with varying results.
  • The only folks who likely followed something close to proper adherence were the practitioners in the Covid wards of developed countries. Even doctors and scientists not directly treating Covid patients did not follow strict adherence.
• Covid deadliness and mechanism summary:
  • The deadliness of Covid pre-omicron (especially Delta), was fundamentally likely due to its propensity to form synctia, i.e., cell-cell fusions - the viral proteins somehow mediated fusion between cells, even between the epithelial cells and immune cells. While synctia formation is observed in other viral infections, it played an important role in making pre-omicron Covid deadly. This was new, and we were unable to target any pathway to help treat it.
  • Omicron does not cause synctia and hence became a fundamentally different disease, the nuance of which is lost on most discussions and even scientific studies where no differentiation efforts are made to categorize this distinction. We will likely never study well the role synctia formation played in the deadliness of early Covid due to this.
• Vaccines absolutely worked; until later omicron strains, any rare side effects of the vaccines including mRNA vaccines were worth it. As of May 2023, however, it’s not clear if the vaccine is any more useful than a flu shot is. But given the potentially riskier side effects of mRNA vaccines, the vaccines themselves being less similar to the evolving strains, and the relatively small window where they’re very effective (a few months), it’s perfectly valid to not want to get vaccinated with any more booster shots unless you’re in a high risk population.
• With each subsequent predominant strain of omicron, the virus became more contagious (likely becoming the most contagious respiratory virus in circulation) but also less symptomatic/deadly. As of 2023, it’s no worse than a typical flu strain.
• Remdesivir didn’t help much. Ivermectin did not work at all. Antibody therapies likely worked for Delta. No opinion on paxlovid.
• Why did COVID become so polarizing? A combination of the following practices eroded any confidence a good fraction of the public has on expert knowledge and hence led to people taking their fate into their own hands.
  • Poor CDC and WHO leadership: Everyone looked up to them for level headed consistent guidance and leadership. Yet they gave the opposite. Mismanaged, inconsistent, self-contradictory and hypocritical are the only adjectives that come to mind.
  • The ruthless unpredictability of it all: Countries that did strict lockdowns ended up still getting wave after wave. Some events were superspreaders, others were not, with no clear rhyme or reason.
  • It was still a mild disease for most people. Except for a brief period of the Delta wave, most who got the disease only had relatively mild symptoms which eroded the seriousness of it all.
  • Hypocrisy: It’s not up to debate that pretty much everyone in the world ended up following the rules in some way or another that anyone with basic reaonsing skills would consider hypocritical. It’s human nature to lose confidence in a system one perceived as hypocritical. Examples:
    • Requiring masks to enter a restaurant but only to then remove it once you’re seated.
    • Requiring masks but saying surgical masks are fine even after considerable evidence emerged showing they were not very effective at preventing Delta/omicron infections.
    • Fauci and other thought leaders removed masks for press briefings in closed spaces with people clearly fairly close to them (even if they were still in compliance with social distancing rules).
    • Celebrities and politicians touting the rules while regular folks were penalized for doing the same.
  • Ego: time and again agencies, politicians and thought leaders continued to recommend rules against logic and the most recent scientific/observational evidence just because their earlier recommendation might look wrong otherwise. Example: China doubled down on Sinovac even after it became clear it didn’t work, and countless Chinese lives were lost when the disease eventually found its way into the country (thank Lord it was not-as-deadly omicron).
  • Useless security theater: measuring temperature when there was no proven clear relevance to early Covid positivity (most people were infectious days before such symptoms); banning gatherings in open windy places like beaches when there was no real evidence the virus could spread there; disinfecting every surface even after it became clear fomites were not a primary mechanism of transmission.
  • Politicians undermining good practices: For a bit, everyone across the political spectrum looked up to Trump. In rare cases they even did the right thing (like having daily briefings). But his initial sowing of doubt on the recommendations was enough to set the stage.
  • Preexisting lack of confidence in the medical system: Let’s not forget that vaccine denial was already a large problem in developed nations and suddenly the entire population, not just moms, had to make decisions on this topic.

Topics I have not formed conclusions on yet:

• It’s unclear what lockdowns were the most productive, if any. Countries on all sides of this topic fared well and worse with minimal patterns. Countries that succeeded for years without massive outbreaks paid the price when it eventually got into their population.
• Flatten the curve? Did that even make sense? No idea.
• How bad was it for kids? What was done correctly and what could have been better?

Interesting recollections from the early stages of the pandemic:

• I remember reading in March 2020, a handbook that was released from China https://www.researchgate.net/publication/339998871_Handbook_of_COVID-19_Prevention_and_Treatment. It was so methodical and thoughtful given how little we knew. I wonder how we regressed from that to how the pandemic evolved eventually. I wonder what we could do in the future to avoid the same mistake.
• When the pandemic begun, in April, I estimated to my mother that the worst-case scenario is that this disease might kill 1 in 100 people in countries like India. Based on personal experiences and knowledge (and how much India likely underreported deaths), this number was not very far off from reality. 1 in 100 people.

Long-term physical issues of Covid still taunt many of the people I know and care about; it's clear that this disease has changed the fundamental rates of most common causes of deaths in humans. We can only wait and see what this means in the long-term.

Children around the world have collectively and unanimously been put through the most unprecedented break in normalcy since World War II (even WWII likely did not affect the world in its entirety this much). It will be fascinating to see how this generation grows up and what effect this experience has on their adult lives and the decisions they make for humanity.

I hope someone more qualified can write a better summary than this, and if they do, I’ll happily link them here. Or change the statements above as and when there emerged clear evidence warranting it. Here’s to hoping these are lessons we don’t need again anytime in the future.

Mice

Please ignore