## Hiding behind chaos and error in the double pendulum

If you want a visual intuition for just how unpredictable chaotic dynamics can be then the go-to toy model is the double pendulum. There are lots of great simulations (and some physical implementations) of the double pendulum online. Recently, /u/abraxasknister posted such a simulation on the /r/physics subreddit and quickly attracted a lot of attention.

In their simulation, /u/abraxasknister has a fixed center (block dot) that the first mass (red dot) is attached to (by an invisible rigid massless bar). The second mass (blue dot) is then attached to the first mass (also by an invisible rigid massless bar). They then release these two masses from rest at some initial height and watch what happens.

The resulting dynamics are at right.

It is certainly unpredictable and complicated. Chaotic? Most importantly, it is obviously wrong.

But because the double pendulum is a famous chaotic system, some people did not want to acknowledge that there is an obvious mistake. They wanted to hide behind chaos: they claimed that for a complex system, we cannot possibly have intuitions about how the system should behave.

In this post, I want to discuss the error of hiding behind chaos, and how the distinction between microdynamics and global properties lets us catch /u/abraxasknister’s mistake.
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## Introduction to Algorithmic Biology: Evolution as Algorithm

As Aaron Roth wrote on Twitter — and as I bet with my career: “Rigorously understanding evolution as a computational process will be one of the most important problems in theoretical biology in the next century. The basics of evolution are many students’ first exposure to “computational thinking” — but we need to finish the thought!”

Last week, I tried to continue this thought for Oxford students at a joint meeting of the Computational Society and Biological Society. On May 22, I gave a talk on algorithmic biology. I want to use this post to share my (shortened) slides as a pdf file and give a brief overview of the talk.

If you didn’t get a chance to attend, maybe the title and abstract will get you reading further:

Algorithmic Biology: Evolution is an algorithm; let us analyze it like one.

Evolutionary biology and theoretical computer science are fundamentally interconnected. In the work of Charles Darwin and Alfred Russel Wallace, we can see the emergence of concepts that theoretical computer scientists would later hold as central to their discipline. Ideas like asymptotic analysis, the role of algorithms in nature, distributed computation, and analogy from man-made to natural control processes. By recognizing evolution as an algorithm, we can continue to apply the mathematical tools of computer science to solve biological puzzles – to build an algorithmic biology.

One of these puzzles is open-ended evolution: why do populations continue to adapt instead of getting stuck at local fitness optima? Or alternatively: what constraint prevents evolution from finding a local fitness peak? Many solutions have been proposed to this puzzle, with most being proximal – i.e. depending on the details of the particular population structure. But computational complexity provides an ultimate constraint on evolution. I will discuss this constraint, and the positive aspects of the resultant perpetual maladaptive disequilibrium. In particular, I will explain how we can use this to understand both on-going long-term evolution experiments in bacteria; and the evolution of costly learning and cooperation in populations of complex organisms like humans.

Unsurprisingly, I’ve writen about all these topics already on TheEGG, and so my overview of the talk will involve a lot of links back to previous posts. In this way. this can serve as an analytic linkdex on algorithmic biology.
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## British agricultural revolution gave us evolution by natural selection

This Wednesday, I gave a talk on algorithmic biology to the Oxford Computing Society. One of my goals was to show how seemingly technology oriented disciplines (such as computer science) can produce foundational theoretical, philosophical and scientific insights. So I started the talk with the relationship between domestication and natural selection. Something that I’ve briefly discussed on TheEGG in the past.

Today we might discuss artificial selection or domestication (or even evolutionary oncology) as applying the principles of natural selection to achieve human goals. This is only because we now take Darwin’s work as given. At the time that he was writing, however, Darwin actually had to make his argument in the other direction. Darwin’s argument proceeds from looking at the selection algorithms used by humans and then abstracting it to focus only on the algorithm and not the agent carrying out the algorithm. Having made this abstraction, he can implement the breeder by the distributed struggle for existence and thus get natural selection.

The inspiration is clearly from the technological to the theoretical. But there is a problem with my story.

Domestication of plants and animals in ancient. Old enough that we have cancers that arose in our domesticated helpers 11,000 years ago and persist to this day. Domestication in general — the fruit of the first agricultural revolution — can hardly qualify as a new technology in Darwin’s day. It would have been just as known to Aristotle, and yet he thought species were eternal.

Why wasn’t Aristotle or any other ancient philosopher inspired by the agriculture and animal husbandry of their day to arrive at the same theory as Darwin?

The ancients didn’t arrive at the same view because it wasn’t the domestication of the first agricultural revolution that inspired Darwin. It was something much more contemporary to him. Darwin was inspired by the British agricultural revolution of the 18th and early 19th century.

In this post, I want to sketch this connection between the technological development of the Georgian era and the theoretical breakthroughs in natural science in the subsequent Victorian era. As before, I’ll focus on evolution and algorithm.

## Four stages in the relationship of computer science to other fields

This weekend, Oliver Schneider — an old high-school friend — is visiting me in the UK. He is a computer scientist working on human-computer interaction and was recently appointed as an assistant professor at the Department of Management Sciences, University of Waterloo. Back in high-school, Oliver and I would occasionally sneak out of class and head to the University of Saskatchewan to play counter strike in the campus internet cafe. Now, Oliver builds haptic interfaces that can represent virtually worlds physically so vividly that a blind person can now play a first-person shooter like counter strike. Take a look:

Now, dear reader, can you draw a connecting link between this and the algorithmic biology that I typically blog about on TheEGG?

I would not be able to find such a link. And that is what makes computer science so wonderful. It is an extremely broad discipline that encompasses many areas. I might be reading a paper on evolutionary biology or fixed-point theorems, while Oliver reads a paper on i/o-psychology or how to cut 150 micron-thick glass. Yet we still bring a computational flavour to the fields that we interface with.

A few years ago, Karp’s (2011; Xu & Tu, 2011) wrote a nice piece about the myriad ways in which computer science can interact with other disciplines. He was coming at it from a theorist’s perspective — that is compatible with TheEGG but maybe not as much with Oliver’s work — and the bias shows. But I think that the stages he identified in the relationship between computer science and others fields is still enlightening.

In this post, I want to share how Xu & Tu (2011) summarize Karp’s (2011) four phases of the relationship between computer science and other fields: (1) numerical analysis, (2) computational science, (3) e-Science, and the (4) algorithmic lens. I’ll try to motivate and prototype these stages with some of my own examples.
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## On Frankfurt’s Truth and Bullshit

In 2015 and 2016, as part of my new year reflections on the year prior, I wrote a post about the ‘year in books’. The first was about philosophy, psychology and political economy and it was unreasonably long and sprawling as post. The second time, I decided to divide into several posts, but only wrote the first one on cancer: Neanderthals to the National Cancer Act to now. In this post, I want to return two of the books that were supposed to be in the second post for that year: Harry G. Frankfurt’s On Bullshit and On Truth.

Reading these two books in 2015 might have been an unfortunate preminission for the post-2016 world. And I wonder if a lot of people have picked up Frankfurt’s essays since. But with a shortage of thoughts for this week, I thought it’s better late than never to share my impressions.

In this post I want to briefly summarize my reading of Frankfurt’s position. And then I’ll focus on a particular shortcoming: I don’t think Frankfurt focuses enough on how and what for Truth is used in practice. From the perspective of their relationship to investigation and inquiry, Truth and Bullshit start to seem much less distinct than Frankfurt makes them. And both start to look like the negative force — although in the case of Truth: sometimes a necessary negative.
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## Coarse-graining vs abstraction and building theory without a grounding

Back in September 2017, Sandy Anderson was tweeting about the mathematical oncology revolution. To which Noel Aherne replied with a thorny observation that “we have been curing cancers for decades with radiation without a full understanding of all the mechanisms”.

This lead to a wide-ranging discussion and clarification of what is meant by terms like mechanism. I had meant to blog about these conversations when they were happening, but the post fell through the cracks and into the long to-write list.

This week, to continue celebrating Rockne et al.’s 2019 Mathematical Oncology Roadmap, I want to revisit this thread.

And not just in cancer. Although my starting example will focus on VEGF and cancer.

I want to focus on a particular point that came up in my discussion with Paul Macklin: what is the difference between coarse-graining and abstraction? In the process, I will argue that if we want to build mechanistic models, we should aim not after explaining new unknown effects but rather focus on effects where we already have great predictive power from simple effective models.

Since Paul and I often have useful disagreements on twitter, hopefully writing about it on TheEGG will also prove useful.

## Colour, psychophysics, and the scientific vs. manifest image of reality

Recently on TheEGG, I’ve been writing a lot about the differences between effective (or phenomenological) and reductive theories. Usually, I’ve confined this writing to evolutionary biology; especially the tension between effective and reductive theories in the biology of microscopic systems. For why this matters to evolutionary game theory, see Kaznatcheev (2017, 2018).

But I don’t think that microscopic systems are the funnest place to see this interplay. The funnest place to see this is in psychology.

In the context of psychology, you can add an extra philosophical twist. Instead of differentiating between reductive and effective theories; a more drastic difference can be drawn between the scientific and manifest image of reality.

In this post, I want to briefly talk about how our modern theories of colour vision developed. This is a nice example of good effective theory leading before any reductive basis. And with that background in mind, I want to ask the question: are colours real? Maybe this will let me connect to some of my old work on interface theories of perception (see Kaznatcheev, Montrey, and Shultz, 2014).

## Constant-sum games as a way from non-cell autonomous processes to constant tumour growth rate

A lot of thinking in cancer biology seems to be focused on cell-autonomous processes. This is the (overly) reductive view that key properties of cells, such as fitness, are intrinsic to the cells themselves and not a function of their interaction with other cells in the tumour. As far as starting points go, this is reasonable. But in many cases, we can start to go beyond this cell-autonomous starting point and consider non-cell-autonomous processes. This is when the key properties of a cell are not a function of just that cell but also its interaction partners. As an evolutionary game theorist, I am clearly partial to this view.

Recently, I was reading yet another preprint that has observed non-cell autonomous fitness in tumours. In this case, Johnson et al. (2019) spotted the Allee effect in the growth kinetics of cancer cells even at extremely low densities (seeding in vitro at <200 cells in a 1 mm^3 well). This is an interesting paper, and although not explicitly game-theoretic in its approach, I think it is worth reading for evolutionary game theorists.

Johnson et al.'s (2019) approach is not explicitly game-theoretic because they consider their in vitro populations as a monomorphic clonal line, and thus don't model interactions between types. Instead, they attribute non-cell autonomous processes to density dependence of the single type on itself. In this setting, they reasonably define the cell-autonomous null-model as constant exponential growth, i.e. $\dot{N}_T = w_TN_T$ for some constant fitness $w_T$ and total tumour size $N_T$.

It might also be tempting to use the same model to capture cell-autonomous growth in game-theoretic models. But this would be mistaken. For this is only effectively cell-autonomous at the level of the whole tumour, but could hide non-cell-autonomous fitness at the level of the different types that make up the tumour. This apparent cell-autonomous total growth will happen whenever the type interactions are described by constant-sum games.

Given the importance of constant-sum games (more famously known as zero-sum games) to the classical game theory literature, I thought that I would write a quick introductory post about this correspondence between non-cell autonomous constant-sum games and effectively cell-autonomous growth at the level of the whole tumour.

## Local maxima and the fallacy of jumping to fixed-points

An economist and a computer scientist are walking through the University of Chicago campus discussing the efficient markets hypothesis. The computer scientist spots something on the pavement and exclaims: “look at that $20 on the ground — seems we’ll be getting a free lunch today!” The economist turns to her without looking down and replies: “Don’t be silly, that’s impossible. If there was a$20 bill there then it would have been picked up already.”

This is the fallacy of jumping to fixed-points.

In this post I want to discuss both the importance and power of local maxima, and the dangers of simply assuming that our system is at a local maximum.

So before we dismiss the economist’s remark with laughter, let’s look at a more convincing discussion of local maxima that falls prey to the same fallacy. I’ll pick on one of my favourite YouTubers, THUNK:

In his video, THUNK discusses a wide range of local maxima and contrasts them with the intended global maximum (or more desired local maxima). He first considers a Roomba vacuum cleaner that is trying to maximize the area that it cleans but gets stuck in the local maximum of his chair’s legs. And then he goes on to discuss similar cases in physics, chemisty, evolution, psychology, and culture.

It is a wonderful set of examples and a nice illustration of the power of fixed-points.

But given that I write so much about algorithmic biology, let’s focus on his discussion of evolution. THUNK describes evolution as follows:

Evolution is a sort of hill-climbing algorithm. One that has identified local maxima of survival and replication.

This is a common characterization of evolution. And it seems much less silly than the economist passing up $20. But it is still an example of the fallacy of jumping to fixed-points. My goal in this post is to convince you that THUNK describing evolution and the economist passing up$20 are actually using the same kind of argument. Sometimes this is a very useful argument, but sometimes it is just a starting point that without further elaboration becomes a fallacy.

## Quick introduction: the algorithmic lens

Computers are a ubiquitous tool in modern research. We use them for everything from running simulation experiments and controlling physical experiments to analyzing and visualizing data. For almost any field ‘X’ there is probably a subfield of ‘computational X’ that uses and refines these computational tools to further research in X. This is very important work and I think it should be an integral part of all modern research.

But this is not the algorithmic lens.

In this post, I will try to give a very brief description (or maybe just a set of pointers) for the algorithmic lens. And of what we should imagine when we see an ‘algorithmic X’ subfield of some field X.