biology as computation

If the 20th century was the century of physics, the 21st century will be the century of biology. While combustion, electricity and nuclear power defined scientific advance in the last century, the new biology of genome research - which will provide the complete genetic blueprint of a species, including the human species - will define the next.

Craig Venter & Daniel Cohen - The Century of Biology

It took 15 years for technology to catch up with this audacious vision that was articulated in 2004. Investors who followed the pioneers got severely burned by the first hype cycle, just like those who got wiped out by the dot-com bubble.

But now the real cycle is kicking in. Cost of sequencing, storing and analyzing genomes dropped dramatically. Nations are finally initiating population wide genetics studies to jump-start their local genomic research programs. Regulatory bodies are embracing the new paradigm, changing their standards, approving new gene therapies, curating large public datasets and breaking data silos. Pharmaceutical companies and new biotech startups are flocking in droves to grab a piece of the action. Terminal patients are finding new hope in precision medicine. Consumers are getting accustomed to clinical genomic diagnostics. Popular culture is picking up as well. Our imagination is being rekindled. Skepticism from the first bust is wearing off as more and more success stories pile up.

There is something much deeper going on too. It is difficult to articulate but let me give a try.

Mathematics did a tremendous job at explaining physical phenomena. It did so well that all other academic disciplines are still burning with physics envy. As the dust settled and our understanding of physics got increasingly more abstract, we realized something more, something that is downright crazy: Physics seems to be just mathematics and nothing else. (This merits further elaboration of course, but I will refrain from doing so.)

What about biology? Mathematics could not even scratch its surface. Computer science on the other hand proved to be wondrously useful, especially after our data storage and analytics capabilities passed a certain threshold.

Although currently a gigantic subject on its own, at its foundations, computer science is nothing but constructive mathematics with space and time constraints. Note that one can not even formulate a well-defined notion of complexity without such constraints. For physics, complexity is a bug, not a feature, but for biology it is the most fundamental feature. Hence it is not a surprise that mathematics is so useless at explaining biological phenomena. 

The fact that analogies between computer science and biology are piling up gives me the feeling that we will soon (within this century) realize that biology and computer science are really just the same subject.

This may sound outrageous today but that is primarily because computer science is still such a young subject. Just like physics converged to mathematics overtime, computer science will converge to biology. (Younger subject converges to the older subject. That is why you should always pay attention when a master of the older subject has something to say about the younger converging subject.)

The breakthrough moment will happen when computer scientists become capable of exploiting the physicality of information itself, just like biology does. After all hardware is just frozen software and information itself is something physical that can change shape and exhibit structural functionalities. Today we freeze because we do not have any other means of control. In the future, we will learn how to exert geometric control and thereby push evolution into a new phase that exhibits even more teleological tendencies.

A visualization of the AlexNet deep neural network by Graphcore

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If physics is mathematics and biology is computer science, what is chemistry then?

Chemistry seems to be an ugly chimera. It can be thought of as the study of either complicated physical states or failed biological states. (Hat tip to Deniz Kural for the latter suggestion.) In other words, it is the collection of all the degenerate in-between phenomena. Perhaps this is the reason why it does not offer any deep insights, while physics and biology are philosophically so rich.

resilience vs sensitivity

Justice embedded in your genes. The further you fall the more potential energy you can mobilize to climb back.

In 2010, a team of researchers launched a research study, called the Strong African American Families project, or SAAF, in an impoverished rural belt in Georgia. It is a startlingly bleak place overrun by delinquency, alcoholism, violence, mental illness, and drug use. Abandoned clapboard houses with broken windows dot the landscape; crime abounds; vacant parking lots are strewn with hypodermic needles. Half the adults lack a high school education, and nearly half the families have single mothers.

Six hundred African-American families with early-adolescent children were recruited for the study. The families were randomly assigned to two groups. In one group, the children and their parents received seven weeks intensive education, counseling, emotional support, and structured social interventions focused on preventing alcoholism, binge behaviors, violence, impulsiveness, and drug use. In the control group, the families received minimal interventions. Children in the intervention group and in the control group had the 5HTTLPR gene sequenced.

The first result of this randomized trial was predictable from prior studies: in the control group, children with the short variant - i.e. the high risk" form of the gene - were twice as likely to veer toward high-risk behaviors, including binge drinking, drug use, and sexual promiscuity as adolescents, confirming earlier studies that had suggested an increased risk within this genetic subgroup. The second result was more provocative: These very children were also the most likely to respond to the social interventions. In the intervention group, children with the high-risk allele were most strongly and rapidly "normalized" - i.e. the most drastically affected subjects were also the best responders. In a parallel study, orphaned infants with the short variant of 5HTTLPR appeared more impulsive and socially disturbed than their long-variant counterparts at baseline - but were also the most likely to benefit from placement in a more nurturing foster-care environment.

In both cases, it seems, the short variant encodes a hyperactive "stress sensor" for psychic susceptibility, but also a sensor most likely to respond to an intervention that targets the susceptibility. The most brittle or fragile forms of psyche are the most likely to be distorted by trauma-inducing environments—but are also the most likely to be restored by targeted interventions. It is as if resilience itself has a genetic core: Some humans are born resilient (but are less responsive to interventions), while others are born sensitive (but more likely to respond to changes in their environments).

The Gene - Siddhartha Mukherjee (Pages 459-460)

Injustice has environmental origins. Under equal conditions, both sensitive and resilient types should on average experience the same elevation.

suboptimality of monogamy

Biological systems are replete with barbell strategies. Take the following mating approach, which we call the 90 percent accountant, 10 percent rock star. Females in the animal kingdom, in some monogamous species (which include humans), tend to marry the equivalent of the accountant, or, even more colorless, the economist, someone stable who can provide, and once in a while they cheat with the aggressive alpha, the rock star, as part of a dual strategy. They limit their downside while using extrapair copulation to get the genetic upside, or some great fun, or both. Even the timing of the cheating seems nonrandom, as it corresponds to periods of high likelihood of pregnancy. We see evidence of such a strategy with the so-called monogamous birds: they enjoy cheating, with more than a tenth of the broods coming from males other than the putative father. The phenomenon is real, but the theories around it vary. Evolutionary theorists claim that females want both economic-social stability and good genes for their children. Both cannot be always obtained from someone in the middle with all these virtues (though good gene providers, those alpha males aren't likely to be stable, and vice versa). Why not have the pie and eat it too? Stable life and good genes.

Antifragile - Nassim Nicholas Taleb (Pages 162-163)

True monogamy is evolutionarily suboptimal. This will be painfully apparent in near future when everyone's genome will be sequenced at birth.

Note that the most optimal strategy highlighted by Taleb is accessible only in an incomplete-information environment. If everyone could see the genetic landscape, the strategy would fail because

• alpha fathers would not be open to the idea of their children being reared by others and
• non-alpha fathers would not want to spend their resources to rear others' children.

necessity of dying

Cancer is agelessness achieved at cellular level. We want to defeat it in order to achieve agelessness at bodily level.

How ironic.

What we do not see is that agelessness achieved at bodily level will in turn destroy agelessness we achieved at societal level by destroying the most important circuit breaker of societal positive feedback loops. Without death, we will have power concentrations of catastrophic magnitudes. Intergenerational transmission mechanisms will become pointless as the need to hand over anything to younger generations disappears. We will become like cancer cells, endangering the survival of our very society by refusing to die.

How tragic.

philosophy of dockerization

To persist you can either be inflexible and freeze your local environment into constancy or be flexible and continuously morph along with your environment. Former is the direction digital entities pursue and latter is the direction biological entities pursue. (Either way, at the extreme end, complete correlation with the environment results in complete diffusion of identity.)

Non-adaptive entities like pieces of code can only survive via dockerization. Adaptive entities persist in a weaker sense but they can do so by themselves. Non-adaptive entities on the other hand can only persist with the help of adaptive entities whom they need for the execution of the dockerization processes.

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Going back to our childhood neighbourhoods and seeing them completely changed is so sad and destabilising. I wish we could dockerize our moments so that we can visit them later.

Dockerization in this sense is the ultimate form of nostalgia.

genericity and artificiality

Now that we proved faces are generic with respect to genes, life feels even more like a computer game. 

Left Real, Right Predicted

Finite variations within genomes explain most of the differences between our faces. The rest of the differences seem to be due to wear and tear.

There is a correlation between the extent of observable variation and the feeling of naturalness. An object feels natural if the variation among the relevant population looks infinite. Otherwise it feels artificial.

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Despite all the apparent complexity and drama, variations among personalities too seem to be quiet contained. Big Five personality traits explain most of the variance. The output structure of IBM Watson's semantic take on personality analysis does not look too rich neither.

Watson Personality Insights takes your social media feed as an input and spits out a graph like above as an output.

Of course, personality is a relational concept. How one behaves changes with respect to who one is interacting with. But focusing solely on one's relationship with a common reference point should be good enough for comparative purposes.

This approach is similar to extracting a variant from a genome by comparing it to a reference genome constructed out of the set of all genomes of the relevant population. Everyone's social media feed reveals how they interact with "the public", which acts sort of like a "reference personality", an average entity representing one's social network.

On a related note, dialogues with humanoid robots feel unnatural today partly due to the non-relational aspects of their personalities. Someone behaving in exactly the same manner regardless of context is deemed to be abnormal.

Consistency shows character, but too much of it is inhuman, as so eloquently pointed out by Walt Whitman in his famous quote: "Do I contradict myself? Very well. Then I contradict myself. I am large. I contain multitudes."

hierarchy and testosterone

Hierarchies select for testosterone heavy traits. In a world where only the high testosterone people can rise to the top, decisions will be testosterone driven. Hence, if you want to make the world a little less aggressive place, you should start by making the internal structure of the decision making entities less hierarchical. But how do you proceed?

• Keeping the size of the entities small is one option. But competition and scale effects favour consolidation. Hence this will not work out in any sensible economic regime.
• Trying out non-hierarchical organisational structures like holacracy is another option. But these flat fantasies never last too long. None of the large entities can even hope to give them a try.
• Waiting for artificial intelligence to mature seems to be the most feasible option at the moment. AI will dramatically decrease the need for human decision making so that even the largest entities can be run like a small entity.

neocortices vs genes

A spider will spin a web, a caterpillar will create her own cocoon, and a beaver will build a dam, even if no contemporary ever showed them how to accomplish these complex tasks... The evolution of animal behaviour does constitute a learning process, but it is learning by the species, not by the individual, and the fruits of this learning process are encoded in DNA. To appreciate the significance of the evolution of the neocortex, consider that it greatly sped up the process of learning from thousands of years to months (or less)...

There are on the order of a quadrillion connections in the neocortex, yet only about 25 million bytes of design information in the genome (after lossless compression), so the connections themselves cannot possibly be predetermined genetically... The connections between modules are created on the whole from experience (nurture rather than nature).

- How to Create a Mind (Raymond Kurzweil)

Development of neocortex was in some sense inevitable. As evolution created more complexity over time, the ecosystem became harder to navigate and its participants needed a more versatile and quicker way of absorbing greater quantities of information.

Genes are slow and one dimensional, while the brand new neocortices are lightening fast and three dimensional. The downside is that what is learned through a neocortex has much lower chances of being faithfully transferred to the next generation. Cultural mechanisms are limited and nowhere near as accurate as the biological ones. 

Note that this intergenerational transferability issue is what is responsible for the much deeper computational complexity of genetic learning. While we could basically reverse-engineer the neocortex through hierarchical hidden Markov models, we still can not even define what it means to be a single gene. Usually later technologies are harder to reverse-engineer, but it has not been the case here since neocortices and genes do not replace one another but are built on top of one another.

Keep in mind that Kurzweil is probably significantly underestimating the genomic information density:

1. Firstly, he does not take into account context dependency. Same code fragments can assume entirely different meanings in different contexts. (This is part of the reason why we still can not define what it means to be a single gene.) In other words, some of the information is sourced from the environment.

2. Secondly, the extremely complex relationship between the code and the environment has a sequentially nested character. Decoding alters the environment and this change in the environment sets off a new chain reaction of decoding and so on. In other words, the code works on itself through the environment. This loopiness implies that the apparent one dimensionality is deceptive. Once we factor in the time dimension, genome too looks like a connectome. (Nodes are the set of all subsets of the genome.) In fact, most of the complexity comes from the network of interactions, not the nodes. (Wheat has nearly 100K genes while we have 20-25K genes. Guess who is more complex.)

maximisation, averaging and beauty

We mistakenly think of beauty as an edge case resulting from the maximisation of some complex parameters. This misconception has linguistic origins. (We say "very beautiful" and "very" implies a maximisation of some sort.) Beauty emerges not from a maximisation process but from an averaging one. That is why as more faces get pasted together using image editing tools, the resulting face looks more beautiful. 

Our biological craving for normality has a sound basis since normality often implies healthiness. But when everyone craves for normality, the genetic pool quickly becomes a mono culture and this creates a vulnerability against new health threats. Hence there is a concurrent biological need for cross cultural genetic marriages as well. That is why the sweat of genetically furthest away people smells the best in blindfolded tests.

Combining the previous two observations, we conclude that what people crave for the most is the average of the furthest away genetic pool. In other words, beauty involves both a low-level averaging process and a high-level maximisation process.

asynchronous harem instinct

There is no doubt that we are a polygynous species.

There is considerably more variation when it comes to mitochondrial DNA, which is inherited only from mothers, than in Y chromosome DNA, bestowed upon subsequent generations exclusively by fathers. In other words, over the evolutionary history of Homo sapiens, a relatively small number of men produced children with a relatively large number of women. As a species, we have had a greater variety of mothers than of fathers. 

David P Barash - Is God a Silverback?

Of course it is extremely barbarian to voice this fact in our modern society. We are supposed to get married to a single person and stay married to that person until death does us apart.

Despite being suppressed, the harem instinct is nevertheless alive with us. But it manifests itself in an asynchronous form via a proliferation of step brothers and sisters from successive marriages.