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.

a visual affair

We vastly overvalue visual input over other sources of sensual inputs since most of our bandwidth is devoted to vision:

Source: David McCandless - The Beauty of Data Visualization (The small white corner represents the total bandwidth that we can actually be aware of.)

This bias infiltrates both aesthetics and science:

• The set of people you find beautiful will change drastically if you lose your eyesight. (Get a full body massage and you will see what I mean.)

• We explain auditory phenomenon in terms of mathematical metaphors that burgeoned out of visual inputs. There are no mathematical metaphors with auditory origin, and therefore no scientific explanations of visual phenomenon in terms of auditory expressions. Rationality is a strictly visual affair. In fact, the word "idea" has etymological roots going back to the Greek word "Edeo" - "to see". (No wonder why deep neural networks mimicking the structure of our visual system has become so successful in machine learning challenges.)

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.

success vs failure

Success is defined as the negation of failure. (Until something fails for a specific reason, it is considered as successful.) This negational definition makes it very hard to understand.

There is basically only one generalizable aspect of success, namely its nonlinear nature with respect to time: The longer the success period, the lower the probability of near-future failure.

It is funny how successful people go on stage and talk about their unimaginably poor grasp of their own success stories while failed people are not given a chance to speak at all. Success is one of those things that can not be spoken about. It can only be shown.

Best success stories are concatenations of "How I Almost Failed" stories. Others consist of boring generalizations. After all, as Tolstoy said, happy families are all alike while each unhappy family is unhappy in its own way.

stability and inflation

What happens if a self-organized system cannot grow? Is growth arrest a source of aging and death for networks? Is growth arrest a serious form of stress which leads to a series of topological phase transitions of the network, resulting finally in the disintegration of the net and death? Are we sentenced to grow in running away from our own death?

- Peter Csermely - Weak Links (Page 99)

Zero growth is an obviously unstable state, but non-zero growth is not necessarily healthy neither. Economic, physical and psychological systems thrive on small and positive inflationary coefficients.

• Negative interest rates lead to deflationary dynamics that bring trade to a halt. Everyone delays their purchasing decisions and waits for prices to fall even further. Central bank sits still as well since it does not have any instruments for lowering negative interest rates even further. High interest rates on the other hand are also destabilising. Inflation gets out of control and cost of capital concerns cause companies to stop investing.

• A deflating universe collapses to a singularity in a run-away fashion. Too much inflation on the other hand pulls space-time apart so quickly that matter gets too dispersed and planets (and therefore life-forms) can no longer emerge.

• A deflating ego leads to depression. An overly optimistic view of oneself on the other hand leads to delusion. You need to fake it until you make it but also not lose touch with the reality by maintaining what psychologists call an illusion of objectivity.

on a new type of free education

"Free until you get a job" model is spreading among the fringes of the education world. (e.g. Lambda School, Make School) This unsustainably bold model works only because it sits in a very niche domain that is at the intersection of an insane student demand and an insane industrial demand.

• When there is so much student demand, you can be so selective that educating the incoming students to industrial standards becomes a trivial exercise. Even Harvard does this trick. In fact, any school that becomes good enough to attract such a student demand eventually turns into a selection-certification mechanism. (Harvard does not even optimize for university success. It selects students who will be successful after graduation and bolster its brand even further.)
• When there is so much industrial demand for the sort of talent you produce, then the risk of non-employment decreases substantially and you can charge the companies themselves rather than the students.

thoughts on shopping systems

A system with one seller and many buyers is called a shop (or an auction if only one good is being sold). When many shops are brought together, the resulting system is called an aggregator (or an auction house). If sellers can become buyers too, then it becomes a marketplace.

If seller side is closed to new entrants (which is always the case in the physical world), then what you have is something like a shopping mall. (Openness creates discoverability problems for sellers who are always willing to pay a rent for compensating the costs of maintaining a closure.)

If buyer side is closed to new entrants, then what you have is something like a shopping club. (Sellers will be willing to offer discounts to have access to such closed-off demand sources.) Shopping clubs collapse if the number of sellers is increased over time and sellers are essentially left competing as in an open system. This sooner or later happens due to competition among shopping clubs who feel pressurized to hunt for more customers and flex their closures. Of course, the irony is that when a shopping club is truly successful and every buyer and seller is in it, then it becomes the whole economy and paying a cut to the club becomes pointless for both buyers and sellers. 

Groupon tried to circumvent this fate by concentrating the demand and spacing sellers across time in return for a deep discount from each seller. It tried to achieve the paradoxical goal of having seller variety without seller competition. Since Groupon buyers moved from deal to deal and had very little loyalty, the time dimension got behaviorally collapsed and sellers again ended up competing with each other.

Groupon could eventually be brought down to its knees (by the sellers who understood what was going on) because it did not appeal to all potential buyers. (A lot of people want to be able choose from a wide variety of options rather than being dictated to a few randomly fluctuating options.) In other words, sellers had something to fall back on.

Amazon on the other hand can only be brought down by regulators because it appeals to all potential buyers. Sellers have nothing to fall back on. (Amazon does not demand a discount from sellers but exposes them to intense competition, which at the end of the day amounts to a not-as-deep-but-a-more-permanent form of discount.)

Some further thoughts:

• Only oligopolistic markets will be able to resist Amazon which started off by killing the competitive bookstore market. By becoming literally the only bookstore in town, Amazon now faces a strong resistance from a coordinating set of publishers from whom it now wants to buy directly. It can either buy its way up the supply chain or become a publisher itself like Netflix did. Former strategy will be expensive since publishers selling their businesses will be asking for very high premiums for defecting and will make Amazon pay the present value of all their future fat profit margins. Latter strategy is tough because of the same reason why Spotify will eventually fail: Creating a music star (similarly a bestselling author) is a much more complicated process then creating a hit movie. (Spotify’s profit margin is tiny compared to that of music producers and it does not seem to scale neither.) Talent discovery is stochastic and talent nurturing is difficult, and neither scales well. (Also there is a lot of consumption of old songs and books - which is not true for movies. So the incumbent producers with deep archives have a competitive advantage.)
• It is easier to sustain a shopping club in a physical environment where one can maintain a locally acceptable level of competition among the club-member sellers by sampling across all shopping malls. (In a virtual environment, there are no distances and competition is always a click away.) That is why shopping clubs usually end up housing only non-virtualizable experience goods like dinners in fancy restaurants etc.
• In a physical marketplace, buyers can not hide. A carpet seller in a bazaar can grab you by the arm and drag you to his store. In a virtual marketplace, on the other hand, all he can do is to harass you with the cooperation of the marketplace itself by using the allowed advertisement mechanisms. So, in some sense, you forfeit your right to be protected from harassment to the marketplace in return for the promise to build some norms and predictability.

risk, luck and naiveness

If risk is what happens when you make good decisions but end up with a bad outcome, luck is what happens when you make bad or mediocre decisions but end up with a great outcome. They both happen because the world is too complex to allow 100% of your actions dictate 100% of your outcomes. They are mirrored cousins, driven by the same thing: You are one person in a 7 billion player game, and the accidental impact of other people’s actions can be more consequential than your own... Risk doesn’t care about how much effort you put into something, and neither does luck. Both just show up, unannounced, eager to humble you. The only difference is that risk humbles you as soon as it arrives, while luck humbles you down the road, once it vanishes, leaving you with only the memories you shared together.

Morgan Housel - Ironies of Luck

Let us define people who believe that all good outcomes come from good decisions and all bad outcomes come from bad decisions as naive. 

Naive and lucky people (people who are lucky but do not know that they are lucky) systematically overestimate the upside potential of their good decisions because they can not see that a portion of their good outcomes are coming from their bad decisions. Consequently they feel like they can take bigger risks. At some point their luckiness can no longer compensate for their increased risk taking and their returns collapse back to a state of normalcy where they either make big gains or big losses.

Naive and risk taking people (people who take risk but do not know that they are taking a risk) systematically overestimate the downside potential of their bad decisions because they can not see that a portion of their bad outcomes are coming from their good decisions. Consequently they feel unlucky. They scale back their risk taking behavior and their returns collapse back to a state of normalcy where they either make small gains or small losses.

So you need to know thyself and shed your naiveness away in order to sustain the positive returns due to luck or risk. (Remember that each person tends to be naive in a different way.)

belief, trust and finance

Fundamentals of finance are taught wrongly in schools.

• We do not trade future cash flows, we trade beliefs about future cash flows. (See the old blog post misconception of wealth) When beliefs are completely aligned and future cash flows assume an objective quality, it is no longer possible to make a profit and financial interest disappears.
• We do not operate in legal frameworks, we operate in trust frameworks. Only when the shit hits the fan does the legal framework surface, and when it does, you are no longer in the domain of finance.

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.