…You can have the robust, conscious experience of having intended an action even if this wasn’t the case. By directly stimulating the brain, we can trigger not only the execution of bodily movement but also the conscious experience of having the urge to perform that movement. We can experimentally induce the conscious experience of will.

Here’s an example. Stéphane Kremer and his collegues at the University Hospital of Strasbourg stimulated a specific brain region (the ventral bank of the anterior cingulate sulcus) in a female patient with medically intractable epilectic seizures, in order to locate the epileptogenic zone before performing surgery. In this case, the stimulation caused rapid eye movements scanning both sides of the visual field. The patient began to search for the nearest object she could grasp, and the arm that was opposite the stimulated side -her left arm- began to wander to the right. Sher reported a strong “urge to grasp”, which she was unable to control. As soon as she saw a potential target object, her left hand moved toward it and seized it. On the level of her conscious experience, the irrepressible urge to grasp the object started and ended with the stimulation of her brain. This much is clear: Whatever else the conscious experience of will may be, it seems to be something that can be turned on and off with the help of a small electrical current from an electrode in the brain

Thomas Metzinger, The Ego Tunne, 2009.

When he was very old and dying in his bed, many fellow citizens came to him to say goodbye and, perhaps, get the last sparkles of his wisdom. Despite his pain and illness and despite his terrible condition, Ma Guang-Zhong was quiet, smiling and cheerful.

Just before he died, he was asked the secret formula of happiness. His last words were: “The formula of happiness? It’s not a secret: C₂₁H₂₃NO₅.”

Folding is not permanent!

Biomolecules are highly dynamic. Let’s not think about the folding as a permanent phenomena. It trivial to notice that particular  physico-chemical conditions or enzymes may alter (or destroy) the protein shape, for example, urea (H2N-CO-NH2) or heat denature proteins.

The same protein may have different spatial configuration and be activated like a on/off (or multistate) switch. For example, a certain protein may be utilized literally as a gate to let some specific substance get in or out a cell. Furthermore, a pretty high number of proteins (estimated  36 – 63% in eukaryotes; 7 – 33% in prokaryotes and archaebacteria [ref]) is intrinsically disordered. This means those proteins do not have stable three-dimensional conformation.

In fact, as reported on “The brain that changes itself” (Norman Doidge, 2007):

For millenia most marriages were arranged by parents for practical reasons. Certainly, there are unforgettable stories of romantic love linked to marriage in the Bible, as in the Song of Songs, and linked to disaster in medieval troubadour poetry and, later, in Shakespeare. But romantic love began to gain social approval in the aristocracies and courts of Europe only in the twelfth century- originally between an unmarried man and a married woman, either adulterous or unconsummated, usually ending badly. Only with the spread of democratic ideals of individualism did the idea that lovers pught to be able to choose spouses for themselves take fimer hold and gradually begin to seem completely natural and inalienable.

Bouns: Wilbur Sargunaraj famous hit Love Marriage. :D

Genetic Determinism is a theory stating that the ordered mechanisms of cell growth and behavior are commanded by DNA in a predictable (deterministic) way, even at the microscopic level. (We will see in other posts how this strict rule can be challenged, like all the other strict rules in Biology.)

Postulated differences between Biological and purely Physical systems.

There is a fundamental difference, according to Genetic Determinism, between Biology and Physics. (This postulated difference is standing on the very root of Genetic Determinism.)

In Physics, molecules and atoms have a random (unpredictable) behavior because of a number of factors, for example thermal agitation and randomness, while at the macroscopic level we can describe the systems with deterministic rules.  We can predict the general behavior of a gas mass, but not the particular trajectory of a molecule embedded in that mass. The reason of this behavioral gap rely on the huge number of involved particles. The principle is thus described as order from disorder. (But, given a sufficient computational power, could we model and predict in deterministic way the behavior of each single particle? I think yes, we can.) While this happens to physical system, and we all agree about the  fact that the order from disorder approach works, according to Genetic Determinism the biological systems present a different paradigm. The number of molecules in the biological cases is in fact too small (for example, considering a cell as the system) to be compared to the aforementioned gas mass, and in general physical systems. So Genetic Determinism says there is no order from disorder in Molecular Biology, but order from order instead.

Some history.

Determinism in Biology was present since the beginning (we can even say determinism fueled the pioneering Biology studies: let’s just think about Mendel’s model). Even Erwin Schrödinger, father of quantum physics and its stochastic nature, in his book “What is life” (1944) postulates the deterministic nature of Biology. Genetic Determinism lead to two considerations: (a) that environmental factors had little influence on cells’ fate and (b) the concept of stereospecificity.

(a) Genetic Determinism was inferred throughout last century, till the point some scientist thought the whole destiny of a living being was embedded in its DNA, including the fate of complex phenomena such as, for example, human social behavior. This approach was later dismissed because evidence points another direction. DNA is a set of instructions: it does not tell us what the cell will be in the future, but how the cell will react to stimuli. The behavior or growth of a living system depends in fact not just on the genes, but also on the stimuli (the environment).

(b) Around 1960, the concept of stereospecific self-assembly was put forward by molecular biologists [...] biological molecular interactions were said to be strictly ordered. Because of the form and electric constraints caused by their tri-dimensional structure, proteins recognize each other and interact specifically just as the pieces of a puzzle do, each protein having only one partner, or a very limited and defined number, excluding any combinatorial possibility and randomness in these interactions.

By Gnosticism we mean a number of cults loosely based on the idea that not God, but a lesser spirit called Demiurge made the material world. According to Gnosticism, human souls are trapped into mortal bodies and liberation can occur following a path of secret knowledge. Gnosticism rejects the idea of a world in which objective good (God) is fighting with objective evil (Satan).

Most [Gnostic cults] were based on a dualistic concept of good and evil as eternal and sometimes sacred spiritual forces. This dualism was more extreme than the qualified dualism of Christianity in which good and evil have been construed as existing in opposition to one another, but where the good is considered to be infinitely more powerful and is predicted to ultimately prevail. Judaism, in contrast, has presented a more monistic position on this question whereby good and evil are usually both subsumed as normal features of God’s creation, where Satan is a relatively unimportant figure and necessarily God’s adversary.

One of the prominent Gnostic themes was that the creator of the universe, sometimes called the Demiurge, was an inept, or overtly evil, spiritual being. The Demiurge arrogantly and falsely believed himself to be the god who ruled heaven and earth but was actually a spiritual entity of lower rank in comparison with the true, ultimate god of the Gnostics. The human spirit was viewed as a spark of ultimate deity trapped within the inferior and evil material body created by the Demiurge. Many Gnostics equated the Demiurge with the God of Israel, whom Christians call God, the Father. Conversely, the serpent mentioned in the Genesis (and considered by Christians to be Satan) was viewed by many Gnostics as benevolent and wise being who had come into the world to help humanity learn the desperately needed knowledge of good and evil. [...]

James Randall Noblitt and Pamela Sue Perskin, Cult and ritual abuse, 2000.

The most intriguing aspect of Gnosticism is a logical interpretation of the creation myth in the bible. God says in the bible: “…for the day that you eat from from it you will surely die”. The snake says: “On the day when you eat from the tree [...] the eyes of your mind will be opened” [1].

The Gnostics observed that Adam and Eve did not die the day they ate the forbidden fruit, but that their eyes were opened. Thus, they concluded that the serpent was correct and the God of creation was in error or had been lying. [...] Gnostics had essentially reversed what orthodox (or “straight.thinking”) Christians regarded as the holiest of beings with the one who was regarded as most evil. In some instances, from a Gnostic point of view, Christianity was Satanism, and from a Christian point of view, Gnosticism was Satanism. However, many Gnostics did consider themselves to be Christian, and although they had adverse opinions about God the Father, they were usually favorably predisposed toward Jesus, whom they considered to be (along with the serpent) a savior figure who had come to earth to convey knowledge.

James Randall Noblitt and Pamela Sue Perskin, Cult and ritual abuse, 2000.

This said, I remain a strong atheist, no matter how cool Gnostic cults beliefs may sound. Nevertheless, the Gnostic approach seems to judge the bible’s God from its action which, especially in the old testament, are not consistent with a benevolent god but with a arrogant and moody one.

[1] From the King James edition:

2:17 But of the tree of the knowledge of good and evil, thou shalt not eat of it: for in the day that thou eatest thereof thou shalt surely die.

3:4    And the serpent said unto the woman, Ye shall not surely die:

3:5    For God doth know that in the day ye eat thereof, then your eyes shall be opened, and ye shall be as gods, knowing good and evil.

Examples of log-normal distributions with formula. (no shame: I stole this picture online.)

I recently moved to a new flat.

I realized that in the last 7 years I’ve been wandering from a flat to another (usually sharing with some weirdos), and I never stayed in a house for more than a few months. Even when I was stuck in a single city, such as Hong Kong, I’ve been constantly moving to new flats in a inner-city nomadic cycle. In Hong Kong, in fact, I have been living in Yau Ma Tei (2 different flats), Prince Edward, Clearwater Bay, Sham Shui Po, North Point and Causeway Bay. I also lived in Madrid, Pavia (Italy), Voghera (Italy) and Beijing. I’m not taking into consideration my travels, but only the flats I rented for one month or more.

So I computed the duration of stays, in months, since Aug 2004 to Dec 2011:

12, 8, 5, 17, 4, 5, 2, 2, 1.5, 7, 3, 2, 1, 2, 6.5, 2.5, 1, 2.

Analysing this distribution with the Kolmogorov-Smirnoff (K-S) test, it turns out that there’s a 0.55 chance it is a log-normal one and a 0.06 probability it is Gaussian. Log-normal means that if we compute the normal logarithm of each value, the resulting distribution is Gaussian (here we are assuming normal = Gaussian). The K-S test is a non parametric test to check if some unknown distribution is similar to a Gaussian distribution. Actually, there are better, more fine-tuned methods to check the normality of a new data set, but the K-S test is a quick solution (and it works pretty well).

So let’s take my nomadism as log-normal. It has a mean 3.54 and a standard deviation of 4.24. Median = 2.75. According to Tukey definition, there is just one outlier: a odd 17-month stay back in the old days… well, if I keep this outlier out the distribution and I repeat the test, results are almost the same.

Here is a list of phenomena with a log-normal distribution:

• Salmonellosis disease latency period
• Uranium, gold, chrome, gallium (and other minerals) concentration under the Earth surface
• Air pollution in Huston, Texas.
• Content of hydroxymethylfurfurol in honey
• Average diameter of crystals in ice creams.
• Alzheimer’s disease age of onset.
• Lenght of my stays in a flat, August 2004 – Dec 2011.

And now what? Well, beside wasting my time to calculate and for writing this post, I could predict, for example, what is the probability of me moving in the next 3 months, or next year, on in 3 weeks… that’s the nice thing one can do once he has data with a well-known distribution in his hands. But I will not do it: I am nerdy, but not that nerdy. (Furthermore, I can not measure double-bind cohort studies on my own nomadic attitude, damn it.)

Protein structure is determined by folding.

Proteins are among the basic elements of carbon-based life forms. They are made of Amino Acids (AAs): a protein, in other words, is a sequence of AAs. While the AAs are assembled inside the cell, like lego bricks, the protein folds in a three-dimensional shape. AAs, in fact, are affected by chemical and physical forces thatinteract repelling or attracting each other. One of the most important force is hydrophobicity: on the one hand hydrophobic AAs are pulled away from the cell environment, which is aqueous, on the other hand hydrophilic AAs tend to be exposed. The shape a protein will have will determine a specific three-dimensional structure, and the protein will only interact with targets according to the structure, in lock-and-key fashion. In other words, sequence determines structure, and structure determines interaction.

We can analyze proteins’ structure on four levels: primary, secondary, tertiary and quaternary structure respectively.

The primary structure is simply the AA sequence composing the protein. There are 20 so-called canonical AAs that constitute the alphabet of protein sequences. For example, the human protein IRF-4 (Interferon regulatory factor 4) is composed by 451 AAs. Each AA is represented by a letter, and the first 10 AAs are:

MNLEGGGRGG…

…up to 451. That’s the primary sequence: a long string of characters.

The secondary structure is the general three-dimensional form of local segments, or modules, and it is a simplified but useful description of the protein spatial orientation. Groups of AAs are described in secondary structure as blocks with particular characteristics (i.e. the shape). Secondary structure is sometimes improperly called “2D structure”: this questionable nomenclature may induce readers to think about a two-dimensional description, while it obviously is a three-dimensional one.

The tertiary structure is a viable description of the three-dimensional protein orientation down to the atomic details, thus more precise and complex than the secondary one.

Finally, the quaternary structure is the folding description of a multi-subunit complex, made by more than one peptide.

Protein interaction targets are determined by structure in a lock and key fashion.

When we say a protein interacts with a target, for example another protein, it means that only some (usually very small) specific part of the protein are actually involved in the interaction. We can detect these protein portions. Functional blocks from the secondary structure, for example, may be utilized in this search. Finding the motif, or pattern, that triggers the interacting may be hard: because of the three-dimensional shape, in fact, some AAs that are away from each other in the sequence (primary structure, very easy to analyze) can indeed be very close, spatially, once the protein is folded (but to find them we need to analyze the tertiary structure, and this is harder).

What is unpredictable? Well, not surprisingly, it is something we can not foresee. So, is it random? In common speech, yes. But there is a slight difference: unpredictable is something we have no ability to predict yet: maybe in the future, with more knowledge, we will overcome the problem. Au contraire, a truly random phenomena is just not predictable at all, no matter how good we are with math and how hardly we compute. Does such a pure form of randomness exist? We don’t know. For example, we don’t know if events such as the decay of radioactive particle may be truly random or just unpredictable.

On randomness and models: engineering approach.

We make models to predict events. Our models are used to predict, say, the lifespan of a light bulb, the weather in a region or the interaction of two molecules we never tested. We can proceed in the following way: let’s postulate that pure randomness does not exist, but just unpredictability. Even if we are wrong, we can assume that and do our best to reduce the random part (the part we have no clue to predict) of the phenomena we study.If something is just too complicated to compute, then we call it random and sample its probability. Take the classic examples of the dice and the coin. With a proper (complicated) physical model and a lot computational power, we could predict exactly the outcome. With a good model and a huge (for actual standards) computational workload, we could even predict the roulette results! It’s just physics, the die rolls, the coin flips. We just assume a outcome probability of 0.5  for each side of the fair coin, and 1/6 for each fair die face because it’s a lot simpler. Probability, from this point of view, it’s just a very basic way to model phenomena.

Ironically, from the model maker point of view, randomness is just a feature we have to care about, a feature to model (for example, there are different kind of classified noises in signal theory). As someone said long ago, all models are wrong, but useful to some extent. Therefore, it is important to narrow down the unpredictable (random) part of the model as much as possible. There will always be an error in the predictions, but as long as the error is considered small enough to avoid affecting the results in a critical way, it’s ok.

Dec 22nd, 2010. Winter solstice. Our totem animal is the Bonellia Viridis.

Description: Bonellia Viridis, also called Green Spoonworm, is a worm living in salty waters. Its sexual dimorphism is astonishing: while the female is up to 8 cm long, the male is just 1 to 3 mm. The larvae have no sex: sex is determined on a geographical base. Larvae, in fact are released into the water: if a larvae ends up on the sea-floor, it will hook to the ground and grow as female; if a larvae lands on a bonellia viridis female, is engulfed. The hormones in the female body will turn the larvae into a male, whose body is manly occupied by its sexual organ. The male will spend its life inside the female body, as a parasite, with the only function to provide gametes.

The animal was first described by the Italian biologist Luigi Rolando, who name it after his friend Franco Andrea Bonelli (bonellia) and the latin for green (viridis).