Let me introduce you our panelists. Dr. Carlo Alberto Cossano. The Italian names are incredibly beautiful. Dr. Carlo Alberto Cossano works as health informatics project manager. He is an expert in clinical pathology analysis laboratory and pathological anatomy laboratyor information systems. He works in the Dedalus Healthcare Systems Group in Italy. Dr. Carlo Alberto Cossano’s will lecture on the topic: “Informatics records and proteins production.” The floor is yours. Thank you.

 

So, good afternoon. I am glad to be here. I am honored. And I am basically a technician. So I will be a little thechnical. So pardon me.

 

We're living in the Digital Age. It's really hard, if not impossible, to find a process that is not in some way managed, controlled, administered or enhanced through the use of a computer program or a database or any software application.

In these contexts, the computer, database or system programmer or operator has often a pleasure and pain to live with: “the record”, defined in the usual jargon.
Very simply put, the record is a collection of information, that can be both complex and simple, ample or reduced, structured in one or more field or parts, the base unit of a computer archive.

 

Making an example: in a set called “people”, formed by several records, the single record may contain two fields, the field “name” and the field “surname” but even the “sex” and the “date of birth” fields.

 

When we add a record similar to another introducing a variation in its content

we use quite often a codified information, usually quite simple,

that allows us to organize and interpret the information already or potentially present in the record itself: the “state.”

Introducing another example that we will recall later, supposing that I want to insert a record for every new account in the archive or database of a bank and I have to maintain a record of every closed account, I need at the very least one field in which to write “O” or “C” for identifying both the “open” and the “closed” states; if I should need to consult the archive for a feedback on the number of closed or open accounts it would be enough just to (a) create the the above field in the record, (b) fill it with the correct information in the correct moment and (c) recall that information, that specific record “state” at the very same moment in which I need an “output” to my “query.”

[PICTURE 1]

 

It's normal to come upon these considerations and logics examining details of the information management approach regarding computer programs and databases: we have these solutions today, having reached the peak of the information age, thanks to decades of enhancements applied by intelligent beings with that specific purpose, so what we have is the best of what intellectual and technological growth can develop in years and years. But it may seem less “normal” to find out that these very same logics and considerations, that we’ve just described as the product of years and years of applications by the most clever being of the planet, are fully adopted in biological processes operating in the cells inside our body, as in those of every living organism.And this happens since the appearance of the first “simple” unicellular life forms, with logics and processes fundamentally unchanged from the extant ones.Proteins production requires a state managementEvery living being is made of cells; every cell is made of proteins (or of their products).

Proteins aren't “substances”, as how sometimes are simplistically defined; granted, from a certain point of view everything is a “substance”, even the computer that we use when we surf the Internet, since substances are constituted by atoms, and atoms are the fundamental building blocks of matter.

Proteins are rather electrochemical mechanical (and, as we will see, even information processing) mechanisms that constitute, assemble, regulate, maintain, manage, transform create and destroy (and much more) cells and tissues of any living organism (and even of any “un-living” one, like viruses).

Their almost boundless diversity is remarkable: it’s been estimated that inside of the human body there are at least 25.000 different kind of proteins, every one with its specificity that can be connected to a moment, a purpose, a quantity essential or concurrent to the completion of a certain function.What prepares and produces proteins in the cell? Very simple: other proteins, themselves prepared and produced in the same way.
But, if we make an analogy, it will be easy to grasp that for a production line that must continually an according specific and highly variable requirements churn out something as 25.000 different pieces you need to manage the production flow, in some way.

The amount and diversity are so high that a “production problem” in such a “factory” would mean not only an halt in the production line, with a following money loss, but the very same, cost the life of the cell and maybe of the entire organism.
It becomes clear that it’s essential to have the pieces production line under control, managing the differents phases, maybe having the information of the point at which the single piece is in the production phase: a state management.

State management and information

When a software program must control records variations it’s essential that a programmer assigns semiotically a condition to an information and structures the software to allow the management of that condition.If I would want to use my program to manage the production of a car in the final steps of its construction, say for example during the painting process, I may ensure that (a) some optical sensors recognize the entrance of the car bodies in the painting basin, that (b) other proximity sensors activate drying fans for the bodies that are already painted, that (c) a timer stops the drying process and (d) a weight sensor involves the activation of carrying robots designate for moving the painted models to the next production step.

 

If my program would follow every car body passing this phase, I could create a specific field named “Painting_State” in the database used by my program, in which it will be saved the information received from the various transducers with four different letters, “A”, “B”,”C”, ”D”: with a simple function that compares the records with the state “A” with the ones having the others I could know in real time how many cars I still have to paint, how many are painted and how many I deliver to the next phase.
I believe that this simple example could adequately represent the usefulness of the state management in informatics and its countless applications.
This powerful tool of assigning “meaning” and “purpose” to simple letters - though used within the appropriate context and the proper tools, allows to increase tremendously the amount of feedback information from a process managed with it: I can control every aspect of the quality in my production, as speed and precision, calibrating it on the requests flow, of the personnel, the environmental context, the raw material supply, and so on.
Potential is almost limitless if behind those “letters” there's a need, a project and a mechanism that allows its management: to utilize to the full this potential it's clearly essential that an intelligent - and competent being modifies the program inserting the instruction needed. A record state in the RE and in the Golgi apparatus. Cells are constituted by several discrete components that perform different functions, called organelles.
Among them, endoplasmatic reticulum (ER) and the Golgi apparatus (GA) are very important on proteins production and dispatching inside the cell.

Proteins being “wrought” and distributed through these two electrochemical mechanical marvels, ER and GA, circulate inside them using vesicles that become detached from and attached to the organelles membranes using others protein functions that we will not consider in this present lecture.Simplifying with another analogy taken from the previous ones (inevitably a little more complex), proteins could correspond to a car that must be completed in an assembly line, ER and GA to the assembly line and the vesicles to the transporter robots designated for the circulation of the car “under construction”.

How can all this flow of preparation, mounting and distribution be controlled?

An informatics engineer today would propose to do it with a software program which easily allows a state management in the various phases of the car production.At this point let’s introduce the heart of the matter: the real incredible thing is to find that this solution, resulted from decades of enhanced applied intelligence, thought and proposed by an expert and competent intelligent human being, is exactly what happens inside the cell through the use of specific sugar chemical compounds, called oligosaccharides or N-glycans, able to provide semiotics, a precise and straight information on the state i.e. the phase at which a protein is arrived in a certain moment.

 

Let’s compare so the proteins to the records and these sugars to the field that contains the information related to the state of the record itself and let’s see if the analogy fits.
These sugar chains are prepared and “attached” on the folding protein as some kind of a “mounting diary” that will accompany them through all the following phases till they will become detached as unnecessary.

 

[PICTURE 2]

Before being used as “mounting diary”, these chemical structures must be built and connected to the nascent protein or the protein in some production phase; only for preparing the oligosaccharide,

15 different proteins intervene, all coordinated in precise moments and designated to perform specific modifications to the sugar chain.

[PICTURE 3]

 
Once concluded, this huge work of synthesis allows the carrying out of the state management function, an essential function added to those that constitute what is defined by biologists and biochemists as a real “Quality Control” system, working inside the cell in the ER and GA, system that is described in a technical paper as it follows [2]:

“The QC system is adapted to handling virtually any condition that results in a protein conformation other than the native state. Accordingly, multiple scenarios of QC arise from the many ways in which proteins can fail to achieve their native conformation”.Therefore a system highly complex, able to manage and act automatically on the “quality” of the production in relation to every possible scenario that would materialise, an extraordinary thing for a process capable to produce more than 20.000 different “pieces”.For example, some proteins require oligosaccharides for the folding properly in the ER. Furthermore, oligosaccharides even confer stability to several secreted protein structures, as well as favour their preparation and transport. In addition, cells adhesions are facilitated if there are oligosaccharides on the proteins that serve as “hooks”.

 

[PICTURE 4]

In short, every oligosaccharide modified form has both chemical, “structural” and “semiotical” characteristics that are, recalling our main theme, essential to the nascent protein production process. Sugar structure is transferred on to the protein and linked to a special part of the constituting amino acids sequence, acting then as a block or as a “promoter” for others proteins adhesion, proteins used for sorting and management like lectins homologues calreticulin and calnexin, thus even indicating at which “point” of the production the nascent protein has arrived.Additionally, exactly as it would happen in our car painting example described above, there's no guarantee that the painting process would not be completed if the transducers that signal the car body passage would be inactivated, but anomalies on the final result quality may occur, as well as management problems of the entire process, resulting in unsellable products.In fact, in laboratory experiments where synthesis of oligosaccharides portions is inhibited, proteins are still produced but they don't fold properly (so they result to be not functional), accumulate in the ER and are less stable: in short, “unsellable”.Adaptation or irreducibly complex innovation?

The paragraph cited above describing the quality control system, has used a term to indicate how a set of these kinds of systems may have appeared in living organisms (assuming that it may have done so after the same living organism itself): that term is “adapted”.Actually we don't want to raise doubts on the fact that organisms are able to adapt to environment changes, selecting the more fitting “versions” depending on the various context. But adaptation doesn't create biological novelties: at these level of complexity, nothing that wasn't pre-existing has been observed experimentally “arise” from precedent or different systems. Indeed, biological novelty so complex, with functional constraints requiring simultaneously and holistically expressed functions, it’s described by intelligent design theorists as “ irreducibly complex”, as a whole or in its parts.

 

After all, in an evolutionary context, to explain why oligosaccharides are used for state management as it occurs in informatics one should not only invoke prohibitive probabilistic arguments of selection of the correct sugar structure useful to manage all the various “transitions” but even for all the systems that prepare that specific structure (and we’ve seen how this process is complex and structured) as well as for all the machineries that utilize the informations that it represents and its biochemical design, with their stability characteristics.

It is true that so called evolutionary adaptation operates step by step, selecting the most beneficial “version” of the “program” - using informatics terms - but it’s exactly this condition that makes extremely difficult to demonstrate logically and experimentally evolutionary “jumps” essential to these transitions.

A complete function which brings advantage at every single hypothetical step must be identified, steps to obtain the oligosaccharides structure and all the specificities of the hundreds of molecular machines connected to them and which operate behind a system like this. It’s easy to understand how the sum of all these probabilities that must bring an advantage at every single selective “step” makes too far implausible an hypothetical scenario in which the required biological information parameter is overlooked, even without analyzing the details behind these steps.

 

Exactly as you would refuse to believe to someone that would try to convince you to have guessed your phone number making casual phone calls, the factors of (i) scientifically accepted available time since the appearance of life on earth, (ii) the mode of “exploration” of the probabilistic space that evolution adopts, (iii) holistic complexity of the systems to obtain render an hazardous fairy tale assume the appearance of such a process without being able to observe it or prove it, but just because it has to be the only way to achieve a result. So, can we assume a simpler oligosaccharide, with less managed “states”, to place in the “evolutive ladder” as a precursor of the extant forms? Very complicated, for several reasons that we can summarize resuming our analogies. How could a quality control system work if it would verify, for example, just the entrance and the exit of the car bodies?

Oligosaccharides are not an analogy with the state of an informatics record and all that surrounds it: they are real molecular support for biological information management, being automatically prepared by the very same proteins which they help to build.