Paste and cut to create life?|Profile

Those of us who write this book (all eighty -and -year model, jewel, never taxi) belong to the millennial generation, that, in general, was not born with a computer under his arm, but learned to use it in childhood or adolescence.

We know what life was like when music was heard in a walkman and to make plans with a friend you had to call it the fixed, but we also easily adapted to the digital world and hyperconnected of the last decades.It is very likely that we find differences in the way we live the technological revolution if we consult a person from the generation of our parents (who later arrived in the digital world) or from which we follow us (the digital natives).However, we will all agree that technology has radically transformed the way we live and think.Sciences in general, and life sciences in particular, have not been the exception.

To understand the relationship between biology and technology, we must go back to time ago.If we ventured to think about the origins of biology (when it was not yet called biology), we will find that the first approaches responded to the need to preserve the large volumes of fruits and grains generated at the beginning of agriculture,More than ten thousand years ago.Later we developed processes that we used until today, such as fermentation to make beer or bread.Quite later (around two000 to.C.) comienza a tomar forma en diferentes puntos geográficos (Mesopotamia,China y Egipto) otra de las disciplinas de la ciencia de la vida: la medicina.At that time, it was still far from its current form and it was a kind of mixture between magic and a certain rational science.The paradigm shift would reach the end of the European Renaissance and beginning of the modern era (between the seventeenth and eighteenth centuries), when biology became something similar to what we currently studied in schools and universities.At this point the biologists (then called doctors, botanists or naturalists), without seeking an immediate application of knowledge, dedicated their works to describe life with scientific rigor.

Life sciences crystallized in anatomy manuals, herbariums and bestiaries.These works were possible thanks to the development of mechanisms and devices that allowed expanding the limits of the known.And, in turn, this new knowledge led to produce better devices.The indispensable synergy between science and technology.

Only with the arrival of the nineteenth century, biology would definitely become a modern science.At the same time, two great scientists worked in parallel to try to understand how life had diversified on our planet from the first organisms formed by a single cell to birds, mammals and other living beings that exist today.

Por un lado,Charles Darwin embarcaba a bordo del Beagle para su travesía por la costa atlántica de América del Sur.On the other, Alfred Wallace was on a journey through the Malay archipelago.None knew what the other worked (there were almost two hundred years for social networks to exist!), What makes it even more wonderful that they have reached the same conclusion.

Those ideas gave rise to the paradigm of the evolution of species, which crossed life sciences since then.At this point, it is worth asking: what does preamble come so?The reason for this brief review of the history of life sciences is none other than to show the multiple transformations that its reason and form of study has suffered over time.The naturalistic vision of two centuries has given way to another way to study the biology more oriented towards the data.This paradigm change becomes preponderant the role of information technologies, of which biology nourishes to form this new discipline that is bioinformatics.

Bioinformatics is the axis of the book, but also, in a way, it is an excuse to tell how scientists work to try to understand the enigmas of life.

In the next pages, we will analyze the route that life sciences have made until they become information sciences, assisted by some young disciplines (such as computer science) and others quite veteran (such as mathematics).We will see how this heterogeneous science group allows us to get closer a little more towards the understanding of some specific aspect of living beings functioning.We can explore what happens inside a cell with the simulation of molecules movement and its interactions from the computer screen.Or study how cells of different types are grouped to form a tissue and an organ.We can even go to a much larger scale to analyze how the introduction of an exotic species in a natural area can decrease populations of native species.

As our knowledge of biological systems grows, one of the classic arguments of science fiction becomes more feasible: Can the human being create life?Or, in this case, can we design life from a computer?Although it seems distant, every day we are a little closer to this is feasible (do not try in their homes!).

Working with computers has an additional advantage: it is relatively cheap when compared to the costs of having a laboratory in operation.During the development of a new medicine, thousands of candidate compounds are usually on the way, because they do not serve what they should or have too many adverse effects.If each of those candidates had to prove in the laboratory, we would be talking about a considerable time and money investment, but fortunately much of the tests can be carried out on computers, so that only the most promising reach the preclinical and clinical trials.

In summary, bioinformatics deals with the creation of simplified models of reality that allow us to better understand a phenomenon and perform predictions on the behavior of the system in case something changes.This is a book about life but in bits!()

Big Bang?No, Bío Bang for a long time, biology wondered how living organisms work.A long time, here, it is a euphemism to refer to almost the entire history of humanity, from the first theories about life to the present.Understanding systems from critical observation and by applying the scientific method has been the engine of biological sciences for years and allowed to carry out many biotechnological advances.

¿Pegar y cortar para crear vida? | Perfil

Understanding the system offers the ability to manipulate and improve it.That is why today we have well -differentiated biological products from its ancestral forms.We have been able to select more red and juicy tomatoes, more leafy and appetizing lettuce, more dwarf corn plants and with greater production of grains and a practically endless list of etceteras ranging from plant grafts to the domestication of animals.

Despite the obvious advantage that we have known.This has to do with the fact that, for most people, it is much easier to learn by doing.The question that prevails in this section is, then, can biology be done?Can life be created?

In the previous chapter we discussed different ways of modeling life.Synthetic biology is, for many, a capricious proof of concept whose purpose is to show the ability of these models to reproduce reality.For others, it is a rising field that allows exploring a new biological question: how could live organisms be?

Imitate biology

For those born in the 1980s, Tamagotchi was a part of childhood almost safely.It was an electronic toy that fit in the palm of the hand and had a screen and a couple of buttons.The goal of the game was to take care of a pet, since he left the egg to his death, which involved feeding him, playing with her and taking care of her if she was sick.

A mediados de los años 90 surgió un juego de computadora llamadoCreatures, que llevó esto un paso más allá: había que criar a una raza extraterrestre y ayudarla a sobrevivir.Cada individuo estaba manejado por una inteligencia artificial, por lo cual podía aprender cosas y responder a los estímulos que se le presentaban.Not only that, but each one had their own DNA that could mutate and evolve in the following generations.Como un individuo vivía un promedio de cuarenta horas, era sencillo seguir los cambios que aparecían en una población a través de las generaciones.For younger audiences, perhaps titles such as Spore or Plague Inc.are more familiar.

In the first, the player begins as a lower unicellular life and acquires, throughout the development of the game (which emulates the passage of evolution), new biological tools to survive in new environments, while in the second, thePlayer must administer the virulences of an infectious agent to infect everyone before scientists find a cure.Imagine the relevance of epidemiological models, which we saw in the previous chapter, to recreate this type of simulators.While these games do not try to be realistic or biologically correct, they serve as an approach to the idea of simulating life.

A very nice little worm

Since computers allow it, the idea of being able to simulate the functioning of an organism is something that has aroused the attention of scientists.Crear un Tamagotchi realista de un organismo nos daría la posibilidad de estudiarlo exhaustivamente, modificar los estímulos o el ambiente para ver “qué pasaría si…”.

Con esta idea surgió el proyecto internacional OpenWorm a principios de two011, que trabaja con un gusanito llamadoCaenorhabditis elegans, oC.Elegans for friends.This cylindrical body worm and a millimeter in length is one of the simplest organisms among those that have a nervous system.

The objective of this project is to build a complete and biologically realistic emulation of the worm, in addition to deciphering all the path of genes involved in their behavior.For this, they have a lot of information, since it has been very studied since the 1970s: it was the first multicellular organism whose genome was completely sequenced, and the map of all connections between its neurons is also known (the connectoma).

The OpenWorm allows exploring all the cellular cellular anatomy in 3D.

The long -term objective of this consortium is the simulation of large biological systems, such as the human brain.In fact, they have already taken another step forward in two016: with the Neurkernel project, the brain of the fruit fly has been simulated.

A similar idea led Stanford researchers to find a way to model an intracellular parasite called Mycoplasma genitalium.This bacterium lives in the genital tract and is spread through the exchange of fluids in unprotected sex.It has a small genome, composed of 5two5 genes, and has been widely investigated by groups of scientists around the world.

The Stanford team unified all the information about the parasite in more than nine hundred scientific publications.This included genome data, RNA, proteins and chemical reactions that occur inside the cell.On the basis of this information, they built a virtual cell consisting of twenty -eight functional modules that operate independently but communicate with each other to coordinate tasks.

Rethink life from life

We can abstract life, as a concept, to a set of microscopic machines that work coordination to perform complex processes.All these machines are scheduled to do something in particular.We know that the function of a protein, for example, will depend on its three -dimensional form, and this, in turn, on the amino acid sequence that composes it.Now let's observe this issue of life manipulation with bioinformatics eyes.In short, if we take the metaphor to the limit and think of the cell as a computer, we could propose that each gene is a program and that, from the coordinated operation of these programs, we take out a walking organism.

If everything we know about genetic manipulation is true, and we continue to deepen the metaphor of the cell as a computer, it is worth asking: can we install a set of new programs and have a new life?This question was the engine of the first Biosynthetic experience in history and detached from a job that we explore previously.

That in silico model of Mycoplasma genitalium was used to develop the first purely synthetic genome and, with it, the first human design life.To do so, the researchers took the genome of the bacteria and, on the basis of the previously described model, eliminated from this all non -essential genes (that is, all those of which the bacteria could do without).Thus they obtained a new genome with the minimum and indispensable amount of genes.Then, they transferred this synthetic genome to a mycoplasm cell caprolicum, a related bacterium.Shortly after the transfer, the cell would account for the surplus genetic content and would be divided into two daughter and sisters cells.One of them would be Mycoplasma Caprolicum and the other would be the synthetic cell: Mycoplasma Laboratorium.

En este nuevo organismo, los investigadores del InstitutoCraig Venter, autores del trabajo, se dieron el lujo de agregar al genoma una serie de marcas de agua para controlar el éxito del experimento, pero sobre todas las cosas para radicalizar su impacto.The water marks were four:

1.An HTML pseudocode (that is, the one used by Internet browsers) with a congratulation to the one who had sequenced the genome of M.Laboratorium.

two.A list of some work authors, with an appointment of James Joyce that says: to live, to err, to fail, to trump, to recreate life out of life, which could translate such as living, erring, falling, falling, falling,triumph, recreate life from life.

3.Another list with more authors and an alleged appointment by Robert Oppenheimer: see things not as they are, but how could they be.

4.And finally, another list of authors attached to an appointment of physicist Richard Feynman, who would crown the work: what I cannot build, I do not understand.

Learning by doing

So far, all very well with this to grab a genome, clean it a little and plug it into another bacterium, but is it possible to introduce new behaviors in an organism?This is the approach proposedeven or that we will never see.

The first historical milestone we have to attend comes from the hand of genetic engineering: the ability to edit genes and genomes.Even when it still had no official name, in the early 1970s, genetic engineering would take its first step in this regard, with the discovery of restriction enzymes, found for the first time in insulation of chimpanzee cells and later described describedFor virtually any way of life that can be imagined.Restriction enzymes are protein capable of recognizing and cutting, usually with a high degree of specificity, certain DNA sequences.His name responds to that this peculiar function is, in fact, a defense mechanism against foreign DNA molecules, such as a virus.That is, when the cell was attacked by one of them, there would be an enzyme capable of destroying that DNA chain before it was too late.There are many enzymes of this type, with different tropisms (that is, with different preferred sequences to cut), and that suggests that, if we know the sequences that we want to edit, we will almost surely find an enzyme capable of cutting it.For that, then, once we have the DNA cut, we will need what we want to paste between and something to, effectively paste it.The element that will link our genetic collage will be a ligase, an enzyme capable of generating the necessary chemical bond to join two DNA chains.

Here they can ask what one would like to cut and paste a DNA sequence.The answer is that, although writing directly the genes or genomes inside a cell can be complex, it turns out that copying and paste genes is relatively simple.Como hacer un trabajo práctico robando párrafos de Wikipedia… pero con genes.And for the good of analogy, then, we will need a genetic wikipedia.

That is, a place where we can copy a gene.And this will take us to our second milestone, which already arrived at the dawn of genetic engineering, averaging the 1980s, and that would be nothing less than the development of a technique known as PCR (its acronym in English, Polymerase Chain Reaction [Polymerase chain reaction]).This technique allowed, and allows, copying a specific region of DNA, generating a high number of DNA copies in a very short time (1-3 hours, depending on the length) and increasing exponentially in time the amount of DNA in a sample contributingMuch material for our collage.Third, and not least, automatic sequencing, in which we have already abounded in previous chapters, allowed to read and obtain with a high degree of specificity the sequence of small DNA segments.This implies that we can identify and copy virtually any sequence of any organism.These last two milestones will be our wikipedia, and the editing tools will allow us to make all kinds of molecular grafts.

In this way, we will be able to insert small DNA segments into specific regions of a gene or an entire genome.We can make a corn plant have a banana gene, or that a fluorze bacterium adding a fluorescent jelly.Copiar y pegar.Although this technology could not be considered synthetic biology per se, it has been a fundamental tool for us to be talking about the change of paradigm proposed in this section.If we can modify life, we cannot be so far from creating it ex novo.

Program Biology: Biobricks

Genetic engineering provided the necessary tools to introduce changes in DNA sequences and, thus, create organisms with new characteristics.Is it possible that computers are allied when designing these changes?To start answering this question, the most important thing is to understand that synthetic biology implies designing a genetic program.This program must be inserted into a cell to be interpreted.When producing our genetic programs, we will need a unified and well structured language that literally allows us to program life;that is extensible to any biological function that we can think, and with which a wide variety of biological programs can be designed.Con esto en mente, se desarrolló de forma comunitaria un lenguaje de programación al que se bautizó como “lenguaje abierto para la biología sintética” (o SBOL, por sus siglas en inglés).The define feet components called biobicks that function as blocks.Literally, the Bricks component in its name refers to blocks (or bricks) in English.We can think of these blocks as assembly bricks.Those of us who have the luck of having a bucket of bricks as littleto your preference infant).Like bricks, biobicks can be combined differently and lead to various behaviors, as instructions would do in a computer program.Con ayuda del SBOL, empezaron a aparecer abstracciones que permiten modelar los comportamientos de los organismos vivos, sin depender específicamente de una especie (o modelo biológico) en particular, lo cual es de gran utilidad para diseñar comportamientos biológicos sin depender tanto de procesos o fenómenos específicos de cada forma de vida.All these elements enable scientists to think and use cells in a predictable and pseudodeterminist way, a quality that is imposed among the most important in the computation processes that computers carry out.

Ladrillitos to build genetic programs: the promoter will recruit transcription machinery, regulated in some specific way, to express a fluorescent green protein.Thus we will have a kind of sensor that will fluoresce when the regulator condition is met

Synthetic biotechnology

Although we are facing an incipient discipline, the applications of this technological promise have not been expected.There are already functional prototypes of life forms specially designed to monitor biomolecules concentrations (biosensors), with applications ranging from diagnosis to ecological surveillance;to optimize metabolic routes (engineering), of high interest in industrial processes and mining enterprises;To operate as a microcomputers or logical gates, with high impact potential in microelectronics, and even as forms of information storage.

Como casi siempre que aparece algo que rompe los moldes de lo que sabemos y podemos hacer, las promesas son muchas y, en la actualidad, la biología sintética es un mercado que mueve two mil millones de dólares anuales en inversión de riesgo.Time will say if it's just promises or if we are about to enter a new era for biotechnology.

A bioethics stop

So far, we have tried to spiny some rudimentary concepts of molecular biology and genetic engineering to build the idea that we can not only understand life and make models about its functioning, but also manipulate it.

The famous phrase that great power entails a great responsibility is appropriate to think and rethink everything that has been explored in this chapter and everything that has probably been titling in the reader's imaginary.Como muchísimos otros saltos tecnológicos en la historia de la humanidad, es necesario que tanto científicos como ciudadanos interpelen el desafío ético que implica la capacidad de crear vida y, fundamentalmente, la necesidad de hacerlo de un modo responsable.

☛ Life title.exe

☛ Author e.Launchti, l.Uran Landaburu and M.Banchero

.☛ Editorial FCE

Authors data

Esteban Lanzarotti es licenciado enCiencias de laComputación y doctor en Química Biológica por la UBA.

Lionel Uran Landaburu has a degree in Biotechnology and performs his doctorate at the Trypanosomatidos de la UNSAM Genomics and Bioinformatics Laboratory.

MartínBanchero es licenciado enCiencias Biológicas por la UBA y máster en Bioinformática y Biología de Sistemas de la universidad Uva-vu de Amsterdam.

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