On May 20, news was released that has caused demonstrations of both joy and complete dismay: the creation of a bacterial cell controlled by a synthetic genome. What are the background of this research and its possible consequences?
I can affirm – and I do not hesitate to put my hand in the fire for this – that we are experiencing the beginnings of what will be known as the era of molecular biology, which will have an impact perhaps greater than or at least equivalent to the discovery and development of atomic energy that took place in the first half of the 20th century. Over the past few decades we have accumulated an enormous and invaluable amount of data on the nature of genetic information. Our knowledge is especially strong in bacteria, which are the simplest and most abundant cellular organisms on Earth. We have a pretty clear idea about how bacterial genes work, how they interact with each other, in what patterns—depending on environmental conditions—they turn on and off, and how these microorganisms acquire new genetic information. To this framework of knowledge we have to add the immense arsenal of notions that we have obtained through the analysis of the more than 1,000 bacterial genomes that have been sequenced to date. This arsenal is especially relevant, since it allows us to analyze, similar to what an engineer does when reviewing the plans of a complex building, the life plan of an organism. A growing group of researchers affirms that we already have a body of knowledge of such magnitude that we can make our own designs based or inspired by what happens in nature, and consequently they assure that we are at the door of what today, of In a perhaps somewhat presumptuous manner, but certainly not unfoundedly visionary, it is beginning to be called synthetic biology.
Genetic design
The term synthetic biology It is not new in scientific language: it emerged in the 80s to refer to the technology required for the production of the first genetically modified bacteria that had one or a few genes outside their original genetic heritage; However, today the term has a much broader connotation, since it refers to the science and techniques used to design and build gene blocks that give organisms new characteristics and functions that do not exist in nature. And by that I mean not only the modification of microbes so that they have, say, the ability to degrade synthetic compounds or produce biofuels, but also, ultimately, the creation of new living organisms, designed on the desktop, and then generated from chemical ingredients obtained in the laboratory.
Having said the above, it seems very likely that conflicting judgments will arise: thus, some will believe that we are facing the new Frankenstein; For others it will be the end of vitalismphilosophical position that maintains that life is not created, it is transmitted, and, therefore, ensures that the vital principle in some way it is independent of the structure of the cell.
In general, biologists agree that all living beings must meet three requirements to be considered truly alive: first, be capable of self-maintenance, that is, have a metabolism; second, being able to reproduce; and third, possess the ability to evolve. This is very easy to say, but establishing exactly what compounds, what genes and what proteins are required to meet those three requirements is something very different.
One of the most controversial points of view held by scientists involved in synthetic biology is that they claim to have an experimental approach to solve the most important dilemma in biology: understanding the fundamental principles of the phenomenon we call life. His proposal is that if we want to know what life is, we have to synthesize it in the laboratory, under strict experimental conditions. The first firm step has already been taken.
artificial organisms
On May 20 of this year we received extraordinary news, which will surely change the course of biology as a science and will have, in the not too distant future, enormous repercussions on our daily lives. That day, Daniel Gibson, Craig Venter and 22 other scientists from the J. Craig Venter Institute in the United States published, in the influential journal Science, an article whose title sums it all up: “Creation of a bacterial cell controlled by a chemically synthesized genome.” And it sums it all up because, in other words, reading the article reveals several transcendental firsts: that, for the first time, the genetic material of an organism (genome) is designed by methods bioinformatics (computational); that this genetic material is chemically synthesized and transplanted into a host cell, to give rise to a new organism whose functions depend exclusively on the instructions that were introduced. The most enthusiastic scientists believe that this is the first time that life has been generated in the laboratory; The most conservative even agree that this is an initial but firm step towards creating a completely artificial living cell.
The beginnings
The article that appeared in Science is the result of many years of hard work, during which countless obstacles had to be overcome. Most likely, the genesis of this project occurred when Craig Venter (see box) set out, 15 years ago, to determine the sequence of the genetic material of the pathogenic bacteria. Haemophilus influenzae. With current techniques, this goal could have been achieved literally in a few days; However, a decade and a half ago, obtaining the complete DNA sequence of a bacteria was a visionary, complicated and high-risk project, since at that time the first automatic DNA sequencers were just emerging, and there was a lack of computational tools to quickly face the problem. Many consider that the birth of genomic sciences actually took place much earlier, on July 28, 1995, the date on which the article reporting on this project was published.
having chosen Haemophilus influenzae As an object of study it was a very intelligent decision, since it is a bacteria that can grow in laboratory conditions, whose genome was known to be small and, therefore, easier to sequence. A few months later, Dr. Venter and his team determined the genome sequence of another bacteria, Mycoplasma genitaliumwhich also grows in the laboratory, but in much stricter conditions than those required Haemophilus, despite the fact that it has a much smaller genome than the one the latter has. The underlying idea in these projects was to determine the minimum number of genes required for a cell to be considered alive. In 1996, and after careful comparative analyzes between the genomes of Mycoplasma and Haemophilus carried out with bioinformatic tools, doctors Koonin and Mushegian, from the National Institutes of Health (NIH) of the United States, estimated that this minimum number is 256 genes. Ten years later, Craig Venter and his collaborators decided to experimentally compare this approach. To that end, they insisted on destroying the genes of Mycoplasma genitalium to determine which genes are essential for life and which are not. Thus they established that 100 genes of this bacteria are completely dispensable, and came to the conclusion that only 425 genes are needed to generate an organism with independent life, more than those predicted by Koonin and Mushegian, but still a ridiculously low number of genes. for a phenomenon that was considered intrinsically complex. With these numbers in mind, Venter realized that it was conceivable to chemically synthesize a small genome and “give it life” by transplanting it into a host cell. Since then, that is, since 2006, Venter and his team dedicated themselves to establishing the scientific protocols to make this dream come true, which happened four years later. From the beginning, it was perfectly clear to this group of scientists that two key problems had to be solved, which, furthermore, could be solved independently of each other. The first was to establish how a genome could be transplanted into a host cell and ensure that it replaced the original and thus “took” control of cellular functions. The second focused on how to chemically synthesize a genome.
Who is John Craig Venter?
The least that can be said about the American scientist Craig Venter, born in 1946, is that he is a controversial character; Some call him a pedant and even a huckster, others claim that he is the most influential scientist of the century and that his vision is changing the way science is done. His perspective on the relationship between science and industry is also radical and that is why he has made more than one enemy. Venter, a biochemist by training, received a doctorate in physiology and pharmacology from the University of California in 1975. He worked initially at the State University of New York and then at the United States Institutes of Health, where he raised the importance of identify genes that play a fundamental role in brain physiology. To this end, Venter determined the partial sequence of an enormous number of genetic messages (messenger RNAs) that are synthesized in that organ. Venter, in a highly publicized move, attempted to patent these genes, but fortunately the courts did not allow him to do so. A few years later he co-founded the company Celera Genomics, and there he became the first scientist to obtain the complete genomic sequence of a living organism: Haemophilus influenzae. He achieved this through a novel strategy called shotgun sequencing, which combined the power of automatic sequencers with those of bioinformatics. With this experience in hand, Venter challenged the international consortium that was in charge of sequencing the human genome, stating that he would accomplish this goal in much less time and at a lower cost. And so it was: he sequenced the human genome, his own, in record time. This company also sequenced the genomes of the fruit fly, mouse, rat and dog (Venter’s poodle). Venter was forced to leave Celera Genomics when it was concluded that this type of information could not easily be monetized. In another contribution, Venter set out to explore the microbial diversity of the oceans through the massive sequence of the genomes of the microorganisms that live there. This novel strategy for describing the bacterial components of an ecosystem is now known as metagenomics…