A tale of enzymes and sun

By Martín Bonfil Olivera

Published in Milenio Diario, august 4, 2010

Sometimes, evolution plays dirty.

Once upon a time there was a planet (ours) where, about 3.5 billion years ago, life emerged. But the first cells confronted a problem: their star emitted, apart from visible light, a respectable amount of ultraviolet rays. And this high energy radiation normally damages complex molecules, like the nucleic acids that store the genetic information. The result: mutations and death. Life was tough in those days.

In the course of evolution, millions of years later, photosynthetic organisms that released oxygen (O₂) emerged. About 2.4 billion years ago, the Earth's atmosphere was became full of this gas. Part of the oxygen, high in the atmosphere, reacted to form the famous ozone layer (O₃), that protects us today – although not fully– from the excess of ultraviolet radiation.

But evolution could not wait for an ozone layer. Way before that, some adaptations emerged to repair the damages that ultraviolet light caused in the cell's DNA. One of the most efficient ones was the enzyme photolyase: a protein that, activated by the visible light from the sun (hence the suffix,"photo"), reverts the damage in DNA (specifically, it breaks thymine dimers: abnormal bonds between two "steps" of of the spiral ladder of the double helix, so that when genetic information is copied into the next cellular generation, it causes mistakes: mutations).

Photolyase was so successful that today it is found in almost every living organisms: bacteria, fungi, plants, fish, insects and some mammals, like marsupials (such as kangaroos, which carry their immature babies in their bags). But -and here comes the cruel evolutionary prank– something happened along the way. One of the branches of the tree of life suffered a mutation that eliminated the photolyase genes. As a result, humans, and all other animals with a placenta (placentals), lack photolyase, thus making us more susceptible to skin cancer. This is why we depend on sunscreens when we go to the beach or when we walk in the street in sunny days.

Fortunately, last week, Nature magazine published the work of a Chinese researcher, Dongping Zhong, and his team, from Ohio State University, in Columbus, where they describe the detailed molecular working of the repair mechanism of photolyase from the fruit fly Drosophilia melanogaster. With this and other studies, it is possible to visualize the use of this enzyme in creams that protect us from skin cancer by repairing the damages that ultraviolet light causes in the DNA of our skin cells (it has been demonstrated that photolyase can be applied to the skin inside liposomes –fat vesicles– in in the form of cream and has protective effects).

Basic science thus gives a possible solution to an evolutionary injustice. All in the name of a good tan.

(translated by Adrián Robles Benavides)

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Still, Influenza

By Martín Bonfil Olivera

Published in Milenio Diario, July 15th, 2009

Science does not reveal absolute truths, but it does have a commitment to reality.

A good example is the pandemic -started in April in Mexico as an epidemic- caused by a swine A/H1N1 influenza virus.

Mexicans remember how, after the emergency stage that forced Mexico City and other places to shut down schools, restaurants, cinemas and other gathering places, there was a curious reaction. It was said, through email and as gossip, that the epidemic was a sham. That the virus did not exist, or that the epidemic was planned by the current panista government of Mexico (or bye the American government) to influence Election Day on July 5 (or to reactivate world economy).

There were multiple versions of the rumour, but all of them had something in common: it was a way of denying reality. The traumatic experience of those secluded and inactive days, and the economic, but also social and psychological harm they left, created a fertile field for rumours that everything was a complot.

The efficacy of the health authorities was questioned, as well as the science behind their decisions. Today we can see that the epidemic, already spread around the world, is a reality that affects many other countries. Argentina and Chile in their full austral winter, already have 137 and 33 deaths, respectively, and thousands of infected people. Also, Cuba is reporting cases, and the Mexican states of Chiapas, Tabasco and Yucatan have detected an important spike, up to the point that Tabasco has decided to cancel its annual state fair.

In the meantime, research about the virus advances: a group lead by Yoshihiro Kawaoka, from Wisconsin University, reported last Monday on Nature magazine that the swine virus -which is actually a result from mutations and combinations from other already existing viruses, human, bird and swine- causes more harm to the lungs of experimental animals (mice, ferrets and macaques) than the common seasonal influenza virus, and that it can asymptomatically infect pigs (maybe that's why the epidemic was not detected until it jumped into humans).

They also found that people born before 1920 and therefore exposed to the massive epidemic of A/H1N1 influenza in 1918 (spanish flu) have antibodies that can react against the current virus, unlike people born after (thus maybe explaining the anomalous behavior of the epidemic, which affected mainly younger people).

Currently, the virus is still sensitive to tamiflu, but it is very likely that in the short term some resistant varieties will arise. Soon, we will have a vaccine, but it will take time to produce it in enough quantities to respond to the World Health Organization's request for "all countries to have access to the vaccine."

The reality of the pandemic imposes itself, beyond any belief or rumour. The countries should better pay attention to what science reveals, and they should act united in consequence.

(translated by Adrián Robles Benavides)

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Mexican genome, my foot!

by Martín Bonfil Olivera

Published in Milenio Diario, May 20, 2009

On May 12, the "Mexican genome" was presented with a lot of hype.

But according to the National Institute of Genomic Medicine (Inmegen), which did the work, what was really shown was "the map of the genome of Mexicans". This distinction matters because there is no unique genome that we Mexicans all share. Each human being has its own combination of genes. And although the variation between individuals is minimal (0.5 percent), it's what makes us unique.

The media also gave the wrong impression that the "Mexican genome" information was read letter by letter.

Actually, the study titled "Analysis of genomic diversity in Mexican Mestizo populations to develop genomic medicine in Mexico" was much more modest. It examined the differences in little genetic markers between 300 individuals of seven groups: six mestizo and one from Zapotec civilization. It's a smaller version of the so-called "Hap Map", or "haplotype map": the study of genetic markers in different population groups of the world. It will be useful to relate the genetic variability with the susceptibility of the populations to certain diseases (that' where all the talk about "genetic medicine" comes from).

Inmegen concludes that it would be worthy to perform a haplotype map of the Mexican population. The study is the draft of a draft that would allow to start developing genetic medicine in Mexico.

But reading the statements of Felipe Calderón, the de facto president of Mexico ("we are entering the medicine of the third millennium", "we will have first world health", "we could prevent the development of diseases such as cancer, diabetes, hypertension or obesity, etc."), it looks like we were already in the first world.

Reality is different: Inmegen lacks support. It operates in inappropriate facilities - an office building where they cannot work with radioactivity nor microorganisms - and the construction of their definitive building is plagued with irregularities. Until recently, the Institute had a very rigid hierarchical structure in which only its director could make decisions.

And the situation is general: INDRE (the Diagnostic and Epidemiological Reference Institute), fundamental in the influenza epidemic, is "obsolete and insecure", as reported on monday by MILENIO. As published in the first page of El Universal (one of the most influential newspapers in Mexico), "Mexico is paying its abandonment of science".

With all the shortages on the health research system, to simulate that Mexico is a scientific power is dishonest.

(translated by Adrián Robles Benavides)

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Schizophrenia

by Martí­n Bonfil Olivera
Published in Milenio Diario, May 13, 2009

The relationship between Mexicans and science is schizophrenic. On the one side, we want to trust science, and on the other we deny its credibility.

In the wake of the recent outbreak of influenza, Mexican media demanded precise and fixed figures from day one, when the were impossible to have. Reporters demanded them in part by lack or knowledge about how science works, how it advances slowly and by successive approximations.

But the informative void was filled by another virus: conspiracy theories (mainly through e-mails or by word of mouth).

The majority of these were just simply absurd: the virus is an invention ("influenza my ass", López Obrador dixit); Obama brought the virus to Mexico; it was released as part of an agreement to reactivate world economy, at any cost; the outbreak was part of a strategy to scare Mexicans right before the July elections…

The problema is that in Mexico —and in a lot of other Countries— we lack a scientific culture that, beyond having or not certain knowledge, would allow us to distinguish between anecdotes or suppositions and verified data.

What we do have, certainlly, is an advanced "culture of distrust": when our expectations do not match, we deny the data, we accuse science of authoritarism and we tend to believe in complots.

As the eminent mexican pathologist Ruy Pérez Tamayo writes (La Crónica, May 8) "the handling of the necessary measures to face an epidemic is not only matter of logic and good intentions; it deals with actions based on a lot of accumulated experience through the years, on specific and well documented information, on a wisdom acquired in the books as well as in the field. For an emergency situation such as the one Mexico is going through, it is fundamental to trust authorities, especially when these are real experts with regards to the problem".

Unfortunately, our authorities have not earned that trust. Sadly, also, our culture of distrust makes us prefer conspiracy theories than trustful information.

Poor Mexico: so little science and such a taste for rumors!

(translated by Adrián Robles Benavides)

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Virus, science and society

by Martín Bonfil Olivera
Published on Milenio Diario, May 6, 2009

The influenza outbrake that has kept Mexico City - and the whole country - semi-paralyzed since April 24 leaves several points clear.

First, the outbreak was expected. Not necessarily in Mexico, or from viral sub-type H1N1 (the favorite candidate was H5N1 which caused the avian flu outbrake in 2006). But evolution, the nature of these viruses —promiscuity; fragmented genome; human, swine and avian hosts— and the natural history of influenza made it perfectly predictable that sooner or later we would be facing another pandemic.

Second, a problem of this magnitude its not only a scientific or medical matter: it affects the whole of society: economy, politics, diplomacy, daily living (we chilangos, inhabitants of Mexico city, know that well). International organisms (especially the World Health Organization) had the good sense to foresee and prepare measures to contain the inevitable: manuals, international agreements, labs, purchase of anti-viral drugs…

Mexico simply followed these indications —not ideally, but adequately, considering our limitations— when the outbreak data were clear.

Now there's talk of slowness in the response, but one of the bad things about an epidemic outbrake is that it cannot be recognized until it's there. To declare the alert before being sure was too high a risk (there are also those who say that the measures were excessive, but the virus could have been very lethal: H5N1 kills 50% of people infected.)

My usual readers know that I don't support Felipe Calderón, our non-legitimate president. But in this case, the actions of his government, as well as the ones from Marcelo Ebrard's (in Mexico City) were not only appropriate, but successful. The intellectual credit for this is for the international medical community; but the political credit is theirs.

The lessons from this situation are that we have to demand more support for scientific investigation and the reconstruction of a health system that works on prevention and research —not only in health attention. There's also a necessity of a much better communication strategy for authorities. And finally, an urgency to have more well prepared science journalists, to avoid the epidemy of conspiracy theories that only make social reaction much more difficult.

(translated by Adrián Robles Benavides)

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Influenza and evolution

by Martín Bonfil Olivera
Published on Milenio Diario, April 29, 2009

The problem is that's what viruses are like: promiscuous and addicted to gambling. And that's what evolution is like, taking species trough twisted and unexpected roads. And that's what science is like, unable to advance on its own road, no less random, faster than it can, held up by its method, which demands it makes sure about what it knows up to that moment before taking the next step.

The influenza virus which is currently bothering us (family orthomyxoviridae, type A, the most common ones, that also infect birds, pigs and horses) is, as are all viruses, a protein capsule that contains genetic material; in this case, ribonucleic acid (RNA), the older and less stable cousin of DNA.That's part of the problem: RNA copying is less accurate: sometimes it adds, sometimes it substracts, and thus causes spontaneous mutations inside one species of viruses.

And if several different viruses infect one same cell, they can recombine, taking with them pieces of genetic information from the others. The virus that concerns us has genes from other influenza viruses that infect humans, pigs and birds. And it can continue changing. What's alarming is the fact that it has learned to jump from human to human (as was feared from bird flue in 2006).

Its last name H1N1 refers to two proteins of its surface: haemaglutinin (of which there are 15 variants; this is number 1), which the virus uses to bind to the cell it's going to infect, and neuraminidase (9 variants) which allow the new viral particles to come out of the infected cell without being stuck to it.

Oseltamivir (Tamiflu -do not self medicate!), one of the drugs that work against the current influenza virus, inhibits this enzyme, and prevents that the new viruses form disseminating.

Science, as evolution, is unpredictable. I can seem slow and expensive, but if James Watson and Francis Crick hadn’t discovered, 56 years ago, the DNA double helix, today we wouldn't have the molecular biology tools that allow us to study and fight this virus.

And if we do not widely invest in scientific investigation —as Barack Obama said, immediately backing his words by increasing his country's investing in science by 3 percent of USA's gross domestic product— we won't be able to fight future crises -whether they be health crises or any other type of crises.

(translated by Adrián Robles Benavides)

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