Arquivo da tag: Genética

New DNA Analysis Shows Ancient Humans Interbred with Denisovans (Scientific American)

A new high-coverage DNA sequencing method reconstructs the full genome of Denisovans–relatives to both Neandertals and humans–from genetic fragments in a single finger bone

By Katherine Harmon  | Thursday, August 30, 2012

denisovan genome finger boneFRAGMENT OF A FINGER: This replica of the Denisovan finger bone shows just how small of a sample the researchers had to extract DNA from.Image: Image courtesy of Max Planck Institute for Evolutionary Anthropology

Tens of thousands of years ago modern humans crossed paths with the group of hominins known as the Neandertals. Researchers now think they also met another, less-known group called the Denisovans. The only trace that we have found, however, is a single finger bone and two teeth, but those fragments have been enough to cradle wisps of Denisovan DNA across thousands of years inside a Siberian cave. Now a team of scientists has been able to reconstruct their entire genome from these meager fragments. The analysis adds new twists to prevailing notions about archaic human history.

“Denisova is a big surprise,” says John Hawks, a biological anthropologist at the University of Wisconsin–Madison who was not involved in the new research. On its own, a simple finger bone in a cave would have been assumed to belong to a human, Neandertal or other hominin. But when researchers first sequenced a small section of DNA in 2010—a section that covered about 1.9 percent of the genome—they were able to tell that the specimen was neither. “It was the first time a new group of distinct humans was discovered” via genetic analysis rather than by anatomical description, said Svante Pääbo, a researcher at the Max Planck Institute (M.P.I.) for Evolutionary Anthropology in Germany, in a conference call with reporters.

Now Pääbo and his colleagues have devised a new method of genetic analysis that allowed them to reconstruct the entire Denisovan genome with nearly all of the genome sequenced approximately 30 times over akin to what we can do for modern humans. Within this genome, researchers have found clues into not only this group of mysterious hominins, but also our own evolutionary past. Denisovans appear to have been more closely related to Neandertals than to humans, but the evidence also suggests that Denisovans and humans interbred. The new analysis also suggests new ways that early humans may have spread across the globe. The findings were published online August 30 in Science.

Who were the Denisovans?
Unfortunately, the Denisovan genome doesn’t provide many more clues about what this hominin looked like than a pinky bone does. The researchers will only conclude that Denisovans likely had dark skin. They also note that there are alleles “consistent” with those known to call for brown hair and brown eyes. Other than that, they cannot say.

Yet the new genetic analysis does support the hypothesis that Neandertals and Denisovans were more closely related to one another than either was to modern humans. The analysis suggests that the modern human line diverged from what would become the Denisovan line as long as 700,000 years ago—but possibly as recently as 170,000 years ago.

Denisovans also interbred with ancient modern humans, according to Pääbo and his team. Even though the sole fossil specimen was found in the mountains of Siberia, contemporary humans from Melanesia (a region in the South Pacific) seem to be the most likely to harbor Denisovan DNA. The researchers estimate that some 6 percent of contemporary Papuans’ genomes come from Denisovans. Australian aborigines and those from Southeast Asian islands also have traces of Denisovan DNA. This suggests that the two groups might have crossed paths in central Asia and then the modern humans continued on to colonize the islands of Oceania.

Yet contemporary residents of mainland Asia do not seem to posses Denisovian traces in their DNA, a “very curious” fact, Hawks says. “We’re looking at a very interesting population scenario”—one that does not jibe entirely with what we thought we knew about how waves modern human populations migrated into and through Asia and out to Oceania’s islands. This new genetic evidence might indicate that perhaps an early wave of humans moved through Asia, mixed with Denisovans and then relocated to the islands—to be replaced in Asia by later waves of human migrants from Africa. “It’s not totally obvious that that works really well with what we know about the diversity of Asians and Australians,” Hawks says. But further genetic analysis and study should help to clarify these early migrations.

Just as with modern Homo sapiens, the genome of a single individual cannot tell us exactly what genes and traits are specific to all Denisovans. Yet, just one genome can reveal the genetic diversity of an entire population. Each of our genomes contains information about generations far beyond those of our parents and grandparents, said David Reich, a researcher at the Massachusetts Institute of Technology–Harvard University Broad Institute and a co-author on the paper. Scientists can compare and contrast the set of genes on each chromosome—passed down from each parent—and extrapolate this process back through the generations. “You contain a multitude of ancestors within you,” Reich said, borrowing from Walt Whitman.

The new research reveals that the Denisovans had low genetic diversity—just 26 to 33 percent of the genetic diversity of contemporary European or Asian populations. And for the Denisovans, the population on the whole seems to have been very small for hundreds of thousands of years, with relatively little genetic diversity throughout their history.

Curiously, the researchers noted in their paper, the Denisovan population shows “a drastic decline in size at the time when the modern human population began to expand.”

Why were modern humans so successful whereas Denisovans (and Neandertals) went extinct? Pääbo and his co-authors could not resist looking into the genetic factors that might be at work. Some of the key differences, they note, center around brain development and synaptic connectivity. “It makes sense that what pops up is connectivity in the brain,” Pääbo noted. Neandertals had a similar brain size–to-body ratio as we do, so rather than cranial capacity, it might have been underlying neurological differences that could explain why we flourished while they died out, he said.

Hawks counters that it might be a little early to begin drawing conclusions about human brain evolution from genetic comparisons with archaic relatives. Decoding the genetic map of the brain and cognition from a genome is still a long way off, he notes—unraveling skin color is still difficult enough given our current technologies and knowledge.

New sequencing for old DNA
The Denisovan results rely on a new method of genetic analysis developed by paper co-author Matthias Meyer, also of M.P.I. The procedure allows the researchers to sequence the full genome by using single strands of genetic material rather than the typical double strands required. The technique, which they are calling a single-stranded library preparation, involves stripping the genetic material down to individual strands to copy and avoids a purification step, which can lose precious genetic material.

The finger bone—just one disklike phalanx—is so small that it does not contain enough usable carbon for dating, the researchers note. But by counting the number of genetic mutations in a genome and comparing them with other living relatives, such as modern humans and chimpanzees, given assumed rates of mutations since breaking with a last common ancestor, “for the first time you can try to estimate this number into a date and provide molecular dating of the fossil,” Meyer said. With the new resolution, the researchers estimate the age of the bone to 74,000 to 82,000 years ago. But that is a wide window, and previous archaeological estimates for the bone are a bit younger, ranging from 30,000 to 50,000 years old. These genetic estimations are also still in limbo because of ongoing debate about the average rate of genetic mutations over time, which could skew the age. “Nevertheless,” the researchers noted in their paper, “the results suggest that in the future it will be possible to determine dates of fossils based on genome sequences.”

This new sequencing approach can be used for any DNA that is too fragmented to be read well through more traditional methods. Meyer noted that it could come in handy for analysis of both ancient DNA and contemporary forensic evidence, which also often contains only fragments of genetic material.

Hawks is excited about the new sequencing technology. It is also helpful to have a technology developed specifically for the evolutionary field, he notes. “We’re always using the new techniques from other fields, and this is a case where the new technique is developed just for this.”

Hawks himself has heard from the researchers that have worked with the Denisovan samples that “the Denisovan pinky is just extraordinary” in terms of the amount of DNA preserved in it. Most bone fragments would be expected to contain less than 5 percent of the individual’s endogenous DNA, but this fortuitous finger had a surprising 70 percent, the researchers noted in the study. And many Neandertal fragments have been preserved in vastly different states—many are far worse off than this Denisovan finger bone.

The new sequencing approach could also improve our understanding of known specimens and the evolutionary landscape as a whole. “It’s going to increase the yield from other fossils,” Hawks notes. Many of the Neandertal specimens, for example, have only a small fraction of their genome sequenced. “If we can go from 2 percent to the whole genome, that opens up a lot more,” Hawks says. “Going back further in time will be exciting,” he notes, and this new technique should allow us to do that. “There’s a huge race on—it’s exciting.”

The Denisovans might be the first non-Neandertal archaic human to be sequenced, but they are likely not going to be the last. The researchers behind this new study are already at work using the new single-strand sequencing technique to reexamine older specimens. (Meyer said they were working on reassessing old samples but would not specify which specimens they were studying—the mysterious “hobbit” H. floresiensis would be a worthy candidate.) Pääbo suggests Asia as a particularly promising location to look for other Denisovan-like groups. “I would be surprised if there were not other groups to be found there in the future,” he said.

Taking this technique to specimens from Africa is also likely to yield some exciting results, Hawks says. Africa, with its rich human evolutionary history, holds the greatest genetic diversity. The genomes of contemporary pygmy and hunter–gatherer tribes in Africa, for example, have roughly as many differences as do those of European modern humans and Neandertals. So “any ancient specimen that we find in Africa might be as different from us as Neandertals,” Hawks says. “Anything we find from the right place might be another Denisovan.”

Gene That Predicts Happiness in Women Discovered (Science Daily)

ScienceDaily (Aug. 28, 2012) — A new study has found a gene that appears to make women happy, but it doesn’t work for men. The finding may help explain why women are often happier than men, the research team said.

A new study has found a gene that appears to make women happy, but it doesn’t work for men. The finding may help explain why women are often happier than men. (Credit: © Yuri Arcurs / Fotolia)

Scientists at the University of South Florida (USF), the National Institutes of Health (NIH), Columbia University and the New York State Psychiatric Institute reported that the low-expression form of the gene monoamine oxidase A (MAOA) is associated with higher self-reported happiness in women. No such association was found in men.

The findings appear online in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry.

“This is the first happiness gene for women,” said lead author Henian Chen, MD, PhD, associate professor in the Department of Epidemiology and Biostatistics, USF College of Public Health.

“I was surprised by the result, because low expression of MAOA has been related to some negative outcomes like alcoholism, aggressiveness and antisocial behavior,” said Chen, who directs the Biostatistics Core at the USF Health Morsani College of Medicine’s Clinical and Translational Sciences Institute. “It’s even called the warrior gene by some scientists, but, at least for women, our study points to a brighter side of this gene.”

While they experience higher rates of mood and anxiety disorders, women tend to report greater overall life happiness than do men. The reason for this remains unclear, Chen said. “This new finding may help us to explain the gender difference and provide more insight into the link between specific genes and human happiness.”

The MAOA gene regulates the activity of an enzyme that breaks down serontin, dopamine and other neurotransmitters in the brain — the same “feel-good” chemicals targeted by many antidepressants. The low-expression version of the MAOA gene promotes higher levels of monoamine, which allows larger amounts of these neurotransmitters to stay in the brain and boost mood.

The researchers analyzed data from a population-based sample of 345 individuals — 193 women and 152 men — participating in Children in the Community, a longitudinal mental health study. The DNA of study subjects had been analyzed for MAOA gene variation and their self-reported happiness was scored by a widely used and validated scale.

After controlling for various factors, ranging from age and education to income, the researchers found that women with the low-expression type of MAOA were significantly happier than others. Compared to women with no copies of the low-expression version of the MAOA gene, women with one copy scored higher on the happiness scale and those with two copies increased their score even more.

While a substantial number of men carried a copy of the “happy” version of the MAOA gene, they reported no more happiness than those without it.

So, why the genetic gender gap in feeling good?

The researchers suspect the difference may be explained in part by the hormone testosterone, found in much smaller amounts in women than in men. Chen and his co-authors suggest that testosterone may cancel out the positive effect of MAOA on happiness in men.

The potential benefit of MAOA in boys could wane as testosterone levels rise with puberty, Chen said. “Maybe men are happier before adolescence because their testosterone levels are lower.”

Chen emphasizes that more research is needed to identify which specific genes influence resilience and subjective well-being, especially since studies of twins estimate genetic factors account for 35 to 50 percent of the variance in human happiness.

While happiness is not determined by a single gene, there is likely a set of genes that, along with life experiences, shape our individual happiness levels, Chen said. “I think the time is right for more genetic studies that focus on well-being and happiness.”

“Certainly it could be argued that how well-being is enhanced deserves at least as much attention as how (mental) disorders arise; however, such knowledge remains limited.”

The study by Chen and colleagues was supported by the National Institutes of Health and a USF proposal enhancement grant.

Journal Reference:

  1. Henian Chen, Daniel S. Pine, Monique Ernst, Elena Gorodetsky, Stephanie Kasen, Kathy Gordon, David Goldman, Patricia Cohen. The MAOA gene predicts happiness in womenProgress in Neuro-Psychopharmacology and Biological Psychiatry, 2012; DOI:10.1016/j.pnpbp.2012.07.018

The Role of Genes in Political Behavior (Science Daily)

ScienceDaily (Aug. 27, 2012) — Politics and genetics have traditionally been considered non-overlapping fields, but over the past decade it has become clear that genes can influence political behavior, according to a review published online August 27th in Trends in Genetics. This paradigm shift has led to novel insights into why people vary in their political preferences and could have important implications for public policy.

“We’re seeing an awakening in the social sciences, and the wall that divided politics and genetics is really starting to fall apart,” says review author Peter Hatemi of the University of Sydney. “This is a big advance, because the two fields could inform each other to answer some very complex questions about individual differences in political views.”

In the past, social scientists had assumed that political preferences were shaped by social learning and environmental factors, but recent studies suggest that genes also strongly influence political traits. Twin studies show that genes have some influence on why people differ on political issues such as the death penalty, unemployment and abortion. Because this field of research is relatively new, only a handful of genes have been implicated in political ideology and partisanship, voter turnout, and political violence.

Future research, including gene-expression and sequencing studies, may lead to deeper insights into genetic influences on political views and have a greater impact on public policy. “Making the public aware of how their mind works and affects their political behavior is critically important,” Hatemi says. “This has real implications for the reduction of discrimination, foreign policy, public health, attitude change and many other political issues.”

Journal Reference:

  1. Peter K Hatemi and Rose McDermott. The Genetics of Politics: Discovery, Challenges and ProgressTrends in Genetics, August 27, 2012 DOI: 10.1016/j.tig.2012.07.004

Pai de gêmeos, um negro e outro branco (Extra)

Bruno Cunha

Fonte Extra

Finalmente eles foram reconhecidos no futebol. Enquanto um é zagueiro, tem cabelos crespos e adora doce, o outro é atacante, tem fios louros e prefere salgado. Com as diferenças, ficava difícil perceber que David Evangelista de Oliveira, o branco, e Nícolas, o negro, são irmãos gêmeos.

— Os pais dos coleguinhas do futebol achavam que só um era meu filho e que o outro era um amiguinho dele. E olha que os dois já treinam há um ano e meio. Mas só agora descobriram que são irmãos gêmeos — conta o montador de peças de laboratório Luis Carlos de Oliveira Silva, de 42 anos, pai das crianças.

Fama no bairro

Morador de Campo Grande, Luis tomou um susto quando soube da dupla gravidez da mulher, Audicelia Evangelista, de 45 anos. E outro após o nascimento dos filhos, um negro, como o pai, e outro branco, como a mãe.

— Na época, os colegas brincavam: “ah, esse aí não é seu filho, não!”. Uma vez entrei numa maternidade e o David me chamou de pai. O segurança cochichou: “não é filho dele.” Mas eu penso: os dois puxaram ao pai e à mãe — afirma Luis.

Na porta do quarto, a frase “gêmeos em ação”
Na porta do quarto, a frase “gêmeos em ação” Foto: Nina Lima / Extra

Famosos no sub-bairro Santa Rosa, Nícolas e David, aos 9 anos, já começam a colher os frutos da fama que os levou a um programa de TV ainda recém-nascidos. Outro dia mesmo foram seguidos por duas meninas que descobriram onde moravam.

— Cheguei do trabalho umas 19h30m e peguei o Nícolas passando gel no cabelo e o Davi se arrumando. Logo em seguida, duas meninas gritaram o nome deles aqui no portão. Elas estavam tomando coragem para chamá-los para sair — explica o pai, que se diverte ao saber que os filhos já estão se interessando pelas meninas.

Os gêmeos
Os gêmeos Foto: Acervo pessoal / Divulgação

Estimativa: menos de 1% de chance de incidência

O nascimento de irmãos gêmeos, um negro e outro branco, ainda surpreende. Em 2006, por exemplo, o EXTRA mostrou o caso dos irmãos Pedro e Nathan Henrique Rodrigues, que intrigou Costa Barros.

Um ano depois, o cabeleireiro Carlos Henrique Fonseca, o pai, na época com 26 anos, contou que muitas pessoas ainda estranhavam quando viam Pedro, negro como ele, ao lado de Nathan, branco como mãe, a então frentista Valéria Gomes, de 22 anos.

Diferentes, mas torcem pelo mesmo time
Diferentes, mas torcem pelo mesmo time Foto: Nina Lima / Extra

Miscigenação

A cegonha também foi generosa, em Botafogo, onde vivem as gêmeas Beatriz e Maria Gaia Gerstner, hoje com 8 anos. Uma é morena como a mãe e a outra é branca como o pai, um alemão.

— Quando estou com a branca não acham que é minha filha. E quando o pai está com a morena é a mesma coisa — conta a mãe, Janaína Gaia, de 35 anos, hoje separada do pai delas.

A diretora do Centro Vida — Reprodução Humana Assistida, na Barra, na Zona Oeste, Maria Cecília Erthal, estima que há menos de 1% de chance do nascimento de gêmeos diferentes.

— É a miscigenação que faz com que os genes de pais negros e brancos se encontrem — explica.

*   *   *

Jemima Pompeu enviou o seguinte comentário:

Gêmeos com cores de pele diferentes surpreendem pais, mas não os cientistas. Veja alguns casos no link abaixo:

Nature or nurture? It may depend on where you live (AAAS)

12-Jun-2012

By Craig Brierley

The extent to which our development is affected by nature or nurture – our genetic make-up or our environment – may differ depending on where we live, according to research funded by the Medical Research Council and the Wellcome Trust.

In a study published today in the journal Molecular Psychiatry, researchers from the Twins Early Development Study at King’s College London’s Institute of Psychiatry studied data from over 6,700 families relating to 45 childhood characteristics, from IQ and hyperactivity through to height and weight. They found that genetic and environmental contributions to these characteristics vary geographically in the United Kingdom, and published their results online as a series of nature-nurture maps.

Our development, health and behaviour are determined by complex interactions between our genetic make-up and the environment in which we live. For example, we may carry genes that increase our risk of developing type 2 diabetes, but if we eat a healthy diet and get sufficient exercise, we may not develop the disease. Similarly, someone may carry genes that reduce his or her risk of developing lung cancer, but heavy smoking may still lead to the disease.

The UK-based Twins Early Development Study follows over 13,000 pairs of twins, both identical and non-identical, born between 1994 and 1996. When the twins were age 12, the researchers carried out a broad survey to assess a wide range of cognitive abilities, behavioural (and other) traits, environments and academic achievement in 6,759 twin pairs. The researchers then designed an analysis that reveals the UK’s genetic and environmental hotspots, something which had never been done before.

“These days we’re used to the idea that it’s not a question of nature or nurture; everything, including our behaviour, is a little of both,” explains Dr Oliver Davis, a Sir Henry Wellcome Postdoctoral Fellow at King’s College London’s Institute of Psychiatry. “But when we saw the maps, the first thing that struck us was how much the balance of genes and environments can vary from region to region.”

“Take a trait like classroom behaviour problems. From our maps we can tell that in most of the UK around 60% of the difference between people is explained by genes. However, in the South East genes aren’t as important: they explain less than half of the variation. For classroom behaviour, London is an ‘environmental hotspot’.”

The maps give the researchers a global overview of how the environment interacts with our genomes, without homing in on particular genes or environments. However, the patterns have given them important clues about which environments to explore in more detail.

“The nature-nurture maps help us to spot patterns in the complex data, and to try to work out what’s causing these patterns,” says Dr Davis. “For our classroom behaviour example, we realised that one thing that varies more in London is household income. When we compare maps of income inequality to our nature-nurture map for classroom behaviour, we find income inequality may account for some of the pattern.

“Of course, this is just one example. There are any number of environments that vary geographically in the UK, from social environments like health care or education provision to physical environments like altitude, the weather or pollution. Our approach is all about tracking down those environments that you wouldn’t necessarily think of at first.”

It may be relatively easy to explain environmental hotspots, but what about the genetic hotspots that appear on the maps: do people’s genomes vary more in those regions? The researchers believe this is not the case; rather, genetic hotspots are areas where the environment exposes the effects of genetic variation.

For example, researchers searching for gene variants that increase the risk of hay fever may study populations from two regions. In the first region people live among fields of wind-pollinated crops, whereas the second region is miles away from those fields. In this second region, where no one is exposed to pollen, no one develops hay fever; hence any genetic differences between people living in this region would be invisible.

On the other hand, in the first region, where people live among the fields of crops, they will all be exposed to pollen and differences between the people with a genetic susceptibility to hay fever and the people without will stand out. That would make the region a genetic hotspot for hay fever.

“The message that these maps really drive home is that your genes aren’t your destiny. There are plenty of things that can affect how your particular human genome expresses itself, and one of those things is where you grow up,” says Dr Davis.

Hope, Hype and Genetic Breakthroughs (Wall Street Journal)

By CARL ZIMMER

I talk to scientists for a living, and one of my most memorable conversations took place a couple of years ago with an engineer who put electrodes in bird brains. The electrodes were implanted into the song-generating region of the brain, and he could control them with a wireless remote. When he pressed a button, a bird singing in a cage across the lab would fall silent. Press again, and it would resume its song.

I could instantly see a future in which this technology brought happiness to millions of people. Imagine a girl blind from birth. You could implant a future version of these wireless electrodes in the back of her brain and then feed it images from a video camera.

As a journalist, I tried to get the engineer to explore what seemed to me to be the inevitable benefits of his research. To his great credit, he wouldn’t. He wasn’t even sure his design would ever see the inside of a human skull. There were just too many ways for it to go wrong. He wanted to be very sure that I understood that and that I wouldn’t claim otherwise. “False hope,” he warned me, “is a sinful thing.”

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Stephen Voss. Gene therapy allowed this once-blind dog to see again.

Over the past two centuries, medical research has yielded some awesome treatments: smallpox wiped out with vaccines, deadly bacteria thwarted by antibiotics, face transplants. But when we look back across history, we forget the many years of failure and struggle behind each of these advances.

This foreshortened view distorts our expectations for research taking place today. We want to believe that every successful experiment means that another grand victory is weeks away. Big stories appear in the press about the next big thing. And then, as the years pass, the next big thing often fails to materialize. We are left with false hope, and the next big thing gets a reputation as the next big lie.

In 1995, a business analyst named Jackie Fenn captured this intellectual whiplash in a simple graph. Again and again, she had seen new advances burst on the scene and generate ridiculous excitement. Eventually they would reach what she dubbed the Peak of Inflated Expectations. Unable to satisfy their promise fast enough, many of them plunged into the Trough of Disillusionment. Their fall didn’t necessarily mean that these technologies were failures. The successful ones slowly emerged again and climbed the Slope of Enlightenment.

When Ms. Fenn drew the Hype Cycle, she had in mind dot-com-bubble technologies like cellphones and broadband. Yet it’s a good model for medical advances too. I could point to many examples of the medical hype cycle, but it’s hard to think of a better one than the subject of Ricki Lewis’s well-researched new book, “The Forever Fix”: gene therapy.

The concept of gene therapy is beguilingly simple. Many devastating disorders are the result of mutant genes. The disease phenylketonuria, for example, is caused by a mutation to a gene involved in breaking down a molecule called phenylalanine. The phenylalanine builds up in the bloodstream, causing brain damage. One solution is to eat a low-phenylalanine diet for your entire life. A much more appealing alternative would be to somehow fix the broken gene, restoring a person’s metabolism to normal.

In “The Forever Fix,” Ms. Lewis chronicles gene therapy’s climb toward the Peak of Inflated Expectations over the course of the 1990s. A geneticist and the author of a widely used textbook, she demonstrates a mastery of the history, even if her narrative sometimes meanders and becomes burdened by clichés. She explains how scientists learned how to identify the particular genes behind genetic disorders. They figured out how to load genes into viruses and then to use those viruses to insert the genes into human cells.

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Stephen Voss. Alisha Bacoccini is tested on her ability to read letters, at UPenn Hospital, in Philadelphia, PA on Monday, June 23, 2008. Bacoccini is undergoing an experimental gene therapy trial to improve her sight.

By 1999, scientists had enjoyed some promising successes treating people—removing white blood cells from leukemia patients, for example, inserting working genes, and then returning the cells to their bodies. Gene therapy seemed as if it was on the verge of becoming standard medical practice. “Within the next decade, there will be an exponential increase in the use of gene therapy,” Helen M. Blau, the then-director of the gene-therapy technology program at Stanford University, told Business Week.

Within a few weeks of Ms. Blau’s promise, however, gene therapy started falling straight into the Trough. An 18-year-old man named Jesse Gelsinger who suffered from a metabolic disorder had enrolled in a gene-therapy trial. University of Pennsylvania scientists loaded a virus with a working version of an enzyme he needed and injected it into his body. The virus triggered an overwhelming reaction from his immune system and within four days Gelsinger was dead.

Gene therapy nearly came to a halt after his death. An investigation revealed errors and oversights in the design of Gelsinger’s trial. The breathless articles disappeared. Fortunately, research did not stop altogether. Scientists developed new ways of delivering genes without triggering fatal side effects. And they directed their efforts at one part of the body in particular: the eye. The eye is so delicate that inflammation could destroy it. As a result, it has evolved physical barriers that keep the body’s regular immune cells out, as well as a separate battalion of immune cells that are more cautious in their handling of infection.

It occurred to a number of gene-therapy researchers that they could try to treat genetic vision disorders with a very low risk of triggering horrendous side effects of the sort that had claimed Gelsinger’s life. If they injected genes into the eye, they would be unlikely to produce a devastating immune reaction, and any harmful effects would not be able to spread to the rest of the body.

Their hunch paid off. In 2009 scientists reported their first success with gene therapy for a congenital disorder. They treated a rare form of blindness known as Leber’s congenital amaurosis. Children who were once blind can now see.

As “The Forever Fix” shows, gene therapy is now starting its climb up the Slope of Enlightenment. Hundreds of clinical trials are under way to see if gene therapy can treat other diseases, both in and beyond the eye. It still costs a million dollars a patient, but that cost is likely to fall. It’s not yet clear how many other diseases gene therapy will help or how much it will help them, but it is clearly not a false hope.

Gene therapy produced so much excitement because it appealed to the popular idea that genes are software for our bodies. The metaphor only goes so far, though. DNA does not float in isolation. It is intricately wound around spool-like proteins called histones. It is studded with caps made of carbon, hydrogen and oxygen atoms, known as methyl groups. This coiling and capping of DNA allows individual genes to be turned on and off during our lifetimes.

The study of this extra layer of control on our genes is known as epigenetics. In “The Epigenetics Revolution,” molecular biologist Nessa Carey offers an enlightening introduction to what scientists have learned in the past decade about those caps and coils. While she delves into a fair amount of biological detail, she writes clearly and compellingly. As Ms. Carey explains, we depend for our very existence as functioning humans on epigenetics. We begin life as blobs of undifferentiated cells, but epigenetic changes allow some cells to become neurons, others muscle cells and so on.

Epigenetics also plays an important role in many diseases. In cancer cells, genes that are normally only active in embryos can reawaken after decades of slumber. A number of brain disorders, such as autism and schizophrenia, appear to involve the faulty epigenetic programming of genes in neurons.

Scientists got their first inklings about epigenetics decades ago, but in the past few years the field has become hot. In 2008 the National Institutes of Health pledged $190 million to map the epigenetic “marks” on the human genome. New biotech start-ups are trying to carry epigenetic discoveries into the doctor’s office. The FDA has approved cancer drugs that alter the pattern of caps on tumor-cell DNA. Some studies on mice hint that it may be possible to treat depression by taking a pill that adjusts the coils of DNA in neurons.

People seem to be getting giddy about the power of epigenetics in the same way they got giddy about gene therapy in the 1990s. No longer is our destiny written in our DNA: It can be completely overwritten with epigenetics. The excitement is moving far ahead of what the science warrants—or can ever deliver. Last June, an article on the Huffington Post eagerly seized on epigenetics, woefully mangling two biological facts: one, that experiences can alter the epigenetic patterns in the brain; and two, that sometimes epigenetic patterns can be passed down from parents to offspring. The article made a ridiculous leap to claim that we can use meditation to change our own brains and the brains of our children—and thereby alter the course of evolution: “We can jump-start evolution and leverage it on our own terms. We can literally rewire our brains toward greater compassion and cooperation.” You couldn’t ask for a better sign that epigenetics is climbing the Peak of Inflated Expectations at top speed.

The title “The Epigenetics Revolution” unfortunately adds to this unmoored excitement, but in Ms. Carey’s defense, the book itself is careful and measured. Still, epigenetics will probably be plunging soon into the Trough of Disillusionment. It will take years to see whether we can really improve our health with epigenetics or whether this hope will prove to be a false one.

The Forever Fix

By Ricki LewisSt. Martin’s, 323 pages, $25.99

The Epigenetics Revolution

By Nessa CareyColumbia, 339 pages, $26.95

—Mr. Zimmer’s books include “A Planet of Viruses and Evolution: Making Sense of Life,” co-authored with Doug Emlen, to be published in July.

Risco é coisa séria (JC)

JC e-mail 4364, de 14 de Outubro de 2011.

Artigo de Francisco G. Nóbrega enviado ao JC Email pelo autor.

A sociedade moderna está banhada em comunicação. Como “boa notícia não é notícia”, a lente psicológica humana registra sempre um cenário pior que a realidade. A percepção usual é que os riscos de todos os tipos aumentam dia a dia. A redução global da violência, por exemplo, é tema do livro recente do psicólogo da Universidade Harvard, Steven Pinker (http://www.samharris.org/blog/item/qa-with-steven-pinker). Ao arrepio do senso comum, ele demonstra, objetivamente, que estamos progredindo neste quesito.

Mas nossa mente não descança em sua aguda capacidade de detectar outras fontes de risco. Temos alguns campeões de audiência: energia nuclear para eletricidade, alimentos geneticamente modificados e aquecimento global catastrófico e antropogênico. O dano potencial das três ameaças mencionadas, objetivamente, não se concretizou de maneira alguma, embora a terceira ameaça deva se realizar no futuro, segundo seus defensores. As pessoas se encantam com o automóvel e seus acessórios, cada vez mais atraentes. Não se pensa em baní-lo, apesar de resultar em cerca de 40.000 mortos e inúmeros incapacitados cada ano, só no Brasil. David Ropeik, que pertence ao Centro Harvard para Análise de Risco, explica como facilmente se distorce o perigo real de situações. Quanto mais afastadas do senso comum (como radiação e plantas geneticamente modificadas), mais facilmente são manipuladas, por ignorância ou interesses outros, apavorando o cidadão comum. Ropeik explica como este medo sem sentido passa a ser um fator de estresse e um risco objetivo para a saúde das pessoas, devendo ser evitado.

Dentro desse universo, são justificadas as preocupações do Dr. Ferraz (“O feijão nosso de cada dia”, Jornal da Ciência, 6/10/2011). Ele é membro da CTNBio, atua na setorial vegetal/ambiental e sua área de concentração é em agroecologia, o que explica, pelo menos em parte, suas dúvidas. No entanto essas preocupações não têm a consistência sugerida pelo autor e a análise da CTNBio, que resultou na aprovação deste feijão, é confiável.

A comissão se pauta sempre pelas diretivas da legislação que são amplas, para dar conta de todas as possibilidades de risco para os consumidores e meio ambiente. No entanto o corpo técnico existe exatamente para atuar de maneira seletiva e consciente, examinando caso a caso. Os testes são examinadas com o rigor que a modificação introduzida na planta exige para plena segurança. Se as modificações são consideradas sem qualquer risco significativo, os testes são avaliados à luz deste fato.

Testes com muitos animais, altamente confiáveis estatisticamente, seriam exigidos pela comissão na eventualidade de uma planta transgênica produzir, por exemplo, uma molécula pesticida não protéica que seria em tudo semelhante a uma droga produzida pela indústria farmacêutica. Isto poderá acontecer em certo momento, já que as plantas têm capacidade de produzir os mais variados pesticidas naturais para se defenderem na natureza. A substância seria absorvida no intestino e se disseminaria por órgãos e tecidos, possivelmente exercendo efeitos sistêmicos e localizados que exigem avaliação. Isso já aconteceu, sem querer, com uma batata produzida por melhoramento convencional nos EUA. Seu consumo levou a mal estar e foi recolhida apressadamente: portava altos níveis de glicoalcalóides tóxicos para o homem, o que explicava sua excelente resistência às pragas da cultura.

No caso do feijão Embrapa, nenhuma molécula não protéica nova é produzida e o pequeno RNA que interfere com a replicação do vírus, caso alguém venha a ingerir folhas e caules, será um entre centenas ou milhares de RNAs que ingerimos diariamente com qualquer produto vegetal. O RNA introduzido, no entanto, não foi detectado no grão do feijão cozido, usando técnicas extremamente poderosas.

As variações detectadas, se estatisticamente significativas (concentração de vitamina B2 ou cisteína por exemplo) não representam risco algum. A técnica clássica de cultura de tecidos, usada para gerar variedades de qualidade em horticultura e propagação de árvores, reconhecidamente resulta em variações naturais que introduzem certas modificações desejáveis e algumas indesejáveis, que o melhorista depois seleciona. É a variação somaclonal, que também afeta os clones geneticamente modificados na sua fase de seleção.

Portanto, é no mínimo ingênuo dizer que o feijão Embrapa 5.1 “deveria ser idêntico” a variedade de origem pois as manipulações necessárias para gerar o transgênico resultam em certas alterações que, se irrelevantes, são ignoradas e se deletérias são descartadas pelos cientistas. Se fizermos as mesmas análises, cujos resultados preocupam alguns, com as muitas variedades convencionais consumidas no país, as diferenças serão impressionantes e irrelevantes para a questão “segurança”.

Como já foi comentado anteriormente, não existe base factual (bioquímica ou genética) para imaginar que o feijão Embrapa apresente risco maior do que um feijão comum ou melhorado por mutagênese química ou física, que por sinal, não é supervisionado nutricional e molecularmente antes de sua comercialização. Sem base biológica, os testes tornam-se formalidades supérfluas e o ruído experimental, principalmente com amostras pequenas, quase inevitavelmente vai gerar resultados que são irrelavantes a menos que se amplie muito o número de animais (para amostras controle e transgênicas) além de ser prudente incluir animais alimentados com outros feijões convencionais para uma idéia realista do significado das variações detectadas. Imaginem o custo dessa busca “caça fantasma”, desencadeada simplesmente devido a uma aplicação pouco esclarecida do princípio da precaução. As preocupações sem base racional, levantadas a todo momento pelos que temem a tecnologia, se aplicariam com maior lógica aos produtos convencionais.

Caso isso aconteça, do dia para a noite estaria inviabilizada a produção agrícola do planeta. Por que não fazer estudos com Rhizobium e nodulação em todos os feijões comercializados? Por que não conduzir estudos nutricionais de longo prazo com os alimentos convencionais derivados de mutagênese? Qual a razão lógica que exclui essas preocupações com as plantas convencionais? Ou a razão seria metafísica? A alteração introduzida seria “contra a natureza”, algo como o pecado original, que, em muitas interpretações, consistiu apenas em comer o fruto da “árvore do conhecimento”? Recentemente 41 cientistas suecos da área vegetal lançaram um manifesto contra a sobre-regulação da genética moderna na Europa (reproduzido no blog GenPeace: genpeace.blogspot.com). Os autores observam que, fazendo um paralelo com as exigências para os produtos farmacêuticos, a “lógica da legislação atual sugere que apenas drogas produzidas por meio de engenharia genética deveriam ser avaliadas quando a efeitos indesejáveis”.

Instilar o medo com base em suposições não ajuda a proteger a população ou o meio ambiente. Marie Curie teria dito “Na vida nada deve ser temido. Mas tudo deve ser compreendido”. Considero irresponsável usar o “princípio da precaução” como alguns o fazem. Inclusive a OMS caiu nesta armadilha, classificando os telefones celulares no grupo 2B de risco para causar câncer. A radiação destes equipamentos é cerca de um milhão de vezes inferior à energia que pode produzir radicais livres e gerar dano ao DNA. A classe 2B inclui o risco de câncer relativo ao café, resíduos da queima de combustíveis fósseis e uso de dentadura…. O que a WHO manteve viva, irresponsavelmente, é a justificativa para a dúvida, que vai legitimar pesquisas caras e irrelevantes, cujo resultado será inconclusivo, como o mega estudo anterior. Incrivelmente mais perigoso é o uso do celular enquanto se dirige.

Francisco G. da Nóbrega é professor da Universidade de São Paulo (USP).

Genes, germs and the origins of politics (New Scientist)

NS 2813: Genes, germs and the origins of politics

* 18 May 2011 by Jim Giles

A controversial new theory claims fear of infection makes the difference between democracy and dictatorship

COMPARE these histories. In Britain, democracy evolved steadily over hundreds of years. During the same period, people living in what is now Somalia had many rulers, but almost all deprived them of the chance to vote. It’s easy to find other stark contrasts. Citizens of the United States can trace their right to vote back to the end of the 18th century. In Syria, many citizens cannot trace their democratic rights anywhere – they are still waiting for the chance to take part in a meaningful election.

Conventional explanations for the existence of such contrasting political regimes involve factors such as history, geography, and the economic circumstances and culture of the people concerned, to name just a few. But the evolutionary biologist Randy Thornhill has a different idea. He says that the nature of the political system that holds sway in a particular country – whether it is a repressive dictatorship or a liberal democracy – may be determined in large part by a single factor: the prevalence of infectious disease.

It’s an idea that many people will find outrageously simplistic. How can something as complex as political culture be explained by just one environmental factor? Yet nobody has managed to debunk it, and its proponents are coming up with a steady flow of evidence in its favour. “It’s rather astonishing, and it could be true,” says Carlos Navarrete, a psychologist at the Michigan State University in East
Lansing.

Thornhill is no stranger to controversy, having previously co-authored A Natural History of Rape, a book proposing an evolutionary basis for rape. His iconoclastic theory linking disease to politics was inspired in part by observations of how an animal’s development and behaviour can respond rapidly to physical dangers in a region, often in unexpected ways. Creatures at high risk of being eaten by predators, for example, often reach sexual maturity at a younger age than genetically similar creatures in a safer environment, and are more likely to breed earlier in their lives. Thornhill wondered whether threats to human lives might have similarly influential consequences to our psychology.

The result is a hypothesis known as the parasite-stress model, which Thornhill developed at the University of New Mexico, Albuquerque, with his colleague Corey Fincher.

 

 

Xenophobic instincts

The starting point for Thornhill and Fincher’s thinking is a basic human survival instinct: the desire to avoid illness. In a region where disease is rife, they argue, fear of contagion may cause people to avoid outsiders, who may be carrying a strain of infection to which they have no immunity. Such a mindset would tend to make a community as a whole xenophobic, and might also discourage interaction between the various groups within a society – the social classes, for instance – to prevent unnecessary contact that might spread disease. What is more, Thornhill and Fincher argue, it could encourage people to conform to social norms and to respect authority, since adventurous behaviour may flout rules of conduct set in place to prevent contamination.

Taken together, these attitudes would discourage the rich and influential from sharing their wealth and power with those around them, and inhibit the rest of the population from going against the status quo and questioning the authority of those above them. This is clearly not a situation conducive to democracy. When the threat of disease eases, however, these influences no longer hold sway, allowing forces that favour a more democratic social order to come to the fore.

That’s the idea, anyway. But where is the evidence?

The team had some initial support from earlier studies that had explored how a fear of disease affects individual attitudes. In 2006, for example, Navarrete found that when people are prompted to think about disgusting objects, such as spoilt food, they become more likely to express nationalistic values and show a greater distrust of foreigners (Evolution and Human Behavior, vol 27, p 270). More recently, a team from Arizona State University in Tempe found that reading about contagious illnesses made people less adventurous and open to new experiences, suggesting that they have become more inward looking and conformist (Psychological Science, vol 21, p 440).

Temporarily shifting individual opinions is one thing, but Thornhill and Fincher needed to show that these same biases could change the social outlook of a whole society. Their starting point for doing so was a description of cultural attitudes called the “collectivist-individualist” scale. At one end of this scale lies the collectivist outlook, in which people place the overall good of society ahead of the freedom of action of the individuals within it. Collectivist societies are often, though not exclusively, characterised by a greater respect for authority – if it’s seen as being necessary for the greater good. They also tend to be xenophobic and conformist. At the other end there is the individualist viewpoint, which has more emphasis on openness and freedom for the individual.

Pathogen peril

In 2008, the duo teamed up with Damian Murray and Mark Schaller of the University of British  Columbia in Vancouver, Canada, to test the idea that societies with more pathogens would be more collectivist. They rated people in 98 different nations and regions, from Estonia  to Ecuador, on the collectivist-individualist scale, using data from questionnaires and studies of linguistic cues that can betray a social outlook. Sure enough, they saw a correlation: the greater the threat of disease in a region, the more collectivist people’s attitudes were (Proceedings of the Royal Society B, vol 275, p 1279). The correlation remained even when they controlled for potential confounding factors, such as wealth and urbanisation.

A study soon followed showing similar patterns when comparing US states. In another paper, Murray and Schaller examined a different set of data and showed that cultural differences in one collectivist trait – conformity – correlate strongly with disease prevalence (Personality and Social Psychology Bulletin, vol 37, p 318).

Thornhill and Fincher’s next challenge was to find evidence linking disease prevalence not just with cultural attitudes but with the political systems they expected would go with them. To do so, they used a 66-point scale of pathogen prevalence, based on data assembled by the Global Infectious Diseases and Epidemiology Online Network. They then compared their data set with indicators that assess the politics of a country. Democracy is a tough concept to quantify, so the team looked at a few different measures, including the Freedom House Survey, which is based on the subjective judgements of a team of political scientists working for an independent American think tank, and the Index of Democratization, which is based on estimates of voter participation (measured by how much of a population cast their votes and the number of referendums offered to a population) and the amount of competition between political parties.

The team’s results, published in 2009, showed that each measure varied strongly with pathogen prevalence, just as their model predicted (Biological Reviews, vol 84, p 113). For example, when considering disease prevalence, Somalia is 22nd on the list of nations, while the UK comes in 177th. The two countries come out at opposite ends of the democratic scale (see “An infectious idea”).

Importantly, the relationship still holds when you look at historical records of pathogen prevalence. This, together with those early psychological studies of immediate reactions to disease, suggests it is a nation’s health driving its political landscape, and not the other way around, according to the team.

Last year, they published a second paper that used more detailed data of the diseases prevalent in each region. They again found that measures of collectivism and democracy correlate with the presence of diseases that are passed from human to human – though not with the prevalence of diseases transmitted directly from animals to humans, like rabies (Evolutionary Psychology, vol 8, p 151). Since collectivist behaviours would be less important for preventing such infections, this finding fits with Thornhill and Fincher’s hypothesis.

“Thornhill’s work strikes me as interesting and promising,” says Ronald Inglehart, a political scientist at the University of Michigan in Ann Arbor who was unaware of it before we contacted him. He notes that it is consistent with his own finding that a society needs to have a degree of economic security before democracy can develop. Perhaps this goes hand in hand with a reduction in disease prevalence to signal the move away from collectivism, he suggests.

Inglehart’s comments nevertheless highlights a weakness in the evidence so far assembled in support of the parasite-stress model. An association between disease prevalence and democracy does not necessarily mean that one drives the other. Some other factor may drive both the prevalence of disease in an area and its political system. In their 2009 paper, Thornhill and Fincher managed to eliminate some of the possible “confounders”. For example, they showed that neither a country’s overall wealth nor the way it is distributed can adequately explain the link between the prevalence of disease there and how democratic it is.

But many other possibilities remain. For example, pathogens tend to be more prevalent in the tropics, so perhaps warmer climates encourage collectivism. Also, many of the nations that score high for disease and low for democracy are in sub-Saharan Africa, and have a history of having been colonised, and of frequent conflict and foreign exploitation since independence. Might the near-constant threat of war better explain that region’s autocratic governments? There’s also the possibility that education and literacy would have an impact, since better educated people may be more likely to question authority and demand their rights to a democracy. Epidemiologist Valerie Curtis of the London School of Hygiene and Tropical Medicine thinks such factors might be the ones that count, and says the evidence so far does not make the parasite-stress theory any more persuasive than these explanations.

Furthermore, some nations buck the trend altogether. Take the US and Syria, for example: they have sharply contrasting political systems but an almost identical prevalence of disease. Though even the harshest critic of the theory would not expect a perfect correlation, such anomalies require some good explanations.

Also lacking so far in their analysis is a coherent account of how historical changes in the state of public health are linked to political change. If Thornhill’s theory is correct, improvements in a nation’s health should lead to noticeable changes in social outlook. Evidence consistent with this idea comes from the social revolution of the 1960s in much of western Europe and North America, which involved a shift from collectivist towards individualist thinking. This was preceded by improvements in public health in the years following the second world war – notably the introduction of penicillin, mass vaccination and better malaria control.

There are counter-examples, too. It is not clear whether the opening up of European society during the 18th century was preceded by any major improvements in people’s health, for example. Nor is there yet any clear evidence linking the current pro-democracy movements in the Middle East and north Africa to changes in disease prevalence. The theory also predicts that episodes such as the recent worldwide swine-flu epidemic should cause a shift away from democracy and towards authoritarian, collectivist attitudes. Yet as Holly Arrow, a psychologist at the University of Oregon in Eugene, points out, no effect has been recorded.

Mysterious mechanisms

To make the theory stick, Thornhill and his collaborators will also need to provide a mechanism for their proposed link between pathogens and politics. If cultural changes are responsible, young people might learn to avoid disease – and outsiders – from the behaviour of those around them. Alternatively, the reaction could be genetically hard-wired. So far, it has not proved possible to eliminate any of the possible mechanisms. “It’s an enormous set of unanswered questions. I expect it will take many years to explore,” Schaller says.

One possible genetic explanation involves 5-HTTLPR, a gene that regulates levels of the neurotransmitter serotonin. People carrying the short form of the gene are more likely to be anxious and to be fearful of health risks, relative to those with the long version. These behaviours could be a life-saver if they help people avoid situations that would put them at risk of infection, so it might be expected that the short version of the gene is favoured in parts of the world where disease risk is high. People with the longer version of 5-HTTLPR, on the other hand, tend to have higher levels of serotonin and are therefore more extrovert and more prone to risk-taking. This could bring advantages such as an increased capacity to innovate, so the long form of the gene should be more
common in regions relatively free from illness.

That pattern is exactly what neuroscientists Joan Chiao and Katherine Blizinsky at Northwestern University in Evanston, Illinois, have reported in a paper published last year. Significantly, nations where the short version of the gene is more common also tend to have more collectivist attitudes (Proceedings of the Royal Society B, vol 277, p 529).

It is only tentative evidence, and some doubt that Chiao and Blizinsky’s findings are robust enough to support their conclusions (Proceedings of the Royal Society B, vol 278, p 329). But if the result pans out with further research, it suggests the behaviours involved in the parasite-stress model may be deeply ingrained in our genetic make-up, providing a hurdle to more rapid political change in certain areas. While no one is saying that groups with a higher proportion of short versions of the gene will never develop a democracy, the possibility that some societies are more genetically predisposed to it than others is nevertheless an uncomfortable idea to contemplate.

Should the biases turn out to be more temporary – if flexible psychological reactions to threat, or cultural learning, are the more important mechanisms – the debate might turn to potential implications of the theory. Projects aiming to improve medical care in poor countries might also lead a move to more democratic and open governments, for example, giving western governments another incentive to fund these schemes. “The way to develop a region is to emancipate it from parasites,” says Thornhill.

Remarks like that seem certain to attract flak. Curtis, for instance, bristled a little when New Scientist put the idea to her, pointing out that the immediate threat to human life is a pressing enough reason to be concerned about infectious disease.

Thornhill still has a huge amount of work ahead of him if he is to provide a convincing case that will assuage all of these doubts. In the meantime, his experience following publication of A Natural History of Rape has left him prepared for a hostile reception. “I had threats by email and phone,” he recalls. “You’re sometimes going to hurt people’s feelings. I consider it all in a day’s work.”

Jim Giles is a New Scientist correspondent based in San Francisco