Monday, November 26, 2007

Skin Cells and Ethics

This from the Times of India

"Using deactivated viruses, the scientists managed to transport four key genes into the nucleus of the skin cells which reprogrammed them into cells virtually identical to embryonic stem cells.......Of far greater import, though, is the fact that till today the only way stem cells could be obtained was from embryos which had to be destroyed while they were harvested. The new discovery neatly sidesteps this hassle area and deftly diffuses the huge political firestorm generated over the morality of stem cell research. The method avoids the use of human reproductive materials altogether - no egg, no embryo and no cloning technique at all".

The editorial describes a technique which used a retrovirus to insert four genes into the genome of an adult skin cell which induces the skin cell to be reprogrammed to behave like embryonic stem cells. As far as the researchers could tell the reprogrammed skin cell behaves just like an embryonic stem cell potentially capable of diversifying into different specialized cell types. It then comes to the conclusion that this discovery means a freedom from using embryonic stem cells for research.

TOI has come to a somewhat hasty conclusion. The four genes that the researchers used to reprogram the skin cell genome were first identified through research on embryonic stem cells. The implication is that research on any novel methods to induce adult cells into becoming pluripotent and on developing into specialized cells without developmental defects or the risk of inducing diseases like cancer will rely on a deeper understanding of how embryonic stem cells work naturally. We don't understand this process completely yet and so there is no getting away from embryonic stem cell research at least for the near future.

TOI then claims

"But at least as far as ethical bans and restrictive government funding are concerned, they've been blown away".

Which government's views is TOI talking about? India already funds embryonic stem cell research and therapeutic cloning. Unlike the United States, destruction of embryos for research purposes has not posed any major ethical dilemmas and therapeutic cloning is widely supported by civil society. TOI's concerns don't reflect those of Indian society at large.

Tuesday, November 20, 2007

LiveScience Ignores Basic Genetics


"Researchers find that males can respond quicker than females to sexual selection, resulting in glitzier garbs like the male peacock's tail feather, which outshows any drab peahen". This appeared as an accompaniment to an article discussing research which showed how males with a "simpler" genetic arrangement of XY sex-determining chromosomes may evolve faster than females with a XX arrangement.

I posted on this a couple of days ago commenting:

"Sexual selection though may not be the best example to illustrate the connection between "simple genetic variability" and faster evolution. The reason is the peacock' s tail. This particular study uses the fly Drosophila melanogaster which has an XY (male) / XX (female) sex determination system. But in birds, the system is different. It is the males which are ZZ and females ZW. So, females have a "simple genetic system" yet it is the peacock that evolves the elaborate tail."

The genetic explanation put forth by these researchers to explain why sexual selection commonly occurs via males clearly cannot be extended to birds. Yet LiveScience one of the biggest science portals ignoring basic genetics have a photo of a peacock and a caption clearly meant as an example supporting the researchers hypothesis.

How can science reporting from such a portal become so awry and careless? The original paper clearly made no mention of peacocks or birds, but relied on fruit fly genetics to tease out the results. The mindless extrapolation to birds is a creation of the media. Is this the fault of the science writer, in this case Jeanna Bryner, or was there some editorial oversight insisting that a photo of a splendid peacock's tail will go along nicely with the sexual selection theme?

Its website claims that "It has become a trusted news source and its content is syndicated regularly on major news portals such as Yahoo!, MSNBC, Fox News and AOL." With such major goof ups I am not so sure I can trust them for my daily dose of science news. Readers of Yahoo!, MSNBC, Fox News and AOL also be warned!

Sunday, November 18, 2007

Simple Males Evolve Faster

A press release titled Males being "simple" evolve faster appeared in the Times of India. It covered a research paper Simpler mode of inheritance of transcriptional variation in male Drosophila melanogaster: published in PNAS. The researchers pointed out that since males are hemizygous i.e . have X and Y sex chromosomes they have more additive genetic variation (variation in traits are due to variation in genes without dominance effects or gene interaction effects), while females with XX sex chromosomes exhibit non-additive genetic variation. Since males have only one X chromosome, they may -unlike females - lack the complementary allele on the corresponding sex (Y) chromosome. In females any beneficial mutation may not necessarily be expressed as the effect of that gene may be masked by the complementary allele, meaning the trait is expressed through dominance. This would mean that it will be hard for that particular version of the gene to increase in frequency since you would need two copies of that gene (recessive) for it to be expressed and subjected to natural selection. In contrast, since males have just one copy of many sex-linked genes, any beneficial mutation will be expressed and face selection, leading to a rapid frequency increase of the gene over few generations. Therefore this type of sex-linked genetic variation in males responds more quickly to selection than the one found in females. More response to selection pressure, faster evolution. Biologist David Rand, of Brown University explains it well "This research shows how recessive and dominant traits are important in determining variation in populations. The best way to think of it is males play with one card, but females get to play one and hold one. If males have got a good trait, it's promoted; something bad, it's eliminated. In females you can have a bad card, but a good card can protect it. As a result, females can carry deleterious traits but not express them."

Interesting stuff. The researchers then add that sexual selection usually operates via males due to this difference in the type of genetic variability. Sexual selection leads to dimorphism, i.e. males and females develop divergent morphologies. In many species it is the males that become bigger or develop large antlers or bright ornamentation. The usual explanation for this: Males have more variable reproductive success than females and tend to be more promiscuous. Females due to a large investment in the gamete are more choosy. So males compete for female attention leading to bigger, stronger, showier males over time. The researchers of this study argue that the simpler genetic inheritance system coupled with the more variable reproductive success of males would help males evolve via sexual selection pressures more rapidly.

Sexual selection though may not be the best example to illustrate the connection between "simple genetic variability" and faster evolution. The reason is the peacock' s tail. This particular study uses the fly Drosophila melanogaster which has an XY (male) / XX (female) sex determination system. But in birds, the system is different. It is the males which are ZZ and females ZW. So, females have a "simple genetic system" yet it is the peacock that evolves the elaborate tail. Even in species where sexual selection operates via XY males, does that really mean males are evolving faster than females as the titles of virtually all press releases implied? Sexual selection in males is fueled by female choice, which is a genetically determined trait. Which means that female discrimination for a mate and male ornamentation will evolve in tandem at the same pace.

Wednesday, November 14, 2007

Deccan Volcanism and Mass Extinctions

Science and the scientific method is about eternal vigilance, the need to question even well "proven" theory, to prevent theory from turning into dogma, to make sure that "mainstream thinking" does not fossilize into inertia and a reluctance to question "established facts". This post is about how one such well established theory may turn out to be wrong.

During the Paleozoic period the earth has seen five mass extinctions, great dyings, where a significant proportions of the earth's biota has gone extinct within a short period of time. These five extinctions took place in the Ordovician-Silurian, Late Devonian, Permian-Triassic, Triassic-Jurassic, and Cretaceous-Tertiary. Of these, the Permian-Triassic was the mother of all extinctions in which about 95% of species perished. The most famous however is the Cretaceous-Tertiary event in which about 50% of all species including the non-avian dinosaurs went extinct. The reason for a high public profile has been the dramatic explanation for this extinction and also some very famous victims. In the early 1980's physicist Luis Alvarez, his son geologist Walter Alvarez, and chemists Frank Asaro and Helen Michels discovered a high concentration of iridium in rocks at the Cretaceous-Tertiary boundary (K-T). Since iridium is rare in the earth's crust but is common in asteroids, the scientists suggested that the earth was hit by a large asteroid around 65 million years ago, causing environmental stresses and the late Cretaceous extinction. In 1991 in the Yucatan peninsula in Mexico, a large impact crater named the Chicxulub Crater was discovered. This was dated to around 65 million years. The cause was assumed to be found and it became accepted wisdom that the Cretaceous dying was caused by the Chicxulub impact event. The theory quickly took hold over public imagination. The dinosaur story was retold through countless documentaries, popular articles and books, one of the most famous being T rex and the crater of doom by Walter Alvarez. There was just something satisfying about these fearsome creatures who dominated terrestrial ecosystems for over 150 million years being wiped out suddenly by a weapon of mass destruction from outer space.

But nature is never that simple. The facts as always are messy and the Cretaceous extinction story has gotten messier. Mounting evidence reported in various media outlets in the past few months to week here, here and here suggest that the late Cretaceous extinction was not caused by the Chicxulub impact event but had multiple causes including the gigantic Deccan volcanic eruption at the end of the Cretaceous. I live in the Deccan volcanic province and so this a exciting news to me. All those basalt layers that I see everyday may have played a role in changing earth history. The champion of this hypothesis in palaeontologist Gerta Keller who over the last few years has assembled some impressive evidence in support of her theory. First is the debunking of the conventional wisdom that the Chicxulub impact event caused the mass extinction. Keller and her research team drilled and recovered cores from the impact site in Mexico and from another site along Brazos river in Texas, some 1700 km from the impact site. Their detailed analysis of the sedimentological, geochemical and palaeontological aspects of the cores revealed that a) the impact took place almost 300,000 years before the K-T mass extinction b) the impact is recorded by characteristic sedimentary rocks known as breccia (rock containing pulverized and fragmented pieces) and as layers rich in glass spherules which form by the heat and shock of the impact. An analysis of the biota in the sediment below and above this impact layer shows no evidence of accelerated extinction or stressed ecosystems. It appears that the Chicxulub event had little impact on the earth's biota let alone trigger a mass extinction.

Second, Keller has now managed to come up with evidence tying the Deccan volcanics to this mass extinction and this evidence comes from Rajamundhry, Andhra Pradesh, India. A small digression at this point. Travelling to Rajamundhry is a fantastic experience because of the wide bridge across the Godavari River as you approach Rajamundhry from Hyderabad. I crossed it by train at sunset, and the Godavari is an awesome sight. Image below shows the railway bridge.

Back to volcanics. There always have been suggestions that the Deccan volcanics played a role in the late Cretaceous mass extinctions, but due to large uncertainties in establishing the time span of the main eruptive phase it was difficult to establish a link between the volcanism, environmental stresses and extinction. Recent dating of the Deccan basalts indicate that 80% of the volcanism took place in what is known as C29R magnetic polarity zone, which spans the K-T boundary and the mass extinction event (R means that the earth's magnetic field had reversed polarity at that time).

Figure to the left shows the magnetic stratigraphy of the Deccan basalts. Several thousand feet of basalt were erupted in C29R confirming that the volume of basalt erupting at the very end of the Cretaceous over a short period of time must have been enormous, resulting in the release of carbon dioxide and sulphur dioxide in amounts large enough to alter the earth's climate. In Rajamundhry Keller and her team found layers of sediment sandwiched between two Deccan basalt flows. The lower flow was found to have erupted in C29R magnetic polarity, probably coinciding with the K-T event. The sediment above this flow provides a more direct evidence for this connection between the timing of basalt eruption and extinction. They contain early Tertiary post-extinction foraminifera. This biota marks the initial evolution of the foraminifera after the K-T event indicating that the mass extinction must have taken place during the eruption of the main phase of the Deccan volcanics. In detail, the sediments contained foraminifera fossils of early Danian age, which showed that these sediments were deposited in the earliest Tertiary period, and thus were a window into conditions just after the mass extinction and offered to provide a link between volcanism and environmental stresses. Unlike the sequence of fossils spanning the Chicxulub impact layer in Mexico and Texas, the fossils here at Rajamundhry show evidence of stressed ecosystems. The early post-extinction Danian foramainfera are less diverse, tiny, without any ornamentation and show deformities unlike pre-extinction late Cretaceous (Maastrician) foraminifera which are diverse, larger and ornate. This compares well with foraminifera of Danian age elsewhere, suggesting that the conditions recorded in the intertrappean sediments at Rajamundhry are representative of global post-extinction stress. The biota in these sediments suggest that post-extinction recovery of ecosystems was slow. Volcanism continued into the early Tertiary as indicated by the lava flow overlying these sediments. This flow falls in C29N (N means normal polarity) magnetic polarity and occurred about 280,000 years after the K-T event. This continued volcanism Keller suggests may be the reason why ecosystems took so long to recover from the mass extinction. Another small digression. In the figure above of the magnetic stratigraphy, a large part of C29R is made up of the Wai and Lonavala subgroups and the bulk of the C29N by the Mahabaleshwar formation. These are names which must be familiar to readers from Maharashtra. The basalts comprising these subgroups make up the precipitous western ghat escarpment. So, the next time you are standing at Arthur's Seat in Mahabaleshwar (image below), contemplate on the possibility that you are looking at the volcanic pile which altered the course of evolution.

So this is where things stand today. Did I cover everything? Readers may notice a nagging discrepancy. If the Chicxulub impact occured 300,000 years before the K-T boundary, then what caused the irridium anomaly at the boundary? It is no doubt of extraterrestrial origin and so there must have been another asteroid impact that coincided with the peak basalt volcanism. The impact crater has not been found, but expect the story to get even more complicated.

And yes, the Indian media screwed up on this one too. The Times of India (Nov. 8 2007) copied and pasted an article by John Noble Wilford from the New York Times. The article was about some fossil discoveries from post-extinction sediments in New Jersey which showed that some species of Cretaceous ammonoids survived the mass extinction for at least several hundred years. But the connection between the Cretaceous extinction and dinosaurs has become so ingrained that The Times of India in a bombastic subtitle ignored the evidence presented in the article and announced that it was the dinosaurs who lived hundreds of years after the extinction event , for which there is no evidence..... yet.

Friday, November 2, 2007

Images of Alzheimer's

An article in Science Daily about Alzheimer's caught my eye. Brain imaging is rapidly evolving into a powerful tool to diagnose various types of brain disorders. In this study, a positron emission tomography (PET) scan of sugar uptake by the brain allows a more accurate diagnosis of a type of dementia frequently mis-diagnosed as Alzheimer's. This will allow for earlier detection and better treatment of dementia. Modern imaging methods like PET and Magnetic Resonance Imaging (MRI) allows us to peek into our brains and observe the effects of the disease. In multicolor these images can show loss of brain tissue as with MRI and patterns of metabolism as with PET. But these images are clinical. They don't portray the emotional turmoil the patient must be going through, the sense of loss and a steady inexorable distancing from the familiar world. How can a machine capture this personal catastrophe? I was reminded of a different kind of image of Alzheimer's in an article I read several years ago.

In 1997 artist William Utermohlen, was diagnosed with Alzheimer's when he was 60 years old. He captured the ravages of the disease in a series of haunting self-portraits. Soon after his last sketch in 2000, the artist stopped painting. He is now in a nursing home.




Galerie Beckel Odille Boicos, Paris

A picture is worth a thousand words. So true!