ScienceWeek

SCIENCEWEEK

Briefs in the Sciences

May 30, 2003

Vol. 7 - Number 22B

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CONTENTS:

1. Genetics and the Making of Homo Sapiens

2. Black Smokers and the Origin of Life

3. Nitric Oxide and Hemoglobin

4. Blood Mercury Levels in Women and Children

5. On Nicolaus Copernicus (1473-1543)

6. First Generation vs. Second Generation Stars

7. On the Core of the Planet Mars.

8. On Rosalind Franklin (1920-1958)

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1. GENETICS AND THE MAKING OF HOMO SAPIENS

Nature 2003 422:849

The following points are made by Sean B. Carroll:

1) What makes modern humans different from the great apes and earlier hominids? In what hominids and when in evolution did important physical traits and behaviors appear? Where in our larger brains do human-specific capabilities reside? These have been long-standing questions in palaeoanthropology and comparative anatomy, since the discovery of Neanderthal skulls and the first studies of great apes in the nineteenth century. Now, the mystery of human origins is expanding beyond the description and history of human traits, towards the genetic mechanisms underlying their formation and evolution. With the characterization of the human genome, and that of our chimpanzee cousin on the way, the quest to discover the genetic basis of the physical and behavioral traits that distinguish us from other apes is rapidly gaining momentum.

2) Genomes diverge as a function of time, and most of the sequence changes that accumulate between any two related species are selectively neutral or nearly neutral in that they do not contribute to functional or phenotypic differences. The great challenge is to elucidate the number, identity and functions of genes, and the specific changes within them, that have shaped the evolution of traits. This has been accomplished for only a few traits in model systems, so it is a difficult task for human features about which we know little, and an enormous prospect to consider the whole arc of human evolution.

3) To approach the origins of human traits at the genetic level, it is essential to have as a framework a history of our lineage and the characters that distinguish it. It is inadequate and misleading to consider just the comparative anatomy and development (or genomes) of extant humans, chimpanzees and other apes, and then to attempt to infer how existing differences might be encoded and realized. Each of these species has an independent lineage that reaches back as far or further than hominins ("hominins" refers to humans and our evolutionary ancestors back to the separation of the human and ape lineages; "hominids" to humans and the African apes). The evolution of "modern" traits was not a linear, additive process, and ideas about the tempo, pattern and magnitude of change can only be tested through fossil evidence, which is always subject to revision by new finds. The fossil record continues to shape views of three crucial issues in hominid evolution. First, what distinguishes hominins from the apes? Second, what distinguishes modern humans (Homo sapiens) from earlier hominins? And third, what was the nature of the last common ancestor of hominins and the Pan lineage?

4) In summary: Understanding the genetic basis of the physical and behavioral traits that distinguish humans from other primates presents one of the great new challenges in biology. Of the millions of base-pair differences between humans and chimpanzees, which particular changes contributed to the evolution of human features after the separation of the Pan and Homo lineages 5 7 million years ago? How can we identify the "smoking guns" of human genetic evolution from neutral ticks of the molecular evolutionary clock? The magnitude and rate of morphological evolution in hominids suggests that many independent and incremental developmental changes have occurred that, on the basis of recent findings in model animals, are expected to be polygenic and regulatory in nature. Comparative genomics, population genetics, gene-expression analyses and medical genetics have begun to make complementary inroads into the complex genetic architecture of human evolution.

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2. BLACK SMOKERS AND THE ORIGIN OF LIFE

Andrew Parker: In the Blink of an Eye: [On the Cambrian Explosion]. Perseus Publishing 2003, p.11.

The following points are made by Andrew Parker:

1) Thousands of meters below the ocean surface today, black smoke pours into the water from the submarine ridge known as the Axial Seamount, 300 miles west of the coast of Oregon. As dramatic flashes of color and air flare from the primeval cauldrons or chimneys known as hydrothermal vents, or "black smokers", one can really begin to form images of a very primitive Earth. There is justification in this imagery because black smokers would have emerged with the appearance of the first seas. They mark the separation of boundaries between Earth's massive plates, on which we live, that float on the planet's surface. Up through the gaps created, hot magma oozes out of the Earth's crust to form new sea floor.

2) The unstable concoction of chemicals ejected from the first black smokers reacted with seawater and provided conditions that could have given rise to the inorganic construction of amino acids and other prebiotic organic molecules that are the building blocks for life. Such chemical reactions compare with those found in primitive living creatures today. As one can imagine, chemicals leaving a black smoker are hot. But very primitive bacteria can tolerate temperatures of up to 110› Celsius in today's black smokers, so heat was never a problem for early life. In fact the living representatives of all of life's most primitive species require very hot temperatures to sustain their chemical workings.

3) It is also interesting that black smokers are probably the only places on Earth where the energy of life is not drawn from the sun by means of photosynthesis in an oxygenated atmosphere. The small iron sulfide globules found in the chimneys of the black smokers quite possibly provided the reducing environment necessary to sustain the first life forms. All things considered, black smokers are good candidates for the cradle of life on Earth...

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3. NITRIC OXIDE AND HEMOGLOBIN

New Engl. J. Med. 2003 348:1483

The following points are made by A. Schechter and M. Gladwin:

1) Nitric oxide is a highly reactive molecule with many biologic effects. Its function as the "endothelium-derived relaxing factor" that regulates vascular tone is a central feature of its role as a signaling molecule. Endothelial cells use arginine to produce nitric oxide gas, which diffuses into the surrounding smooth muscle, where it induces relaxation of vascular smooth muscle and dilatation of blood vessels.

2) Nitric oxide produced by endothelial cells also diffuses into the flowing blood, where it reacts with molecules in the plasma and especially oxyhemoglobin in erythrocytes. Nitric oxide is rapidly destroyed by its reaction with the iron-containing heme groups of oxyhemoglobin. This reaction, which produces methemoglobin and nitrate ions, accounts for some of the deleterious effects of blood substitutes based on free hemoglobin, which very efficiently scavenge nitric oxide. Despite the immense amount of hemoglobin in the mass of circulating red cells, which should capture free nitric oxide almost immediately, enough bioactivity of nitric oxide remains to exert control over vascular tone. Indeed, inhibition of nitric oxide synthesis in humans causes marked vasoconstriction. The rapid destruction of nitric oxide by hemoglobin raises the question of whether it is a paracrine agent with only local effects or whether, like a hormone, it disseminates throughout the body. If the gas can act in the manner of a hormone, then it might have considerable pharmacologic usefulness.

3) The confinement of hemoglobin within erythrocytes reduces the rate of the reaction of hemoglobin with nitric oxide by a factor of 1000 or greater because the red-cell membrane creates a barrier to the diffusion of nitric oxide. Furthermore, in rapidly flowing arterial blood, the streaming of plasma along the endothelium separates nitric oxide from much of the red-cell mass, thereby reducing its contact with oxyhemoglobin. Moreover, not all of the reactions of nitric oxide with hemoglobin destroy it. Nitric oxide also reacts with the heme groups of deoxyhemoglobin to form iron-nitrosyl hemoglobin and with the cysteine at position 93 of the beta chain of hemoglobin to form S-nitrosohemoglobin. Although these reactions are rather limited, if either were reversible, then hemoglobin in red cells might act as both a destroyer of nitric oxide and a carrier of the gas in the circulation.

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4. BLOOD MERCURY LEVELS IN WOMEN AND CHILDREN

J. Am. Med. Assoc. 2003 289:1667

The following points are made by S.E. Schober et al:

1) Mercury is widespread in the environment, originating from both natural and anthropogenic sources. The general population may be exposed to 3 forms of mercury: elemental, inorganic, or organic (predominantly methyl). Elemental and inorganic mercury exposure can result from mercury spills, dental amalgams, exposure at the workplace, environmental exposure to natural weathering of mercury containing ores, and from the burning of coal and incineration of medical wastes. Methylmercury is formed through microbial action from inorganic mercury that has deposited in aquatic environments and bioaccumulates through the food chain so that concentrations are highest in large predatory fish. Exposure occurs primarily through consumption of seafood, freshwater fish, and shellfish.

2) Methylmercury exposure is of particular concern because it is a well-established human neurotoxin and the developing fetus is most sensitive to its adverse effects. Toxic effects of methylmercury exposure are known from past poisoning outbreaks, particularly those in Minamata, Niigata, and Kumomoto Prefecture, Japan, and in Iraq. Recent epidemiological studies have addressed neurodevelopmental effects in young children from in utero methylmercury exposure in populations in which fish or seafood is a substantial component of the diet and in which exposure levels may be comparable with those levels in high-end consumers in the United States.

3) The authors present data from the 1999-2000 National Health and Nutrition Examination Survey (NHANES) on the distribution of blood mercury levels and the association with sociodemographic covariates and fish and shellfish consumption in a representative sample of young children and women of reproductive age. The authors conclude: Measures of mercury exposure in women of childbearing age and young children generally fall below levels of concern. However, approximately 8% of women had concentrations higher than the US Environmental Protection Agency's recommended reference dose (5.8 micrograms/L), below which exposures are considered to be without adverse effects. Women who are pregnant or who intend to become pregnant should follow federal and state advisories on consumption of fish.

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5. ON NICOLAUS COPERNICUS (1473-1543)

American Scientist 2003 91:111

The following points are made by Philip Morrison:

1) Nicolaus Copernicus is the Latinate name of the renowned astronomer and polymath, born in 1473 to a well-placed mercantile family in the Polish town of Torun. (Note that in those parts, national frontiers, place names and even shorelines shift over the centuries.) The bright boy, who at age 10 lost his father, found a generous guardian in his uncle Lucas, who soon became a bishop, his see including the Frombork cathedral, set on the shore of the delta of the river Vistula in northern Poland. Mathematics and astronomy drew the young student in time to the national university at Krakow. He continued study at three celebrated Italian universities and returned to Baltic shores at around age 30, as Doctor of Canon Law, Licentiate in Medicine and astronomical revolutionary.

2) For years thereafter he attended his bishop uncle as official physician; in fact, most of his life was passed fulfilling a dozen diverse appointments as a church official going wherever in stormy times a learned and productive mind was of use. He made maps, attended legislative bodies, held a variety of fiscal posts, acted as diplomat and as civil and military inspector, even wrote a treatise on the minting of money by the new Prussian states. With age he rose to higher administrative positions, although he probably never became a priest.

3) By his thirties Copernicus had developed a heliocentric theory of the Solar System in a document of a few fruitful pages. He improved and circulated it privately in Italy, and during quieter years with his bishop. That phase passed when Lucas died in 1512, and Copernicus embarked on long and varied service for and around the Frombork cathedral.

4) His celebrated full volume, _On the Revolutions of the Celestial Spheres_, was published three decades later, in Nuremberg in 1543, the year he died. He may never have seen it in print. His almanac tables, showing the moon and Earth with the planets revolving about the sun, met the test of expert observation as well as the old Earth-centered tables had. His literary executors were seriously worried about the impact of his new work; one of them added a preface to temper the author's well-supported claims.

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Related Material:

ON NICOLAUS COPERNICUS

What is called the "Copernican Revolution" is considered to be one of the most momentous events in the history of modern natural science, an event that exemplifies the rise of the "world-view" of modern civilization. But the "event" was more an era than a single historical occurrence. The Copernican Revolution was prolonged and complex, beginning shortly before 1514, when Copernicus first described his theory that the Earth is a planet in motion around the Sun, and extending to the year 1687, when Isaac Newton published Principia Mathematica, which incorporated Copernican principles in the construction of a dynamical astronomy.

Copernicus developed his theory during a period of approximately 30 years, working out the system in full mathematical detail in order to demonstrate how planetary positions could be calculated with this new basis. Copernicus was apparently able with his theory to determine the length of the Earth year to within 28 seconds. Although the work of Nicolas Copernicus (1473-1543) (born Mikolaj Kopernik) may have marked the beginning of the important conceptual revolution that bears his name, very little is actually known about Copernicus personally, and his burial place in the town of Frombork in Poland is now unlocated.

Rosemary Sullivant (Astronomy 1999 October) presents a biographical essay on Copernicus, the author making the following points:

1) Copernicus lived a circumscribed life as a physician and civil servant within the Catholic Church. Little is known about him, and most of his papers have been lost. He studied painting before medicine, but only copies of his self-portraits remain.

2) Copernicus was born 19 February 1473 in the Polish city of Torun, then part of Prussia. He was born into a prosperous and politically connected family, and his early professional life was directed by his uncle, Lucas Watzenrode, a powerful Church official. Copernicus eventually received an appointment as a canon of the cathedral in Frombork, where he passed most of his life. He never married.

3) It is believed that Copernicus began writing his magnum opus, _De Revolutionibus_, around 1515. He had already outlined his theory that the Earth revolves around the Sun before 1514. As Copernicus continued work on _De Revolutionibus_ throughout the 1530s, interest in his work grew. In 1533, Pope Clement VII was told about the theory of Copernicus, and several high Church officials wrote to Copernicus to say they admired his work and to offer to pay all his expenses. Copernicus was also urged to publish his work without delay.

4) But in addition to approval of his work, significant criticism existed. In 1539, Martin Luther wrote: "Mention has been made of some new astrologer, who wanted to prove that Earth moves and goes around, and not the firmament or heavens, the sun and moon... This fool wants to turn the entire art of astronomy upside down! But as the Holy Scriptures show, Joshua ordered the sun, and not Earth, to halt!" Protestants were initially more hostile to Copernicus; the Catholic resistance developed later.

5) In June of 1542, Copernicus dedicated the preface of _De Revolutionibus_ to Pope Paul III: "I can easily conceive, most Holy Father, that as soon as some people learn that in this book which I have written concerning the revolutions of the heavenly bodies, I ascribe certain motions to Earth, they will cry out at once that I and my theory should be rejected." Copernicus added that his work had been motivated by "the uncertainty of the traditional mathematical methods of calculating the motions of the celestial bodies," and he appealed to the Pope to "suppress the bites of slanderers." Copernicus died 14 May 1543, the day the finished book was placed in his hands [*Note #1]

Notes:

*Note #1: The book _De Revolutionibus_ was a collection of very different materials. Its bulk was mathematical astronomy, in which Copernicus first recast the reference frames for observation and then produced his revised models for the moving bodies. Before the mathematical section there appeared Book I, an argument for the reality of the Earth's motions based on various heuristic considerations. At the beginning of the book was a preface by Copernicus, describing the problems he had solved and warning that astronomy is a matter for experts. Before the preface was an unsigned note addressed to the reader, the note consisting of an apology for the strange theory and a disclaimer that it represented reality. This note was apparently not written by Copernicus, but by Andreas Osiander (1498-1552), who saw the book through the press, and who apparently wrote the note to avoid possible trouble from theologians. It is perhaps of some significance that as an initiator of a cultural conceptual revolution, Copernicus has a parallel in Darwin, who initiated what is called the "Darwinian Revolution" in our cultural conception of the human species as a biological entity, a cultural conceptual revolution not yet complete and still under attack by non-experts.

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6. FIRST GENERATION VS. SECOND GENERATION STARS

Nature 2003 422:871

The following points are made by H Umeda and K. Nomoto:

1) It has been proposed theoretically that the first generation of stars in the Universe ("population III stars") would be as massive as 100 solar masses (100 M), because of inefficient cooling of the precursor gas clouds. Recently, the most iron-deficient (but still carbon-rich) low-mass star -- HE0107 5240 --was discovered. If this is a population III star that gained its metals (elements heavier than helium) after its formation, it would challenge the theoretical picture of the formation of the first stars.

2) The authors report that the patterns of elemental abundance in HE0107 5240 (and other extremely metal-poor stars) are in good accord with the nucleosynthesis that occurs in stars with masses of 20 130 M when they become supernovae if, during the explosions, the ejecta undergo substantial mixing and fallback to form massive black holes. Such supernovae have been observed. The abundance patterns are not, however, consistent with enrichment by supernovae from stars in the range 130 300 M.

3) The authors accordingly propose that the first-generation supernovae came mostly from explosions of 20 130 M stars; some of these produced iron-poor but carbon- and oxygen-rich ejecta. Low-mass second-generation stars, like HE0107 5240, could form because the carbon and oxygen provided pathways for the gas to cool.

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7. ON THE CORE OF THE PLANET MARS.

Science 2003 300:260

The following points are made by Veronique Dehant:

1) Mars is a planet very similar to Earth. Early in their evolution, both planets must have been sufficiently hot to be molten. Earth still has a liquid core, but the smaller size of Mars would favor faster cooling. Extrapolation from Earth suggests that Mars today should therefore not have a liquid core. However, small differences in elemental composition between the two planets prevent our simply extrapolating from knowledge of Earth's properties. Yoder et al. (Science 2003 300:299) have presented evidence that the iron core of Mars is liquid, with important implications for martian geology.

2) There are several constraints on Mars' deep interior based on analysis of martian meteorites, observation of the absence of a global magnetic field, and knowledge of the planet's mass and moments of inertia. Moments of inertia quantify the global mass repartition within Mars. They provide evidence for the existence of a denser martian core and can be used to constrain the core dimension. However, the uncertainty of the core's density and dimension remains large because they depend on the temperature profile and light element abundance, and these properties are still unknown.

3) Researchers interested in modeling the martian interior are therefore looking for other kinds of complementary data. As for Earth, the Sun's gravitational attraction induces global phenomena on Mars -- namely, tides and precession-nutation (the motion of the rotation axis in space). Tides are deformations induced by the gravitational pull of the Sun. They are related to surface displacements, surface gravity changes (such as those that would be measured by a gravimeter on the martian surface), and mass repartitioning inside the planet. These changes are periodic, with periods related to Mars's orbit around the Sun (and, to a minor extent, to the orbits of the two martian moons, Phobos and Deimos, around Mars).

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8. ON ROSALIND FRANKLIN (1920-1958)

Physics Today 2003 March

The following points are made by Lynne Osman Elkin:

1) In 1962, James Watson, then at Harvard University, and Cambridge University's Francis Crick stood next to Maurice Wilkins from King's College, London, to receive the Nobel Prize in Physiology or Medicine for their "discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material." Watson and Crick could not have proposed their celebrated structure for DNA as early in 1953 as they did without access to experimental results obtained by Ring's College scientist Rosalind Franklin. Franklin had died of cancer in 1958 at age 37, and so was ineligible to share the honor. Her conspicuous absence from the awards ceremony -- the dramatic culmination of the struggle to determine the structure of DNA -- probably contributed to the neglect, for several decades, of Franklin's role in the DNA story. She most likely never knew how significantly her data influenced Watson and Crick's proposal.

2) Franklin expressed an early fascination with physics and chemistry classes at the academically rigorous St. Paul's Girls' School in London, and she earned a bachelor's degree in natural sciences with a specialty in physical chemistry. The degree was earned at Newnham College, Cambridge in 1941.

3) From 1942 to 1946, Franklin did war-related graduate work with the British Coal Utilization Research Association. That work earned her a PhD from Cambridge in 1945, and an offer to join the Laboratoire Central des Services Chimiques de 1'Etat in Paris. She worked there, from 1947 to 1950, with Jacques Mering and became proficient at applying x-ray diffraction techniques to imperfectly crystalline matter such as coal. In the period 1946-49, she published five landmark coal-related papers, still cited today, on graphitizing and nongraphitizing carbons. By 1957, she had published an additional dozen articles on carbons other than coals. Her papers changed the way physical chemists view the microstructure of coals and related substances.

4) Franklin made many friends in the Paris laboratory and often hiked with them on weekends. She preferred to live on her own modest salary and frustrated her parents by continually refusing to accept money from them. She excelled at speaking French and at French cooking and soon became more comfortable with intellectual and egalitarian "French ways" than with conventional English middle-class customs. Consequently, she did not fit in well at King's College, where she worked on DNA from 1951 to 1953. Franklin chose to leave King's and, in the spring of 1953, moved to Birkbeck College. After the move to Birkbeck, she began her celebrated work with J. Desmond Bernal (1901-1971) on RNA viruses like tobacco mosaic virus (TMV). She was a cautious scientist who began to trust her intuition more as she matured. She published 14 papers about viruses between 1955 and 1958, and completed the research for three others that colleague Aaron Klug submitted for publication after her death.

5) In his obituary for Franklin, Bernal described her as a "recognized authority in industrial physico-chemistry." In conclusion, he wrote, "As a scientist, Miss Franklin was distinguished by extreme clarity and perfection in everything she undertook. Her photographs are among the most beautiful of any substances ever taken."

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