Showing posts with label DNA. Show all posts
Showing posts with label DNA. Show all posts

Tuesday, August 18, 2009

Shadows of doubt on DNA evidence?


An evil prosecutor could do this. I wonder if it has been done in the past. It is interesting to note that no defense attorney [yet] has challenged the efficacy of the laboratories and techniques let alone the crime scene investigators. Errors can occur.

"DNA Evidence Can Be Fabricated, Scientists Show"

by

Andrew Pollack

August 18th, 2009

The New York Times

Scientists in Israel have demonstrated that it is possible to fabricate DNA evidence, undermining the credibility of what has been considered the gold standard of proof in criminal cases.

The scientists fabricated blood and saliva samples containing DNA from a person other than the donor of the blood and saliva. They also showed that if they had access to a DNA profile in a database, they could construct a sample of DNA to match that profile without obtaining any tissue from that person.

“You can just engineer a crime scene,” said Dan Frumkin, lead author of the paper, which has been published online by the journal Forensic Science International: Genetics. “Any biology undergraduate could perform this.”

Dr. Frumkin is a founder of Nucleix, a company based in Tel Aviv that has developed a test to distinguish real DNA samples from fake ones that it hopes to sell to forensics laboratories.

The planting of fabricated DNA evidence at a crime scene is only one implication of the findings. A potential invasion of personal privacy is another.

Using some of the same techniques, it may be possible to scavenge anyone’s DNA from a discarded drinking cup or cigarette butt and turn it into a saliva sample that could be submitted to a genetic testing company that measures ancestry or the risk of getting various diseases. Celebrities might have to fear “genetic paparazzi,” said Gail H. Javitt of the Genetics and Public Policy Center at Johns Hopkins University.

Tania Simoncelli, science adviser to the American Civil Liberties Union, said the findings were worrisome.

“DNA is a lot easier to plant at a crime scene than fingerprints,” she said. “We’re creating a criminal justice system that is increasingly relying on this technology.”

John M. Butler, leader of the human identity testing project at the National Institute of Standards and Technology, said he was “impressed at how well they were able to fabricate the fake DNA profiles.” However, he added, “I think your average criminal wouldn’t be able to do something like that.”

The scientists fabricated DNA samples two ways. One required a real, if tiny, DNA sample, perhaps from a strand of hair or drinking cup. They amplified the tiny sample into a large quantity of DNA using a standard technique called whole genome amplification.

Of course, a drinking cup or piece of hair might itself be left at a crime scene to frame someone, but blood or saliva may be more believable.

The authors of the paper took blood from a woman and centrifuged it to remove the white cells, which contain DNA. To the remaining red cells they added DNA that had been amplified from a man’s hair.

Since red cells do not contain DNA, all of the genetic material in the blood sample was from the man. The authors sent it to a leading American forensics laboratory, which analyzed it as if it were a normal sample of a man’s blood.

The other technique relied on DNA profiles, stored in law enforcement databases as a series of numbers and letters corresponding to variations at 13 spots in a person’s genome.

From a pooled sample of many people’s DNA, the scientists cloned tiny DNA snippets representing the common variants at each spot, creating a library of such snippets. To prepare a DNA sample matching any profile, they just mixed the proper snippets together. They said that a library of 425 different DNA snippets would be enough to cover every conceivable profile.

Nucleix’s test to tell if a sample has been fabricated relies on the fact that amplified DNA — which would be used in either deception — is not methylated, meaning it lacks certain molecules that are attached to the DNA at specific points, usually to inactivate genes.


FBI telling a FIB?

Ivans...FBI's trail of blunders & tragic end

Saturday, April 18, 2009

DNA database


"If you haven’t done anything wrong, you have nothing to fear," he said.

This is a matter of concern.

"F.B.I. and States Vastly Expand DNA Databases"

by

Solomon Moore

April 19th, 2009

The New York Times

Law enforcement officials are vastly expanding their collection of DNA to include millions more people who have been arrested or detained but not yet convicted. The move, intended to help solve more crimes, is raising concerns about the privacy of petty offenders and people who are presumed innocent.

Until now, the federal government genetically tracked only convicts. But starting this month, the Federal Bureau of Investigation will join 15 states that collect DNA samples from those awaiting trial and will also collect DNA from detained immigrants — the vanguard of a growing class of genetic registrants.

The F.B.I., with a DNA database of 6.7 million profiles, expects to accelerate its rate of growth from 80,000 new entries a year to 1.2 million by 2012 — a 17-fold increase. F.B.I. officials say they expect DNA processing backlogs — which now stand at more than 500,000 cases — to increase.

Law enforcement officials say that expanding the DNA databanks to include legally innocent people will help solve more violent crimes. They point out that DNA has helped convict thousands of criminals and has exonerated more than 200 wrongfully convicted people.

But criminal justice experts cite Fourth Amendment privacy concerns and worry that the nation is becoming a genetic surveillance society.

"DNA databases were built initially to deal with violent sexual crimes and homicides — a very limited number of crimes," said Harry Levine, a professor of sociology at City University of New York who studies policing trends. "Over time more and more crimes of decreasing severity have been added to the database. Cops and prosecutors like it because it gives everybody more information and creates a new suspect pool."

Courts have generally upheld laws authorizing compulsory collection of DNA from convicts and ex-convicts under supervised release, on the grounds that criminal acts diminish privacy rights.

DNA extraction upon arrest potentially erodes that argument, a recent Congressional study found. "Courts have not fully considered legal implications of recent extensions of DNA-collection to people whom the government has arrested but not tried or convicted," the report said.

Minors are required to provide DNA samples in 35 states upon conviction, and in some states upon arrest. Three juvenile suspects in November filed the only current constitutional challenge against taking DNA at the time of arrest. The judge temporarily stopped DNA collection from the three youths, and the case is continuing.

Sixteen states now take DNA from some who have been found guilty of misdemeanors. In South Carolina in 2007, a court ordered a DNA sample to be taken from a man found guilty of loitering for the purpose of prostitution.

As more police agencies take DNA for a greater variety of lesser and suspected crimes, civil rights advocates say the government’s power is becoming too broadly applied. "What we object to — and what the Constitution prohibits — is the indiscriminate taking of DNA for things like writing an insufficient funds check, shoplifting, drug convictions and other cases where police don't have a need to obtain DNA because it’s not relevant to charges facing them," said Michael Risher, a lawyer for the American Civil Liberties Union.

This year, California began taking DNA upon arrest and expects to nearly double the growth rate of its database, to 390,000 profiles a year from 200,000.

One of those was Brian Roberts, 29, who was awaiting trial for methamphetamine possession. Inside the huge Twin Towers Correctional Facility in Los Angeles last month, Mr. Roberts let a sheriff’s deputy swab the inside of his cheek.

Mr. Roberts's DNA will be translated into a numerical sequence at the F.B.I.'s DNA database, the largest in the world.

The system will search for matches between Mr. Roberts's DNA and other profiles every Monday, from now into the indeterminate future — until one day, perhaps decades hence, Mr. Roberts might leave a drop of blood or semen at some crime scene.

Law enforcement officials say that DNA extraction upon arrest is no different than fingerprinting at routine bookings and that states purge profiles after people are cleared of suspicion. In practice, a number of defense lawyers say this is a laborious process that often involves a court order. (The F.B.I. says it has never received a request to purge a profile from its own database.)

When DNA is taken in error, expunging a profile can be just as difficult. In Pennsylvania, where DNA cannot be taken from juveniles for misdemeanors, Ellyn Sapper, a Philadelphia public defender, has spent weeks trying to expunge the profile of a 14-year-old boy guilty of assault and bicycle theft — his first misdemeanor. "I'm going to have to get a judge's order to make sure that all references to his DNA are gone," she said.

The police say that the potential hazards of genetic surveillance are worth it because it solves crimes and because DNA is more accurate than other physical evidence. "I've watched women go from mug-book to mug-book looking for the man who raped her," said Mitch Morrissey, the Denver district attorney and an advocate for more expansive DNA sampling. "It saves women's lives."

Mr. Morrissey pointed to Britain, which has fewer privacy protections than the United States and has been taking DNA upon arrest for years. It has a population of 61 million — and 4.5 million DNA profiles. "What you find is that about 8 percent of the people commit about 70 percent of your crimes, so if you can get the majority of that community, you don’t have to do more than that," he said.

In the United States, 8 percent of the population would be roughly 24 million people.

Britain may provide a window into America's genetic surveillance future: As of March 2008, 857,000 people in the British database, or about one-fifth, have no current criminal record. In December, the European Court of Human Rights ruled that Britain's practice of collecting DNA profiles from innocent people, including children as young as 10, violated international privacy protections.

Critics are also disturbed by the demographics of DNA databases, and again Britain’s example is instructive. According to a House of Commons report, 27 percent of black people and 42 percent of all black males are genetically registered, compared with 6 percent of white people.

As in Britain, expanding genetic sampling in the United States could exacerbate racial disparities in the criminal justice system, according to Hank Greely, a Stanford University Law School professor who studies the intersection of genetics, policing and race. Mr. Greely estimated that African-Americans, who are about 12 percent of the national population, currently make up 40 percent of the DNA profiles in the federal database, reflective of their prison population. He also expects Latinos, who are about 13 percent of the population and committed 40 percent of last year's federal offenses — nearly half of them immigration crimes, including illegal entry — to dominate DNA databases.

Enforcement officials contend that DNA is blind to race. Federal profiles include little more information than the DNA sequence and the referring police agency. Subjects’ names are usually kept by investigators.

Rock Harmon, a former prosecutor for Alameda County, Calif., and an adviser to crime laboratories, said DNA demographics reflected the criminal population. Even if an innocent man's DNA was included in a genetic database, he said, it would come to nothing without a crime scene sample to match it. "If you haven't done anything wrong, you have nothing to fear," he said.

Sunday, January 25, 2009

Galileo's unilateral myopia/creeping angle closure glaucoma


"One of the "errors" that Galileo made...is that he believed Saturn was not perfectly round but may have had an irregular, inflated side."

So postulates Paolo Galluzzi the director of the Museum of History and Science in Florence. He and Peter Watson wish to exhume Galileo's body and extract some DNA and subject it to a science model to determine the status of Galileo's eyesight. I'm not sure a sample can be taken. And even if a sample is acquired wouldn't it have been subject to some contamination.

"Scientists want to test Galileo's remains"

by

Philip Pullella

January 23rd, 2009

Reuters

ROME - Italian and British scientists want to exhume the body of 16th-century astronomer Galileo for DNA tests to determine if his severe vision problems may have affected some of his findings.

The scientists told Reuters yesterday that DNA tests would help answer some unresolved questions about the health of the man known as the father of astronomy, whom the Vatican condemned for teaching that the Earth revolves around the sun.

"If we knew exactly what was wrong with his eyes we could use computer models to re-create what he saw in his telescope," said Paolo Galluzzi, director of the Museum of History and Science in Florence, the city where Galileo is buried.

Galileo, who lived from 1564 to 1642, is known to have had intermittent eye problems for the second half of his life and was totally blind for his last two years.

"There were periods when he saw very well and periods when he did not see very well," said Dr. Peter Watson, president of the Academia Ophthalmologica Internationalis and consultant to Addenbrooke's University Hospital, Cambridge.

Watson, who has studied Galileo's handwriting, letters, and portraits of the astronomer, suspects he may have had unilateral myopia, uveitis - an inflammation of the eye's middle layer - or a condition called creeping angle closure glaucoma.

Watson believes Galileo did not acquire eye problems by looking at the sun but by systemic illnesses, including an attack when he was young that left him temporarily deaf and caused bloody discharges and arthritis so severe he was bedridden for weeks.

He was under particular stress when he was tried for heresy by the Inquisition because the Copernican theory he supported conflicted with the Bible.

One of the "errors" that Galileo made, which Galluzzi suspects may have been attributed to his bad eyesight, is that he believed Saturn was not perfectly round but may have had an irregular, inflated side.

With his 20-power telescope and with his eyes in bad shape he might have mistaken Saturn's gaseous ring to surmise that it was formed of one planet with two moons as satellites.

"This was probably a combination of errors. He probably expected to find satellites and his eyesight may have contributed to some confusion," said Galluzzi.

Wednesday, April 16, 2008

Rosalind Franklin--Double Helix

Rosalind Franklin

I will say that wrongs will be righted and gender and ethnicity will finally dissolve in the sciences.

"Rosalind Franklin and the Double Helix"

Although she made essential contributions toward elucidating the structure of DNA, Rosalind Franklin is known to many only as seen through the distorting lens of James Watson's book, The Double Helix.

by

Lynne Osman Elkin

February 2003

American Institute of Physics

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 King'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.

The Tuscan landscape forms the background of this photograph of Rosalind Franklin, taken in the spring of 1950 by her friend Vittorio Luzzati. (Courtesy of Vittorio Luzzati.)

Franklin was born 25 July 1920 to Muriel Waley Franklin and merchant banker Ellis Franklin, both members of educated and socially conscious Jewish families. They were a close immediate family, prone to lively discussion and vigorous debates at which the politically liberal, logical, and determined Rosalind excelled: She would even argue with her assertive, conservative father. Early in life, Rosalind manifested the creativity and drive characteristic of the Franklin women, and some of the Waley women, who were expected to focus their education, talents, and skills on political, educational, and charitable forms of community service. It was thus surprising when young Rosalind expressed an early fascination with physics and chemistry classes at the academically rigorous St. Paul's Girls' School in London, and unusual that 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.

Coffee served in crucibles was a tradition in Jacques Mering's Paris laboratory, where Rosalind Franklin worked from 1947 to 1950. Biographer Anne Sayre reports that the time Franklin spent working in Paris was the happiest period of her life. This candid photo was taken by Vittorio Luzzati. (Courtesy of Vittorio Luzzati.)

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 l'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 1946­49, 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.

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. Many of the students there were evening students who worked during the day, and Franklin was impressed with their dedication. After the move to Birkbeck, she began her celebrated work with J. Desmond Bernal on RNA viruses like tobacco mosaic virus (TMV). She was a cautious scientist who began to trust her intuition more as she matured (see box 1 on page 45). 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.

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."1

Discovery of two forms for DNA

Franklin's most famous and controversial work yielded critical data that Watson and Crick used to determine DNA's structure. DNA is a double-helical molecule roughly in the form of a spiral staircase. The double-helical molecule, consisting of two unbranched polynucleotide chains, is best visualized by imagining it straightened into a ladder. The side rails of the ladder are each made up of alternating sugar and phosphate groups, linked by so-called 3' or 5' phosphodiester bonds. The sequence of the atoms in each rail runs in opposite directions, so the two sides of the molecular backbone are often described as antiparallel to each other. The rungs of the ladder consist of specific hydrogen-bonded horizontal pairs of nitrogenous bases that are attached to the deoxyribose sugars in the backbone's side rails. Birkbeck's Sven Furberg, who studied both the nucleoside and nucleotide of one of the bases, cytosine, in 1949, discovered that the base would be perpendicular to the sugar: The result can be extrapolated to hydrated DNA.2

The pairs of nitrogenous bases that make up the rungs are in the keto, as opposed to enol, tautomeric configurations. (The two are distinguished by the locations of hydrogen atoms available for hydrogen bonding.) The smaller single-ringed pyrimidines, cytosine (C) and thymine (T), are always paired with larger double-ringed purines, guanine (G) and adenine (A). Indeed, the consistent pairing of G with C and of A with T, as first proposed by Watson, explains the identical size of the ladder rungs and also Erwin Chargaff's 1952 observation that G and C (and likewise A and T) are always present in DNA in approximately equal amounts. The consistent pairings, along with the irregular linear vertical sequence of the bases, underlie DNA's genetic capacity.

In an experiment carried out shortly after she arrived at King's, Franklin identified two distinct configurations, called by her the A and B forms, in which DNA could exist. Her work, first presented in an internal King's seminar in November 1951 and published in Nature in 1953, was essential for determining the structure of DNA. Researchers working prior to Franklin's discovery invariably had to deal with confusing x-ray diffraction patterns that resulted from a mixture of the A and B forms.

The drier crystalline A form contains about 20% water by weight and is optimally produced at about 75% relative humidity. Cation (for example, Na+) bridges between ionized phosphates are probably responsible for intermolecular linking in the crystalline structure. The less ordered, fully hydrated, paracrystalline B form--typically the configuration that occurs in vivo--is obtained from the crystalline A form when DNA fibers absorb water in excess of 40% of their weight. Optimal production of the B form occurs at approximately 90% relative humidity. Extra hydration makes it easier for the molecule to assume the lowest-energy, helical configuration. It also keeps the two helical backbone chains farther apart than in the A form and elongates the molecule by about 30% until the B form appears with its bases oriented perpendicular to the fiber axis.

Franklin slowly and precisely hydrated then dehydrated her DNA sample to obtain her best pictures of the A form. To get her samples, though, she had to extract DNA fibers from a gel-like undenatured DNA sample that Wilkins had acquired from Rudolf Signer of the University of Berne in Switzerland. Franklin pulled exceptionally thin single fibers and controlled the humidity in her specimen chamber by bubbling hydrogen gas through salt solutions and then flooding the chamber with the humid gas that resulted. Franklin's PhD student, Raymond Gosling, told me that the chamber leaked so much hydrogen gas that he was afraid they would blow themselves up accidentally and take half of King's College with them.

Franklin's careful treatment during the transformation from crystalline A-form to hydrated B-form DNA resulted in such a drastic size change that, according to Gosling, the elongating specimen practically "leaped off the stage." After designing a tilting microfocus camera and developing a technique for improving the orientation of her DNA fibers in the camera's collimated beam, Franklin took x-ray diffraction photographs of the B form.

Franklin's B-form data, in conjunction with cylindrical Patterson map calculations that she had applied to her A-form data, allowed her to determine DNA's density, unit-cell size, and water content. With those data, Franklin proposed a double-helix structure with precise measurements for the diameter, the separation between each of the coaxial fibers along the fiber axis direction, and the pitch of the helix.3

The diffraction photograph of the B form of DNA taken by Rosalind Franklin in May 1952 was by far the best photograph of its kind. Data derived from this photograph were instrumental in allowing James Watson and Francis Crick to construct their Nobel Prize­winning model for DNA. (Courtesy of the Norman Collection on the History of Molecular Biology in Novato, Calif.)

The resolution of the B-form photograph #51 shown in figure 3 allowed Franklin to determine that each turn of the helix in the B form is 34 Å long and contains 10 base pairs separated by 3.4 Å each,3 in accordance with less precise data obtained by William Astbury and Florence Bell in 1938.4 Wilkins, photographing living sperm cells in 1952, obtained an X-shaped B-form diffraction pattern similar to Franklin's. Her photograph, though, showed much more detail.

Additional contributions


The cylindrical Patterson map calculations that Franklin applied to the A-form of DNA were the first such calculations applied to any molecule. They confirmed her suggestions that the hydrophilic sugar phosphates form the external backbone of the DNA molecule and that the hydrophobic base pairs are protected inside that backbone from the cell's aqueous environment. The calculations also allowed her to deduce that the A-form helix has two antiparallel chains (see figure 4d). With Gosling, Franklin provided details of the physical distortion accompanying the dehydration transformation from B-form to A-form DNA.5 She also showed that the bases of the A form are tilted and curved slightly, and that 11 pairs of bases are compacted within a repeat distance of 28.1 Å.

Notebook entries show that Rosalind Franklin (a) recognized that the B form of DNA was likely to have a two-chained helix; (b) was aware of the Chargaff ratios; (c) knew that most, if not all, of the nitrogenous bases in DNA were in the keto configuration (my circles indicate the hydrogen positions that distinguish the keto from the enol form); and (d) determined that the backbone chains of A-form DNA are antiparallel. (Courtesy of Anne Sayre and Jenifer Franklin Glynn.

In her section of the 1952 King's Medical Research Council (MRC) report, Franklin gave quantitative measurements for the interphosphate distances and discussed the external placement of the phosphates. Her presentation was instrumental in getting Watson and Crick to abandon their earlier attempts at placing the bases on the outside of their model. Initially, they (and Linus Pauling, too) mistakenly thought that the bases would have to be externally accessible in order to pass genetic information.

In May 1952, Franklin presented her clearest evidence of the helical backbone, with her diffraction photograph #51. Although she did not yet realize how the nitrogenous bases are paired or that the helical backbone rails of B-form DNA are antiparallel, her notebook entries starting in January 1951 clearly show that she was making significant progress toward solving those two final aspects of DNA structure. After reading an article by June Broomhead,6 and studying other related papers, she had used the keto configuration for at least three of the four bases. She was aware both of Jerry Donohue's work concerning tautomeric forms of bases and of Chargaff's work (see figure above).

Astbury and Bell's earlier, less clear diffraction photographs and later data of Wilkins suggested some of the data that Franklin derived from her photograph #51. But Franklin's results were much more precise than the Astbury and Bell data, which showed neither an X pattern nor layer lines. Astbury and Bell themselves described their results as "still rather obscure." After Oxford crystallographer Dorothy Hodgkin helped her to eliminate two of three possibilities she had calculated, Franklin described the correct crystallographic space group for DNA in the 1952 MRC report.

Only after Crick obtained Franklin's data--his thesis adviser, Max Perutz, agreed to give him a copy of the 1952 report and Watson had seen photograph #51--was he sufficiently convinced to start constructing the backbone of the successful DNA model. He recognized the similarity of the space group Franklin had calculated to that of his thesis molecule, hemoglobin, and immediately deduced that there would be an antiparallel orientation between the two DNA coaxial fibers. Within one week, he started modeling the correct backbone in a manner compatible with Franklin's data. On several occasions, Crick has acknowledged that the data and conclusions in the 1952 report were essential.

Franklin's 17 March 1953 draft

On 18 March 1953, Wilkins penned a letter acknowledging receipt of the Watson and Crick manuscript that described the structure of DNA. A day earlier, Franklin, who was preparing to leave for Birkbeck, polished an already written draft manuscript outlining her conclusions about the double-helix backbone chain of B-form DNA.7 Franklin only slightly modified her draft to prepare her April 1953 Nature paper, which appeared as the third in a series that led off with the famous Watson and Crick proposal. Partly as a consequence of its placement, Franklin's paper seemed merely to support Watson and Crick's work. But Franklin's data played far more than just a supporting role--as early as 1968, Watson's The Double Helix tells us so.

Ironically, despite its negative portrayal of Franklin, The Double Helix was what first brought widespread attention to Franklin's key contributions to the Watson and Crick proposal. The book describes how Watson and Crick built their first, and incorrect, model right after Watson inaccurately reported Franklin's November 1951 seminar data to Crick. It also details how, after 13 months of inactivity, they built their correct model once Wilkins showed Franklin's photograph #51 to Watson, and Perutz showed Crick the 1952 MRC report.

The importance of Franklin's work to the discovery of DNA structure has not been well documented until recently for a variety of reasons too long to discuss here. Relevant issues include women's being underrepresented in historical accounts, although several authors have striven to correct that imbalance;8 Watson and Crick's routinely citing the more senior Wilkins before Franklin; and Wilkins's repeating much of Franklin's work. In addition, Wilkins, not Franklin, was nominated for membership in the Royal Society even though, at the time of his nomination, Franklin was famous for her TMV accomplishments.

Conflict within the King's MRC

Franklin was an outstanding and accomplished scientist--a fascinating individual with a strong personality who made a lasting impression on almost everyone she met. Throughout her career, she routinely ate lunch amicably with both male and female colleagues and most of her acquaintances liked her. Her numerous lifelong friends thought her bright, fascinating, witty, and fun. Most of her lunchtime colleagues at King's would agree with that description, but only as it pertained to her lunchtime persona. When Rosalind headed for the laboratory, she shed almost every vestige of lightheartedness as she focused exclusively on her work.

Furthermore, in what amounted almost to social heresy in England, en route to her laboratory she typically bypassed the morning coffeepot and afternoon tea in favor of a direct assault on her work. Franklin was considered by King's colleagues to be "too French" in her dress, in her intellectual interests, and in her temperament. She was exceedingly direct, intent, and serious, with the tendency to leap into passionate debate. She could be assertive, uniquely stubborn, argumentative, and abrasive to the point that colleagues, especially Wilkins, sometimes found her unpleasant.

The Helix Funeral Invitation

Maurice Wilkins insisted that DNA was helical before there was clear evidence. That greatly annoyed Rosalind Franklin, as did so many things about him. Franklin was well aware that the x-ray diffraction photographs of the A form, unlike those of the B form, lacked the clear X-shaped pattern indicative of a helix. Instead, they displayed a detailed and confusing assortment of reflections that she could only interpret through the complicated and daunting procedure of cylindrical Patterson analysis. Therefore, when, over a period of about five months starting on 18 April 1952, Franklin recorded some misleading, apparently asymmetrical double orientation data in the A form, she got perverse pleasure out of possibly annoying Wilkins with her result. As a joke, she penned the "death of the helix" funeral invitation reproduced here. That she wrote the invitation is clearly substantiated in interviews with Raymond Gosling and Wilkins and in many other professional accounts.

The extent and significance of the distribution of the invitation is another matter. During interviews, only diffraction expert Alec Stokes said that he had received one. A few people said that they saw an invitation posted on a bulletin board, and most said that they had never even seen one. That testimony is incompatible with the often repeated claim that a multitude of these cards were sent out.

Historians Horace Judson and Robert Olby argued that the invitation indicated Franklin was antihelical, although Olby notes it was a joke as well.10,11 To the contrary: Franklin's student Raymond Gosling is adamant that Franklin considered the B form, with its striking x-ray pattern, to be helical. Examinations of Franklin's notebooks have led to the same conclusion, although it is also clear that, for a while, Franklin definitely had her doubts about the helicity of the A form.

On the rare occasions when Franklin departed from her typical behavior, King's colleagues usually did not even notice--they took her seriously at all times. That became especially important when she created a "death of the helix" funeral invitation as a joke after obtaining some data indicating that A-form DNA is nonhelical (see above).

Whereas Franklin was quick, intense, assertive, and directly confrontational, Wilkins was exceedingly shy, indirect, and slowly calculating to the point of appearing plodding. Almost all testimony from King's staff indicates that any blame for their perpetual conflict needs to be shared. John Randall, director of the MRC, also deserves some share of the blame. Without informing Wilkins, he wrote a letter to Franklin assigning DNA structural studies to her. He also did not warn Franklin about Wilkins's continuing interest in DNA.

Randall and Wilkins did make some important accommodations for Franklin. They hired her into a senior position based on her expertise. They gave her an excellent laboratory, the highest quality DNA, and a decent budget. However, numerous MRC women, although very well treated for that era, did not receive precisely equal treatment with men. Taken as a whole, the King's MRC women did not rank quite as highly as the men. Also, Gosling told me that women were not allowed upstairs for after-lunch coffee in the smoking room, "a wonderful long room," he explained, "with window seats." That exclusion undoubtedly cut off a natural route for easy scientific conversation.

Franklin's tenure at the MRC ended on an unfortunate note. As a condition to agreeing to transfer her fellowship to Birkbeck, Randall made Franklin promise not to perform additional experiments on DNA, or even to think about DNA. Moreover, Franklin was forced to leave her diffraction photograph behind at King's and to leave the work of confirming DNA's structure to Wilkins. Personality conflicts were the major source of Franklin's difficulty at King's, and her status as a woman may have made her problems worse. Even today, I and many of my women colleagues find that forcefully aggressive behavior, for example, is usually considered merely irritating when exhibited by a man but is often deemed unacceptable when demonstrated by a woman.

Watson's view: The Double Helix

In The Double Helix, Watson bases his account of Franklin on recollections of their three brief meetings between 1951 and 1953, and on repeated complaints about her from Wilkins. The "Rosy" that Watson describes is a caricature based on the more difficult aspects of Franklin's personality. His portrayal--a far cry from the competent scientist described by her colleagues or the fascinating person described by her friends--is an effective device for promoting the idea that Watson and Crick had to rescue DNA data from--as Watson's book puts it--this "belligerent" woman who could not "keep her emotions under control" and who did not know how to interpret her own data. Watson falsely depicts Franklin as Wilkins's assistant, incapable and unworthy of Nobel Prize­caliber work. His book was published against the vehement protest of key DNA participants, who were upset about its numerous inaccuracies.9

Unfortunately, Watson's admittedly fascinating, irreverent, and concise book has sold millions of copies and is for many, especially in the US, the primary source of information about DNA history. That such a one-sided account both is presented as historical fact and has had tremendous influence is worrisome. Watson's treatment of Franklin, who was then deceased and not protected by libel laws, is especially troublesome.

Watson's depiction of Franklin went largely unchallenged, at least in print, until Anne Sayre published her 1975 biography Rosalind Franklin and DNA (W. W. Norton, 1975). Sayre asked awkward, science-related questions: Why would Franklin give her data to Watson, Crick, and Wilkins, three scientists who seemed to have nothing to offer in return at that time? Where would Watson and Crick be without Franklin's results? Why did they not acknowledge Franklin's contributions clearly and appropriately? Regrettably, Sayre's influence was diminished because she was misled about the conditions for women at the MRC. She mistakenly assumed those conditions to be as problematic as they were at the rest of King's, and therefore incorrectly interpreted Franklin's problems at King's in terms of gender issues. Subsequent accounts, though in many ways excellent, typically are dismissive of gender concerns10 and personality issues.11 They don't address the awkward questions Sayre raises nor do they sufficiently emphasize that the Watson and Crick model was made possible by Franklin's data. Fortunately, Brenda Maddox's outstanding and comprehensive 2002 biography of Franklin12 does consider questions of acknowledgment and corrects misconceptions about gender and personality issues. Perhaps it will educate the public more fully than have previous texts. (See Physics Today, February 2003, page 61, for a review of Maddox's book.)

Inadequate acknowledgment

In their 1953 paper, Watson and Crick state that they had been "stimulated by a knowledge of the general nature of the unpublished experimental results and ideas of Dr. M. H. F. Wilkins, Dr. R. E. Franklin and their co-workers at King's College, London." That oblique acknowledgment misrepresented Franklin's role and, whatever its intention, left most people with the impression that her work mainly served to confirm that of Watson and Crick. It has to be one of the greatest understatements in the history of scientific writing.

Given her temper, it is likely that Franklin would have been very angry if she had known the extent to which Watson and Crick used her data. In a 1951 incident, Franklin was furious that a conference acquaintance planned on publishing an idea of hers without giving proper acknowledgment. She shocked him by the tone of her letter in which she demanded coauthorship.

In 1954, Crick and Watson published a detailed methods paper in the Proceedings of the Royal Society. In that paper, their acknowledgment of Franklin is often ambiguous. Three of the four times they mention the importance of her data, they link it with mention of Wilkins's data first in a way that suggests the two scientists' contributions were of equal importance. Twice they follow what appears to be a clear acknowledgment of Franklin's contributions with a recanting qualifying statement, for example, "we should at the same time mention that the details of [the King's College's] X-ray photographs were not shown to us and that the formulation of the structure was largely the result of extensive model building in which the main effort was to find any structure which was stereochemically feasible." They might not have known all of the details, but they had access to a significant number of them (see above).

Another lost opportunity for acknowledging Franklin occurred during the 1962 Nobel Prize ceremony. Neither Watson nor Crick thanked Franklin for making their discovery possible. Indeed, neither mentioned her name, although, according to Wilkins, Crick did ask him to mention Franklin. That request was a dubious shifting of responsibility given Wilkins's antipathy toward Franklin, and Wilkins in fact made only minor mention of her. Crick spoke on the genetic code, which had nothing to do with Franklin's work. Watson spoke on RNA, including RNA viruses. Franklin was an expert on those viruses, yet, in his 59 citations, Watson managed to omit any reference to her work. To this day, Watson emphasizes the opinion that Franklin, although a gifted experimentalist, could not properly interpret all of her own DNA data.

Franklin is prominent in virtually every telling of DNA history, but she is painted differently in various accounts. Watson and Crick made one of the most important and impressive scientific discoveries of the 20th century, but their golden helix is tarnished by the way they have treated Franklin and Wilkins. A meaningful gesture, given that it was Franklin's data that Watson and Crick most directly used, would be for scientists to refer to the "Watson, Crick, and Franklin structure for DNA."

It is important to stop demeaning Franklin's reputation, but equally important to avoid obscuring her more difficult personality traits. She should not be put on a pedestal as a symbol of the unfair treatment accorded to many women in science. Her complicated relationship with Wilkins has been treated in overly simplistic ways. Distorted accounts, which inaccurately portray the three Nobel Prize winners as well as Franklin, are unfortunate and unnecessary: There was enough glory in the work of the four to be shared by them all.


I thank Barbara Low, Mary Singleton, Martha Breed, Marilyn Goldfeather, and Paulina Miner for their many helpful editorial suggestions, and Richard Hasbrouck for his assistance in preparing figures.

Lynne Elkin is a professor of biological sciences at California State University, Hayward. She welcomes responses and inquiries about issues pertaining to the story of Rosalind Franklin and DNA structure.

References

1. J. D. Bernal, Nature 182, 154 (1958).

2. S. Furberg, Acta Crystallogr. 3, 325 (1950); Acta Chem. Scand. 6, 634 (1952).

3. These figures are quoted in Franklin's 1952 Medical Research Council report and her unpublished 17 March 1953 draft paper. The draft was discovered many years later and written about by A. Klug in Nature 219, 808 (1968); 219, 843 (1968); 248, 787 (1974).

4. W. T. Astbury, F. O. Bell, Nature 141, 747 (1938); Cold Spring Harb. Symp. Quant. Biol. 6, 112 (1938).

5. R. E. Franklin, R. G. Gosling, Acta Crystallogr. 6, 673 (1953); 6, 678 (1953).

6. J. Broomhead, Acta Crystallogr. 4, 92 (1951).

7. A. Klug, Nature 219, 808 (1968); 219, 843 (1968); 248, 787 (1974).

8. M. Bailey, American Women in Science: A Biographical Dictionary, ABC-CLIO, Santa Barbara, Calif. (1994); G. Kass-Simon, P. Farnes, eds., Women of Science: Righting the Record Indiana U. Press, Bloomington, Ind. (1990); M. B. Ogilvie, Women in Science: Antiquity Through the Nineteenth Century. A Biographical Dictionary With Annotated Bibliography, MIT Press, Cambridge, Mass. (1986); M. W. Rossiter, Women Scientists in America: Struggles and Strategies to 1940, Johns Hopkins U. Press, Baltimore, Md. (1982); M. W. Rossiter, Women Scientists in America: Before Affirmative Action, 1940­1972, Johns Hopkins U. Press, Baltimore, Md. (1995).

9. See for example, W. Sullivan in J. D. Watson's The Double Helix: A Personal Account of the Discovery of the Structure of DNA, Norton Critical Edition, G. S. Stent, ed., W. W. Norton, New York (1980). Copies of original letters are in the Norman Collection on the History of Molecular Biology in Novato, Calif.

10. F. H. Portugal, J. S. Cohen, A Century of DNA: A History of the Discovery of the Structure and Function of the Genetic Substance, MIT Press, Cambridge, Mass. (1977); H. F. Judson, The Eighth Day of Creation: Makers of the Revolution in Biology, CSHL Press, Plainview, N.Y. (1996).

11. R. C. Olby, The Path to the Double Helix: The Discovery of DNA, Dover, New York (1994).

12. B. Maddox, Rosalind Franklin: The Dark Lady of DNA, HarperCollins, New York (2002).

13. The original letter is in the Anne Sayre Collection of the Microbiological Society Archives at the University of Maryland, Baltimore County. See also ref. 12.

14. The original 5 March 1976 letter is in the Anne Sayre Collection of the Microbiological Society Archives at the University of Maryland, Baltimore County. See also ref. 12.

15. H. R. Wilson, Trends Biochem. Sci. 13, 275 (1988).


Monday, March 31, 2008

Boron vs carbon

Boron:

B
Atomic Number: 5
Atomic Mass: 10.811 amu
Melting Point: 2300.0 °C [2573.15 K, 4172.0 °F]
Boiling Point: 2550.0 °C [2823.15 K, 4622.0 °F]
Number of Protons/Electrons: 5
Number of Neutrons: 6
Classification: Metalloid
Crystal Structure: Rhombohedral
Density @ 293 K: 2.34 g/cm3
Color: Brownish
Number of Energy Levels: 2
First Energy Level: 2
Second Energy Level: 3
Isotopes: B-10, B-11
Date of Discovery: 1808
Discoverer: Sir Humphry Davy, J. L Gay-Lussac
Obtained From: Kernite

Carbon:

C
Atomic Number: 6
Atomic Mass: 12.0107 amu
Melting Point: 3500.0 °C [3773.15 K, 6332.0 °F]
Boiling Point: 4827.0 °C [5100.15 K, 8720.6 °F]
Number of Protons/Electrons: 6
Number of Neutrons: 6
Classification: Non-metal
Crystal Structure: Hexagonal
Density @ 293 K: 2.62 g/cm3
Color: Black
Number of Energy Levels: 2
First Energy Level: 2
Second Energy Level: 4
Isotopes: C-11 [20.3 minutes], C-12 [Stable], C-13 [Stable], C-14 [5730.0 years], C-15 [2.5 seconds]
Date of Discovery: Known to the ancients
Discoverer: Unknown

Gaze at the periodic table and look at all the elements and speculate why "carbon" is the basis for life as we experience it. What are the criteria for life to form? You look at the chart and wonder why carbon instead boron [ or even silicon and sulphur]. Boron is the nearest candidate but boron has problems of its own. But why just carbon? Several come to mind: The ability to have free electrons that can produce a variety of chemical bonds, the ability to replicate with DNA/RNA, and its abundance. It is quite unique that carbon has a fine chemical relationship with hydrogen, oxygen, nitrogen, phosphorus, calcium, and sulfur. The replication feature is characteristic of DNA/RNA molecules called "Linear Polymeric Molecules" and it is these molecules that are composed of simple to complex combinations of hydrogen, oxygen, nitrogen, phosphorus, calcium, and sulfur. [To note: Trace elements are also employed such as zinc, molybdenum, selenium and the biggies like sodium, potassium, and iron.] Carbon's nearest neighbor, boron, can to some degree display similar molecules but is a bit erratic in that the number of chemical bonds varies from three to six [the same for silicon and sulphur]--not predictable enough to perform replication whereas carbon bonding is always four and very reproducible. And lastly, boron for example is just not that abundant. It looks like that the chemical characteristics fill the criteria for the evolution of life.

The observation of the periodic table and a bit of cosmology yields knowledge, mystery, and awe. Just think about it...when a star is being consumed by the physics and the available elements of the star it basically stops at iron, the star bursts, and, wow, here come the other elements--one right after another. But why was carbon elected as the source for life as we know it. Well, I did offer some explanation above but it remains that it is curious that just one, just one, element was given the task. But then again, we simply don't know about life throughout the universe and some soul a billion light years away is asking: "Why is our life system based on an element with an atomic weight of 10.82?" We may want to believe that carbon-based life is universal and disappointed if we discover a multiplicity of bases.