Rosalind Franklin the Scientist

This month marks the centenary of the birth of Rosalind Elsie Franklin, who was
born in Notting Hill, London, on July 25, 1920. Her experimental studies on the
structure of DNA gave rise to the double helix in the early weeks of 1953, even
though her contributions were barely acknowledged at the time and her character
tarnished 15 years later in Jim Watson’s chauvinistic bestseller, The Double Helix.
Thankfully, Franklin’s pivotal role in the double helix drama has been restored,
helped along the way by Life Story, a superb 1987 BBC film (starring a young Jeff
Goldblum and a brilliant Juliet Stevenson), and a nuanced biography by the late
Brenda Maddox, Rosalind Franklin: The Dark Lady of DNA, who countered the
perception that Franklin was the doomed “Sylvia Plath of molecular biology.” In
2015, the Australian star Nicole Kidman, the daughter of a biochemist, portrayed
Franklin to critical acclaim on London’s West End in Photograph 51. The title of
that play comes from Franklin’s most famous experiment. In May 1952, working with
her student Raymond Gosling in a cellar laboratory at King’s College London (KCL),
she captured a magnificent X-ray photograph of stretched DNA fibers in the B, or
wet form. (The DNA was supplied by Swiss biochemist Rudolf Signer.) The image was
an unmistakable “X” configuration, but Franklin, more interested in the more
detailed pictures derived from the A form of DNA, filed it away. In so doing, she
also cast aside the notion that DNA was a helix. Franklin was deeply unhappy at
KCL, not so much because she was a woman in a man’s world but because, as Maddox
observed, “a wealthy Anglo-Jew felt out of place in a Church of England setting
dominated by swirling cassocks and students studying for the priesthood.” She
showed particular disdain for her KCL colleague Maurice Wilkins, a potential ally
and collaborator. Toward the end of 1952, she was ready for a fresh start in the
“nonsectarian” setting of Birkbeck College. Meanwhile, in Cambridge, Francis Crick
and Jim Watson had been prohibited from building models of DNA after a disastrous
first attempt in 1951 involving triple chains was embarrassingly torn apart (not
literally) by Franklin during a quick daytrip to the Cavendish Laboratory. But a
year later, with the great Linus Pauling entering the race, the duo persuaded their
boss, Sir Lawrence Bragg, to let them have another crack. An X-ray diffraction
image of DNA taken by Rosalind Franklin and her student Raymond Gosling in 1952.
This image, which provided crucial evidence of DNA’s double helical structure, is
known as Photo 51—a remarkably ordinary name for an image that has achieved iconic
status. Two priceless pieces of information, both sourced from Franklin without her
knowledge, were critical to the assembly. First, Wilkins showed Watson a copy of
Franklin’s Photo 51 in late January 1953. (With Franklin preparing to leave KCL,
Gosling had recently handed Wilkins the photo almost as a souvenir.) “My mouth fell
open and my pulse began to race,” Watson recalled. Although not a trained
crystallographer, he had learned enough to know that “X” marked a helix—probably a
double. “Even though [Crick] was a physicist,”  Watson memorably wrote, “he knew
that important biological objects come in pairs.” A short time later, Crick and
Watson’s colleague Max Perutz shared a copy of a Medical Research Council report on
the KCL biophysics department that he had received in mid-December 1952. It
included Franklin’s precise measurements of the B form, including key evidence that
the helices ran in opposite directions. Nothing was stolen—the MRC report was not
marked confidential—but nor did anyone at the Cavendish inform or consult Franklin
about the model building that was now ramping up in earnest using her data. (After
publication of The Double Helix, Watson apologized for any impression in the book
that Perutz had acted inappropriately.) Crick and Watson’s DNA jigsaw was completed
with assists from several other sources, including Erwin Chargaff’s curious
observation of a 1:1 ratio of certain bases and Jerry Donohue’s insight on the
correct chemical isoforms that proved the clincher. And then there’s William
Astbury, who had provided evidence for the stacking arrangement of bases, but did
not grasp the significance of his own student’s B-form X-ray image with the
trademark “X” pattern captured a full year before Franklin. Watson found the two
matching base pairs—A binds to T, C to G, big meets small—on a Saturday morning,
February 1953, before enjoying a pub lunch with Crick at The Eagle. Invited back up
to Cambridge to view the new two-chain model, Franklin understood immediately that
it must be more-or-less correct, even if she didn’t realize just how much Crick and
Watson had relied on her data. Crick and Watson offered token thanks to Franklin in
a footnote to their Nature paper that conceded a “general knowledge” of her
unpublished results. Things might have been different if the papers had crossed the
desk of the late Sir John Maddox, Brenda’s husband and editor emeritus of Nature,
who first took the reins of the journal in 1966. Far from “a general knowledge,”
Maddox said, “in fact, they had particular knowledge of her work, and I, as an
editor, would have smelled a rat at that.” Indeed, he might have insisted that
Franklin be credited as a co-author. Arrangements were made for Franklin and
Wilkins to publish their data separately in the same issue of Nature alongside the
double helix. Franklin and Gosling’s paper included the now-iconic Photo 51 but
ironically no mention of DNA—instead it was sodium thymonucleate. Franklin stated
cautiously that the genetic material was “probably helical,” with the phosphate
chain on the outside. Appearing as the third article, Franklin’s paper gave the
mistaken impression of being a confirmatory study instead of supplying the crucial
primary data. Shortly before publication, she inserted a sentence: “Thus our
general ideas are not inconsistent with the model proposed by Watson and Crick in
the preceding communication.” Well of course they weren’t—the double helix model
sprung from her data! If Franklin felt robbed or was upset by losing the race, she
never let on. She became friends with Crick and Watson, staying with the Cricks in
Cambridge before her death in 1958 of ovarian cancer (likely triggered by her
prolonged exposure to X-rays). As Brenda Maddox said: “She was cheated of the only
thing she really wanted, which was the chance to finish her work… Her lost prize
was life.” As former colleagues have insisted, Franklin would surely have deduced
the structure of DNA herself. Crick and Watson both felt Franklin’s biggest
disadvantage was that she didn’t have anyone at KCL to talk to. Her death robbed
her of a share of the Nobel Prize in 1962; instead, it was Wilkins who was honored
alongside Crick and Watson. Rosalind Franklin[Science History Images / Alamy Stock
Photo] Watson was widely criticized for his portrayal of Franklin in The Double
Helix but found support from an unexpected source. “As Franklin’s biographer, my
answer to critics is that if it weren’t for Watson, no one would have heard of
Rosalind Franklin,” Brenda Maddox concluded. In the last few years of her life,
Franklin did superb work on the structure of tobacco mosaic virus. Franklin was
laid to rest at a synagogue a few miles north of her birthplace. Her epitaph reads:
“SCIENTIST: Her research and discoveries on viruses remain of lasting benefit to
mankind.” Her name lives on with a university, a research institute, and many
halls, prizes, and societies named in her honor, as well as a Mars rover. The
legacy of the “dark lady”—for women in science and the unbridled love of doing
science—will shine brightly for centuries to come.

Watson and Crick describe structure of DNA

Watson and Crick describe structure of DNA1953Photo: Model of DNA molecule In the
late nineteenth century, a German biochemist found the nucleic acids, long-chain
polymers of nucleotides, were made up of sugar, phosphoric acid, and several
nitrogen-containing bases. Later it was found that the sugar in nucleic acid can be
ribose or deoxyribose, giving two forms: RNA and DNA. In 1943, American Oswald
Avery proved that DNA carries genetic information. He even suggested DNA might
actually be the gene. Most people at the time thought the gene would be protein,
not nucleic acid, but by the late 1940s, DNA was largely accepted as the genetic
molecule. Scientists still needed to figure out this molecule's structure to be
sure, and to understand how it worked. In 1948, Linus Pauling discovered that many
proteins take the shape of an alpha helix, spiraled like a spring coil. In 1950,
biochemist Erwin Chargaff found that the arrangement of nitrogen bases in DNA
varied widely, but the amount of certain bases always occurred in a one-to-one
ratio. These discoveries were an important foundation for the later description of
DNA. In the early 1950s, the race to discover DNA was on. At Cambridge University,
graduate student Francis Crick and research fellow James Watson (b. 1928) had
become interested, impressed especially by Pauling's work. Meanwhile at King's
College in London, Maurice Wilkins (b. 1916) and Rosalind Franklin were also
studying DNA. The Cambridge team's approach was to make physical models to narrow
down the possibilities and eventually create an accurate picture of the molecule.
The King's team took an experimental approach, looking particularly at x-ray
diffraction images of DNA. In 1951, Watson attended a lecture by Franklin on her
work to date. She had found that DNA can exist in two forms, depending on the
relative humidity in the surrounding air. This had helped her deduce that the
phosphate part of the molecule was on the outside. Watson returned to Cambridge
with a rather muddy recollection of the facts Franklin had presented, though
clearly critical of her lecture style and personal appearance. Based on this
information, Watson and Crick made a failed model. It caused the head of their unit
to tell them to stop DNA research. But the subject just kept coming up. Franklin,
working mostly alone, found that her x-ray diffractions showed that the "wet" form
of DNA (in the higher humidity) had all the characteristics of a helix. She
suspected that all DNA was helical but did not want to announce this finding until
she had sufficient evidence on the other form as well. Wilkins was frustrated. In
January, 1953, he showed Franklin's results to Watson, apparently without her
knowledge or consent. Crick later admitted, "I'm afraid we always used to adopt --
let's say, a patronizing attitude towards her." Watson and Crick took a crucial
conceptual step, suggesting the molecule was made of two chains of nucleotides,
each in a helix as Franklin had found, but one going up and the other going down.
Crick had just learned of Chargaff's findings about base pairs in the summer of
1952. He added that to the model, so that matching base pairs interlocked in the
middle of the double helix to keep the distance between the chains constant. Watson
and Crick showed that each strand of the DNA molecule was a template for the other.
During cell division the two strands separate and on each strand a new "other half"
is built, just like the one before. This way DNA can reproduce itself without
changing its structure -- except for occasional errors, or mutations. The structure
so perfectly fit the experimental data that it was almost immediately accepted.
DNA's discovery has been called the most important biological work of the last 100
years, and the field it opened may be the scientific frontier for the next 100. By
1962, when Watson, Crick, and Wilkins won the Nobel Prize for physiology/medicine,
Franklin had died. The Nobel Prize only goes to living recipients, and can only be
shared among three winners. Were she alive, would she have been included in the
prize? Related Features

'Pregnancy test for water' delivers fast, easy results on water quality

A new platform technology can assess water safety and quality with just a single
drop and a few minutes. Likened to a pregnancy test, the handheld platform uses one
sample to provide an easy-to-read positive or negative result. When the test
detects a contaminant exceeding the EPA's standards, it glows green. Led by
researchers at Northwestern University, the tests can sense 17 different
contaminants, including toxic metals such as lead and copper, pharmaceuticals,
cosmetics and cleaning products. The platform—which is powered by cell-free
synthetic biology—is so flexible that researchers can continually update it to
sense more pollutants. "Current water tests rely on a centralized laboratory that
contains really expensive equipment and requires expertise to operate," said
Northwestern's Julius Lucks, who led the study. "Sending in a sample can cost up to
$150 and take several weeks to get results. We're offering a technology that
enables anyone to directly test their own water and know if they have contamination
within minutes. It's so simple to use that we can put it into the hands of the
people who need it most." The research will be published on July 6 in the journal
Nature Biotechnology. Lucks is a professor of chemical and biological engineering
in Northwestern's McCormick School of Engineering and a member of the Center for
Synthetic Biology. Jaeyoung Jung and Khalid Alam, members of Lucks' laboratory, are
co-first authors of the paper. Molecular 'taste buds' A major challenge of ensuring
water quality is that people typically can't see or taste contaminants.
Northwestern's platform uses synthetic biology to sense this unnoticeable
contamination, filling in the gaps where human senses fall short. In cell-free
synthetic biology, researchers take the molecular machinery—including DNA, RNA and
proteins—out of cells, and then reprogram that machinery to perform new tasks. The
idea is akin to opening the hood of the car and removing the engine, which allows
researchers to use the engine for different purposes, free from the constraints of
the car. In this case, Lucks' team used molecular machinery from bacterial cells.
"Nature has already solved this problem," Alam said. "Biology has spent over three
billion years evolving an elegant solution to detect contaminants." "We found out
how bacteria naturally taste things in their water," Lucks added. "They do so with
little molecular-level 'taste buds'. Cell-free synthetic biology allows us to take
those little molecular taste buds out and put them into a test tube. We can then
're-wire' them up to produce a visual signal. It glows to let the user quickly and
easily see if there's a contaminant in their water." These reprogramed "taste buds"
are freeze-dried to become shelf-stable and put into test tubes. Adding a drop of
water to the tube—and then flicking it—sets off a chemical reaction that causes the
freeze-dried pellet to glow in the presence of a contaminant. "The magic is in the
tubes," Lucks said. "We compose everything and freeze dry it—the same process as
making astronaut ice cream." Inspired by women in science Lucks and his team call
this testing platform "RNA output sensors activated by ligand induction." But his
team has nicknamed it ROSALIND for short, in honor of famed chemist Rosalind
Franklin, who discovered the DNA double helix alongside James Watson and Francis
Crick. Franklin's 100th birthday would have been next month (July 25). "Her work
essentially eventually enabled us to learn how to reprogram DNA to act in our
technology," Lucks said. Professor Julius Lucks explains how to use ROSALIND.
Credit: Northwestern University When starting this project, Lucks took inspiration
from another woman scientist in his life: his wife, Northwestern anthropologist
Sera Young, who studies global food and water security and the role of household
water insecurity in societal well-being. "Sera researches how poor water quality
impacts people's daily lives," Lucks said. "People tend to go to the most
convenient sources to get water. But if they knew that water was contaminated, they
might choose to travel farther to find safer water. We want everyone to have the
tools they need in order to make informed decisions." ROSALIND in Paradise To test
the new platform in the field, Lucks, Jung, Alam and fellow Northwestern professor
Jean-Francois Gaillard visited Paradise, California at the end of last year. One
year earlier, a string of massive wildfires obliterated the northern California
town, destroying nearly 19,000 buildings and displacing most of its population.
Gaillard, a professor of environmental engineering, is an expert in the
biogeochemical processes that affect metals in the aquatic system. "Wildfires
basically melted the town," Lucks said. "They burned down buildings and melted cars
that released toxic metals into the environment." Lucks, Gaillard and their teams
tested ROSALIND alongside gold-standard water tests and discovered that ROSALIND
was able to identify the presence of elevated toxic metals in the water supply. It
also provided much faster and less expensive results. Lucks and his team envision
that ROSALIND could help recovery efforts like the one in Paradise, in which
residents needed to perform tens of thousands of tests in order to know if their
community was safe to re-enter. "Laboratory testing doesn't scale," Alam said. "It
shouldn't take days to get an answer to the simple question: 'Is my water safe to
drink?'" Difficulties of testing at home Disasters, of course, aren't the only
causes of unsafe water. Heavy metals, such as copper and lead, that are naturally
found in the environment can leech into pipes, contaminating household water taps
and school drinking fountains. Personal care products, such as sunscreens and
lotions, wash off people's skin and end up in waterways. Unused pharmaceuticals and
agricultural herbicides, too, run off into our water and end up in our sinks. But,
unless we can directly—and regularly—test for these pollutants, there's no way to
maintain a peace of mind. When testing water in their own home in Evanston,
Illinois, Lucks and Young noted several difficulties. Consuming high levels of
copper over many months or years can lead to liver damage and even death. With this
concern, Lucks decided to check the copper levels in their household water. It cost
$150 and took a month to receive the results. "This is a one-time test," Lucks
said. "It doesn't allow for checking levels from different taps in the house or
temporal testing over time." Testing for lead wasn't much easier. Lead-testing kits
are available at most hardware stores. But after filling a tube with water, it
still must be mailed to a centralized facility. It still costs up to $150 per test
and takes weeks for results. And if people want to check their water for other
contaminants, such as antibiotics, tests simply do not exist for consumers. "There
has been a lot of advances in developing point-of-use diagnostics for monitoring
pathogens," Jung said. "But not nearly enough effort for detecting chemical
contaminants." "To ensure access to safe and clean drinking water, we need
technologies that will allow easy monitoring of water quality," Lucks said. "With a
simple, easy-to-use, handheld device like ROSALIND, you can test the water in your
home or out in the field—where you would want to use it most." More information:
Cell-free biosensors for rapid detection of water contaminants, Nature
Biotechnology (2020). DOI: 10.1038/s41587-020-0571-7 ,
www.nature.com/articles/s41587-020-0571-7 Citation: 'Pregnancy test for water'
delivers fast, easy results on water quality (2020, July 6) retrieved 6 July 2020
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