One sentence. Her hard work was STOLEN and they gave her one friggin sentence in the acknowledgement section. Meanwhile they’re riding the cash cow to fame and glory, heralded as these biological geniuses.
It seems like textbooks have become more progressive in the past 5 years or so, but the biology textbook I was issued in high school (published in the early 2000s) dedicated a small, 2-3 sentence paragraph to Rosalind Franklin (which mostly focused on explaining what X-ray crystallography was, not focusing on her contribution or Watson and Crick’s theft of her experimental data), while Watson and Crick received an entire full page spread with their iconic photograph, posing next to a giant DNA model. The most recent version of that textbook now has an entire page dedicated to Rosalind and even includes a picture of her, though!
(Pierce, B. 2012. Genetics: A Conceptual Approach. 4th ed.)
Watson and Crick took credit for Franklin’s work and got away with it because she was a woman. She couldn’t even be awarded the Nobel prize because she died as a result of the radiation from the very X-ray diffraction techniques she used to discover the structure of DNA. Women were not taken seriously in science back then and even still today there is a huge deficit of females in STEM fields.
On February 21, 1953, Francis Crick and James Watson discovered the structure of deoxyribonucleic acid (DNA) using unacknowledged photographs and research by their colleague Rosalind Franklin. They had considered many other candidates for the structure, including single and triple strand helices before deciphering the structure. Franklin’s x-ray crystallography (image below)
would provide the missing essential clue they needed to decipher the structure. They would publish a paper that same year describing their discovery, but the significance of the discovery was largely overlooked by the general public for over a year. Today it stands as one of the most remarkable milestones in the history of science.
The word deoxyribonucleic is a compound word formed around the main root word ribose, which arrived in English in 1892 via the German word Ribose which was itself borrowed from the English word of 1880 arabinose, a sugar derived from gum arabic. The word nucleic comes from the Latin word nucleus meaning a kernel around 1700, from the Latin diminutive nucula meaning a little nut. It did not take the meaning of a central characteristic or attribute until 1762. It wasn’t applied to cellular structures for another 70 years around 1862. The -oxy- root comes from the Ancient Greek word οξυς (oxys) meaning sharp or pointed (sharing the earlier common root word that gave the Latin word acer with the same meaning and ultimately the English word acid). The de- prefix is a Latin preposition meaning down from, off or away from, used mainly in English compound words as a privative, meaning that something lacks something.
Hey, first off, I love your blog. Additionally, how do you think Medic would respond to the discovery of DNAs structure? Watson and Crick created the model in 1953, which quasi fits in with his timeline.
Well, obviously that would be really exciting to anyone in medical research during that time! However, I like to think that he’d want the contributions of Rosalind Franklin to be recognized alongside Watson and Crick, seeing as her data was critical to their success and glossed over for decades after.
If not for Franklin’s expertise in X-ray crystallography, Watson and Crick might never have clued into the double helix model. At one point, they were told to not even bother with their DNA research because their models were so off! I think Medic would’ve identified with a determined individual researcher like Rosalind Franklin.
Not that she would’ve been able to collect the Nobel Prize she deserved, anyway, since she died of ovarian cancer in 1958, four years before Watson and Crick got the honor. (The Nobel Foundation doesn’t award people posthumously.) Not that accolades are the most important thing. It’s just not fair.
An English chemist whose work with x-ray crystallography was instrumental to discovering the structures of DNA, viruses, coal, and graphite; she died of breast cancer before she could be awarded the Nobel prize, and her colleagues Watson and Crick are often given sole credit to this day
Dorothy Hodgkin was a Nobel Prize winner who developed the
technique of protein crystallography, confirmed the structure of penicillin and
vitamin B12, was generally the pioneering figure in the field of X-ray
crystallography of biological molecules. Even cooler, she taught Prime Minister
Margaret Thatcher (who had a BS in Chemistry from Oxford).
((at least 3 important science & medicine people born on May 12))
Ok so some of you remember the crystallization stuff from my field study that I posted
Well it turns out today I got to take a much closer look at
the crystals I made and shoot them through the X-ray machine.
So here’s one of the tubes with the MANY crystals of hemoglobin
(with the drug). I showed you something like that last week.
I got to use the microscope to look at them up close and pick a good enough crystal to shoot through the X-ray diffraction machine.
LOOK AT HOW FUCKING BEAUTIFUL THEY ARE
So the crystal we picked went under a glycerin/mother liquor solution to protect it from breaking down. (Below: the crystals on the left, the solution on the right, and the original mother liquor is behind the solution)
Mother liquor is the liquid leftover after a crystallization btw.
So the crystal was picked up with a really tiny “lasso” tool so it could be hooked up onto the X-ray machine.
That tiny, pointy thing has a REALLY small hoop at the tip of it to pick the crystal up.
here’s a pic of it up close; that’s how small the hoop and crystal is
and this is the X-ray diffraction machine.
The crystal is held up here:
and this “shoots” towards the crystal which lets it’s X-rays scatter and that gives us information on the crystalline structure. That ultimately lets us know about the structure of the individual molecules.
Here’s an up close look at the crystal that was picked:
That’s after it was mounted on the X-ray machine. It’s hard to see cause it’s in front of the black screen.
and that’s the “X-ray” of the crystal we got. The individual dots are the individual components of the crystal. (We actually diffracted a second crystal to get a better x-ray because the dots were too close together on this one). This basically lets us see each unit cell of the crystal itself which would contain a repeat of the hemoglobin molecule with the drug/compound in this case.
By next week, I’ll be able to take a look at the actual protein structure of the Hb molecule and the drug and see how they bind together.
The plan was to grow a single crystal from this compound for a single crystal X-ray crystallographic analysis to know the exact structure of the compound. But sadly it only gave these fluffy needle like crystals from every solvent what could be used for it’s crystallization.
Hodgkin (1910-1994) was a British chemist who in 1964 won the Nobel Prize for
her development of protein crystallography. She advanced a technique used to
determine the three-dimensional structure of molecules, and confirmed the
structures of penicillin and of the vitamin B12.
She is seen as a pioneer in the field of X-ray crystallography, and her
extensive work led to a better understanding of the structure of biological
molecules. Years after winning the Nobel, she was also able to decipher the
structure of insulin.
In Rosalind Franklin's crystallography experiment, how did the DNA strand not get destroyed by the high energy X-rays used?
I worked with crystallographers for like seven years, and I’m still convinced it’s 95% magic.
In x-ray crystallography experiments, you don’t shine the x-ray beam on one single DNA strand, or protein, or whatever it is you’re looking at. One DNA strand would certainly be obliterated by the beam, but not necessarily the crystal (although, often, the x-ray does annihilate your sample. That’s why you need more than one, which makes it even harder).
Instead of a single molecule, it’s a solid crystal, precipitated out of a complex solution of sometimes more than a dozen chemicals, with each crystal made of bajillions and bajillions of individual molecules arranged in an organized lattice. Different crystal structures, whether they are cubes, or tetrahedrons, or hexagonal pyramidal pentaglobs, will act differently in the beam. You don’t know in advance what you’re gonna get.
The protein crystals we used to look at back in my Ph.D. lab looked a lot like this:
Actually, if we’re being honest, they usually didn’t look like that. This is the sort of crystal you dream of. Most things aren’t quite this tidy when they crystallize.
When the x-ray beam is directed at the crystal, it diffracts (bounces off of) any atoms in its way. But x-rays have super-short wavelengths, and molecules are mostly empty space, so only a small fraction of the x-ray waves encounter an atom to bounce off of.
It’s the sum of ALL the rare bouncing events, in the entire crystal, organized into its repeating, ordered structure, that creates the x-ray dot pattern. Then the real fun begins, which as any x-ray crystallographer (and I am not one) will tell you, involves lots of math, and a fair bit of magic.
//Yo Yo guys, I just started a new blog dedicated to my crystallography, so please check it out and give it a follow for some beautiful and interesting chemistry! I will try to link it below. Fingers crossed, i’m not good at formatting posts. This shot is an early shot of one of Macke’s copper sulfate crystal clusters! Now a single crystal has been grown to a length of around 7-8cm. She has talent that girl and its a pleasure to work with her.//
In 1915 he shared a Nobel Prize with his son for their work on X-ray crystallography. X-ray crystallography is the process of firing a beam X-rays at crystals, and detecting the pattern that emerges at the other end.
These diffraction patterns formed by the crystals splitting the beams show the atomic structure of the crystals themselves, and the discovery of this method was one of the greatest innovations ever achieved in science. Here’s why it’s all so important:
Uncovering the 3D structure of a key neuroreceptor
Neurons are the cells of our brain, spinal cord, and overall nervous system. They form complex networks to communicate with each other through electrical signals that are generated by chemicals. These chemicals bind to structures on the surface of neurons that are called neuroreceptors, opening or closing electrical pathways that allow transmission of the signal from neuron to neuron. One neuroreceptor, called 5HT3-R, is involved in conditions like chemotherapy-induced nausea, anxiety, and various neurological disorders such as schizophrenia. Despite its clinical importance, the exact way that 5HT3-R works has been elusive because its complexity has prevented scientists from determining its three-dimensional structure. Publishing in Nature, EPFL researchers have now uncovered for the first time the 3D structure of 5HT3-R, opening the way to understanding other neuroreceptors as well.
Neuroreceptors: structure and function Communication between the neurons of our body is mediated by neuroreceptors that are embedded across the cell membrane of each neuron. Neuronal communication begins when a neuron releases a small molecule, called a ‘neurotransmitter’, onto a neighboring neuron, where it is identified by its specific neuroreceptor and binds to it. The neurotransmitter causes the neuroreceptor to open an electrically conducting channel, which allows the passage of electrical charge across the neuron’s membrane. The membrane then becomes electrically conducting for a fraction of a millisecond, generating an electrical pulse that travels across the neuron. The family of neuroreceptors that work in this way is widespread across the nervous system, and is referred to as the “ligand-gated channel” family.
The mystery is how the binding of the neurotransmitter can induce the opening of an electrical channel to transport a signal into the neuron. The understanding of these molecular machines is of great medical importance, especially since neuroreceptors are involved in many neurological diseases. Currently, none of the mammalian ligand-gated channel neuroreceptors have been structurally described, which significantly limits our understanding of their function on a molecular level.
Uncovering the structure of 5HT3-R The team of Horst Vogel at EPFL has used X-ray crystallography to determine the 3D structure of a representative ligand-gated channel neuroreceptor, the type-3 serotonin receptor (5HT3-R). This neuroreceptor recognizes the neurotransmitter serotonin and opens a transmembrane channel that allows electrical signals to enter certain neurons. The 5HT3 receptor was grown in and then isolated from human cell cultures, and finally crystallized.
But before obtaining the 5HT3-R crystals, the EPFL team had to overcome a number of challenges. First, the relatively large size of the membrane-embedded 5HT3-R, like that of other similar channel neuroreceptors, makes it notoriously difficult to purify in sufficient quality and quantity. After years of painstaking work, the EPFL scientists succeeded in obtaining a few milligrams of 5HT3-R, which was still not enough to grow crystals using conventional methods.
Still, the crystal quality was insufficient. To address this, Vogel’s team used small antibodies, so-called nanobodies, which were obtained from llamas after the animals were injected with purified 5HT3-R. From a large library of isolated nanobodies, a particular one was found to form a stable complex with the 5HT3-R, and this complex eventually yielded crystals of exceptional quality.
After this, the procedure was straightforward: The crystals for X-ray crystallography were investigated at the synchrotron facilities at the Paul Scherrer Institut in Villigen and the European facilities in Grenoble. In this well-established technique, the crystals diffract X-rays in a characteristic pattern from which the 3D structure can be reconstructed.
The X-ray diffraction experiments yielded the 3D structure of 5HT3-R at an unprecedented resolution of 3.5 Ångstroms (3.5 millionths of a millimeter). The resulting 3D image shows a bullet-shaped 5HT3 receptor with its five subunits symmetrically arranged around a central water-filled channel that traverses the neuron’s cell membrane. The channel can adopt two states: a closed, electrically non-conducting state or, after binding a neurotransmitter, an open, electrically conducting state that allows the flow of electrical charges in and out of the neuron to generate an electrical signal.
“We have now elucidated the molecular anatomy of a receptor that plays a central role in neuronal transmission,” says Horst Vogel. “It is the first 3D structure of its kind and may serve as a blueprint for the other receptors of this family. In the next step, we have to improve the resolution of the structure, which might give us information on how to design novel medicines that influence this neuroreceptor’s function.”