Happy International Women’s Day! Many many many female scientists have contributed to the scientific odyssey I’ve been taking you through – I don’t have room to honor them all, but here are a few…

I’ve been trying to come up with a way to honor today, but it was too hard to just choose just one woman to feature, so I decided – why choose? Instead, in today’s post, I’m going to highlight some of the female scientists that I’ve encountered throughout my research for these posts. There’s not room for everyone, and there’s not even enough room in a single post to do any of the few I’ve chosen what they’re due. But I’m going to do my best – in today’s post I highlight key contributions and a little about them. And provide links (at the bottom) to where they’ve shown up in my posts so you can read more about them.

Even though they may not be as prominent in the history books (for reasons including not being given the opportunity to participate, being discriminated against when they did, being restricted to “lower” positions, and being left out of retellings) women have played crucial roles in the history of biochemistry and to them we owe much of what we know. From slighted superstars like Rosalind Franklin (of DNA double-helix fame) to lesser-known names like Ilona Banga, who co-discovered the proteins that make muscles move, there are so many female scientists I love. Some, like x-ray crystallography pioneer Dorothy Crowfoot Hodgkin “made it big,” being honored with Nobel Prizes, while others have been left out of the credit-giving (major side-eye to Alfred Hershey for not even mentioning Martha Chase in his Nobel acceptance speech based largely on experiments they did together to help show that DNA, not protein, transmits genetic information). 

Instagram only letting you post 10 pics forced me to narrow down my honorees, so today I decided to feature: Dorothy Crowfoot Hodgkin, Barbara Low, Janet Litster Rideout, Martha Chase, Rosalind Franklin, Eileen Southgate, Ilona Banga, Sylvey Kornberg, and Maud Menten.

Some structural superwomen. Structural biology is a field that is interested in what biological molecules such as proteins look like at the atomic scale (i.e. how all the individual carbons, oxygens, etc. are linked together in 3D) and how what they look like (their structure) allows them to carry out their various functions. One of the main techniques that structural biologists use is x-ray crystallography, which involves beaming x-rays at crystalline arrangements of molecules -> the molecules scatter the x-rays -> the scattered rays interact with one another & hit a detector and get recorded as a pattern of spots (diffraction pattern) -> scientists work backwards from the spots to figure out where the scattering points were and use this to figure out where the atoms in the molecule are. 

That’s a major oversimplification of the technique. For more detail: http://bit.ly/xraycrystallographyresEven these days, it isn’t simple (speaking from experience…) and that’s with powerful equipment, software, and COMPUTERS doing all the complicated calculations. Imagine doing it without computers and having to figure out what math you even needed to do! This was the situation faced by early crystallography pioneers, many of whom were women, and one of whom is rightly hailed as a true leader in the development of the use of x-ray crystallography on proteins – Dorothy Crowfoot Hodgkin

Proteins have a lot of atoms, and It took a while to get to being able to solve the structures of such large molecules – Dorothy’s early work was on “simpler” molecules, work which was nonetheless crucial. After solving the structure of the antibiotic penicillin in 1945 with Barbara Low (more below), she kept honing the techniques, enabling her to figure out the structure of the most complex vitamin (vitamin B12) in 1955, and – her lifelong goal – the protein hormone insulin in 1969. She won the Nobel Prize in Chemistry in 1964 – the 3rd woman to do so. 

In addition to an incredible scientist, Hodgkin was active in opposing nuclear weapons and she advocated for women in science everywhere; she worked at a time when women lost fellowships and research grants when they married, with their funders claiming the women were now “living at home” with their spouses providing for them. Dorothy spoke out against these ludicrous policies, portioning for individual affected women when the issue arose time and time again. She also directly mentored several female scientists who went on to become influential crystallographers in their own right. 

One of those was Barbara Low, who was a graduate student at the time she helped determine the structure of the antibiotic penicillin. Its discovery came at a time it was greatly needed. It was in the midst of World War II, when battlefield wounds and infections were rampant, and knowing the structure helped chemists develop modified versions of penicillin to treat a wider range of infections.

Barbara Low went on to become a big-wig crystallographer in her own right, discovering among many things, the “pi helix” – a special type of shape (conformation) that parts of proteins often form (for the geeky among us, this is where N-H groups in the protein backbone hydrogen-bond with C=O groups 5 letters upstream (instead of the “usual” 4 you find in the more common alpha helix). She also carried out early work on the structure of insulin & neurotoxins like those found in snake venoms – and her findings helped scientists better understand how brain receptors for a signaling molecule called acetylcholine work.

While we’re on the topic of disease-stopping, let’s switch tracks from bacteria to viruses and talk about HIV and the Nucleoside Analogue Reverse Transcriptase Inhibitor (NRTI) AZT. Do you know about Janet Litster Rideout? She was one of the scientists who discovered that the DNA-letter mimic AZT (azidothymidine aka zidovudine aka Retrovir) could be used to treat the AIDS-causing HIV virus. quick note: if some of this looks like it was copied and pasted from Wikipedia, it was, but that’s cuz I wrote the Wikipedia article – and I hope you all will take it upon yourself to write/edit articles too!

HIV is a retrovirus, a type of virus that transfers between cells with its genome encoded in RNA but, once it infects a host cell, reverse transcribes its RNA genome into a DNA copy which it then inserts into the host cell’s DNA, so that the cell and all its progeny are perpetually infected. AZT mimics the DNA letter T, but doesn’t have the part needed to link to the next letter. So, when the HIV virus goes to reverse transcribe its RNA to make a DNA copy that it can integrate into the host cell’s DNA, it adds the fake letter and gets stuck, so it can’t integrate. AZT was the 1st HIV treatment & remains an important component in the fight against HIV/AIDS (along with things like protease inhibitors which prevent the virus from making functional protein). Rideout also played a key role in the development of acyclovir, the first effective treatment for herpes simplex virus

Combining both bacteria and viruses was the work of Martha Chase. While working as an assistant to Alfred Hershey at Cold Spring Harbor Laboratory, she carried out the famous “Hershey-Chase” experiments (aka Waring Blender experiments) that helped show that DNA and not proteins holds and transmits genetic information. They took a virus that infects bacteria (a bacteriophage or “phage”) and radioactively-labeled its DNA or its protein and then let it infect bacteria. During the infection process, the phage docks onto the bacteria surface and injects its DNA, while the outer capsule that was carrying it, made up of protein, remains on the surface. So DNA goes in, protein stays out, and, when they used a blender to shear off the stuck-to-the-surface protein capsules, they found that radioactivity would only be inside the bacteria when they labeled the DNA, not the protein. This experiment helped win Hershey the Nobel Prize – and he didn’t even mention Martha in his speech.

Another notable Nobel-less name is Rosalind Franklin. She (well, her graduate student Raymond Gossling) took the famous “Photo 51” fiber diffraction image of DNA – that “blurry X” which was shared without her permission while she was working out her interpretation of it – which Watson and Crick used to make their model of the DNA double helix (DNA hangs out as 2 strands antiparallel to one another with the bases facing in, phosphates on the out). 

That DNA stuff was only a brief stint in an incredibly productive, though tragically short, career. Before it, she performed research on coal and carbon that made possible carbon fiber technologies and after it, she made key insights into the structure of viruses including polio and tobacco mosaic virus (TMV). And a fun fact I learned is that she created giant 3D models for the 1958 Brussels World’s Fair). Franklin would have undoubtedly made more discoveries were her life not cut tragically short by ovarian cancer. She passed away in 1959 at the age of 37 and Watson, Crick, & Wilkins got the Nobel Prize in 1962 for the DNA structure discovery she played a key role in.

Looking at “structure” at a larger level was Eileen Southgate who mapped out the layout of the nervous system of a very tiny rooundworm – C. elegans. Working as a laboratory technician, she, along with John White and Nichol Thomson in the 1980s, under the guidance of Sydney Brenner, mapped (by hand from ~8,000 serial section electron micrograph prints) every single nerve cell in the worm Caenorhabditis elegans (C. elegans). This was the first time such a map of an animal’s “mind” had been made, and it has helped scientists study and understand nervous system development and functioning. 

A lot of the nerves she traced connected to muscles, allowing the nervous system to tell muscles to move. But how do muscles manage that movement? This brings us to the work of Ilona Banga, a Hungarian biochemist who codiscovered (along with Albert Szent-Györgyi & Bruno Straub) actomyosin – the actin/myosin combo that makes muscles contract so you can act! She made that co-discovery while working as a research assistant in the lab of Albert Szent-Györgyi at the University of Szeged. Before the muscle stuff, she contributed to the work that earned Szent-Györgyi the Nobel Prize in 1937. The prize was for work they did on metabolism and vitamin C. And to do that work they needed a lot of it. So she developed methods for purifying large amounts of ascorbic acid (vitamin C) from Hungarian paprika –  and a ton of it – literally (at least almost literally) – the protocol involves 450 liters of paprika pulp! All that gave her 3kg of the stuff – which you can now buy online for less than $60.

When Szent-Györgyi set his sights on muscles, Banga jumped right in. Something that makes Banga and her co-workers’ discoveries all the more remarkable were that they were being carried out in occupied Hungary during WWII. Szent-Györgyi had to go into hiding because he was wanted because of his anti-Nazi activities. This left Banga to protect the lab and all of its valuable research equipment – and that was no small task. Towards the end of the war, German troops were leaving, Soviet troops were arriving, and Hungarian thieves were always present. So she posted notes (written in German, Russian, and Hungarian) on the door of the Institute of Chemistry saying it was researching infectious things and providing sample drop-off hours for infectious materials. This scared away anyone who wanted to take their equipment and the Institute for Medicinal Chemistry remained intact – it was the only institute at the university to not have its facilities or equipment damaged. 

When Szent-György left Hungary for the US after the war, Banga stayed. And took a new position –  chief of the Chemical Laboratory of the First Institute of Pathological Anatomy in Budapest, and a new research partner – the pathologust József Baló, whom she married and  worked closely with until his death in 1979. Much of their work focused on changes that occur to your veins when you age. They were interested in figuring out what causes degradation of the elastin fibers holding together the walls of veins – and their searching efforts proved not to be in vain! They found an enzyme made by the pancreas that could do it – so they named it elastase. Turns out there are actually more elastases and this one probably doesn’t play a role in arteriosclerosis but it was the first one discovered – and Banga and Balo did it! Fellow scientists were skeptical but Banga was able to crystallize elastase (and her conclusion)!

Another woman who did work with her husband was Sylvey Kornberg. She’s often overshadowed by her husband. Nobel laureate Arthur Kornberg, as well as her son, Roger, who also won a Nobel, but Sylvey was an important biochemist in her own right. She made findings that made Arthur’s findings about DNA copying possible – they were trying to study DNA copying (replication) “in vitro” (outside of cells) using DNA letters and DNA polymerase (the letter-linker), but they’d hit a roadblock. Sylvey helped “unblock” the work by discovering and characterizing an enzyme that was degrading the DNA letter G.

She also discovered an enzyme that could make long chains of phosphate (polyphosphate, or PolyP). It turns out a lot of microorganisms make PolyP chains hundreds of phosphates long, and scientists are still trying to figure out exactly why – it probably has multiple functions including helping to regulate gene expression, storing metal cations like iron (Fe2+) (PolyP’s negativity makes it well-suited for this), and acting as an energy source (lots of high-energy bonds). Humans use polyP too, but not such long ones – instead, we have shorter, 60-100 phosphate-long chains that are stored in our blood platelets and released to help out with blood clotting. Her discovery of polyphosphate kinase was only the second type of enzymatic polymerization (molecule-link-upping) ever discovered.

And last, but definitely not least, I want to give a huge shoutout to Maud Menten, whose last name might sound familiar to you for a different reason than Kornberg –  if you’ve ever taken a biochemistry course (and/or if you’ve read my post on enzyme kinetics), you’ll recognize it as being half the name of the “Michaelis-Menten equation” for enzyme kinetics. Enzymes (often proteins, sometimes protein/RNA, sometimes just RNA) are biological catalysts – they mediate and speed up biochemical reactions. Their jobs range from breaking things (e.g. restriction enzymes cutting DNA) to making things (e.g. DNA polymerase copying DNA) and how fast they can do it (convert the starting materials (substrate) to the final product) depends on things like how much they like the substrate (reflected in Km) and how good they are at changing it (reflected in kcat).

In the early 1900s, Maud Menten & Leonor Michaelis figured out a mathematical formula that connects these various fundamental properties of an enzyme to observable things (like the disappearance of reactants and/or appearance of products over time). This allows scientists to do enzyme activity experiments to do things like see which substrates an enzyme prefers and which enzymes are most efficient under different conditions. 

Dorothy Crowfoot Hodgkin:  http://bit.ly/dorothycrowfoothodgkin 

Barbara Low: http://bit.ly/penamp

Janet Lister Rideout: http://bit.ly/38yNyib

Martha Chase: http://bit.ly/hersheychaseexp 

Rosalind Franklin: http://bit.ly/rosalindfranklincoal

Eileen Southgate:  http://bit.ly/eileensouthgate

Ilona Banga:  http://bit.ly/ilonabanga

Sylvey Kornberg: http://bit.ly/sylvy_kornberg

Maud Menten:  http://bit.ly/mentenkinetics

more on topics mentioned (& others) #365DaysOfScience All (with topics listed) 👉 http://bit.ly/2OllAB0

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