The Unsung Heroines of Science

In a time we celebrate women and their incredible achievements in every field there is, I feel we should take some time to celebrate the women who have made startling discoveries but have gone without recognition. These unsung heroines teach us lessons which no success story can teach. These are women, who made history; changed the course of research; gave life to new fields of study in Medicine; were victims of the Matilda effect.

 “It is sometimes better to be a dead man than to live a woman.”

— wrote Matilda Joslyn Gage, on laws which allowed a man to will his children to a guardian unrelated to their mother.

 The Matilda effect was experienced and articulated by her, which refers to the common bias by which the achievements and great discoveries by women scientists are ignored, denied credit, or otherwise dropped from sight, simply because they are by women!

This caused many male scientists to take credit (and awards like the Nobel Prize) for ground-breaking accomplishments that were actually by the women scientists.

 Some Victims of the Matilda Effect:

Rosalind Franklin:

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British Scientist Rosalind Franklin at work on the microscope

“You look at science (or at least talk of it) as some sort of demoralizing invention of man, something apart from real life, and which must be cautiously guarded and kept separate from everyday existence. But science and everyday life cannot and should not be separated.”

-Rosalind Franklin

(Letter to her father, Ellis Franklin. Excerpted in Brenda Maddox, The Dark Lady of DNA)

Talk about the discovery of the structure of the DNA – the fundamental hereditary material in every cell of a living organism – and the names Watson and Crick come to mind. That’s what our textbooks taught us. The discovery is attributed to them more because of their winning of the Nobel Prize for the same. But the person who must have been rightfully credited for the discovery is a woman.

Born on July 25, 1920, in London as Rosalind Elsie Franklin, she was the second of five children in a prominent Anglo – Jewish family.  She chose Science as her subject at the age of sixteen, despite her father wanting her to do social work. She majored in Physical Chemistry at Cambridge University, and received her BA, a scholarship for an extended year in research, and a research grant from the Department of Scientific and Industrial Research in 1941. With World War II still on, she chose to pursue a Ph.D. oriented research job in a field relevant to wartime needs.

She worked with the British Coal Utilization Research Association (BCURA) for four years to elucidate the micro-structures of various coals and carbon. She found that the pores in coal have fine constrictions at a molecular level which act as ‘molecular sieves’ successively blocking penetration of substances. In this original work, Franklin was the first to study, identify, and measure micro-structures, resulting in the classification of coals and prediction of their performance to high levels of accuracy. The production and use of gas masks by British soldiers which used carbon to protect from the various poisonous gases was based on Franklin’s research. She received her Ph.D. and published five scientific papers from Cambridge in 1945.

Adrienne Weill, her mentor and friend, helped Franklin get a position in Jacques Mering’s Lab at the Laboratoire Central des Services Chimique de l’Etat in Paris, after the war. She learned how to analyze carbons using x-ray crystallography and became very proficient with the technique.

On a friend’s suggestion she took to doing x-ray diffractions studies on large biological molecules. With a three-year Turner and Newall Fellowship she moved to King’s College, London to work in John T. Randall’s Biophysics unit. Maurice Wilkins, the assistant lab chief, suggested Randall to ask Franklin to investigate DNA instead of proteins. Randall did so, but failed to communicate to Franklin that she was supposed to work together with Wilkins. Franklin, along with a graduate student, Raymond Gosling, began their analysis on DNA. Franklin and Wilkins suffered many misunderstandings, as Franklin assumed he interfered with her work.

Being an outspoken and bold woman, Franklin never feared to voice out her opinion which intimidated Wilkins and her many other male colleagues. Female researchers were expected to work as ‘assistants’ or ‘subordinates’ to male researchers. Women were discouraged from doing independent research. But Franklin remained undeterred and continued on her research despite the many difficulties she faced; she had to leave the building for lunch everyday as women were not allowed in the College Cafeteria; she was called ‘Dark Lady’, because she disliked being there and was very unhappy.

Despite all of this she kept going on. Franklin and Gosling progressed in their research and took increasingly clear x-ray diffraction photos of DNA. They could see two forms of DNA. One was called the dry or ‘A’ form, the other wet or ‘B’ form. Each X-ray chromatograph had to be exposed for over 100 hours to form an image, and the drier ‘A’ form seemed likelier to produce images in more detail. Franklin decided to work on that. She noticed that the ‘B’ form image showed a definite helical structure with two strands clearly visible. She labeled it ‘Photo 51’ and filed it away. By 1953, she concluded that both forms had two helices.

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Photo 51

During this time, Watson and Crick, who were friends of Wilkins, were working on modeling the DNA structure at the Cavendish Laboratory at Cambridge. During a conference, they presented their theoretical model. Franklin, who was present, was critical of their work because it was based solely on conjecture, unlike hers which was based on solid evidence. This criticism widened the gap between her and Wilkins.

Later on, unknown to Franklin, Wilkins came in possession of her notes and ‘Photo 51’. He removed the photograph along with a summary of her unpublished paper and showed them to Watson and Crick, without her consent. Being enlightened with such precise evidence, Watson and Crick built their ‘double helix’ model and published their work in Nature.

Oblivious to all these events, Franklin halted her work at King’s and decided to transfer her fellowship to J. D. Bernal’s crystallography laboratory at Birkbeck College. She worked on plant viruses and pursued to make important discoveries about virus structures.

In the fall of 1956, Franklin was diagnosed with ovarian cancer, possibly caused due to the exposure to radiations from working on x-ray diffraction instruments. She underwent many surgeries, yet continued to work in her lab. She died in London on April 16, 1958.

Had she lived to continue her work, she would have received awards and professional recognition for her ground breaking work on viruses.

In 1962, Watson, Crick, and Wilkins received the Nobel Prize in Medicine for work on DNA structure. The Nobel Prize is not awarded posthumous and it could only be shared by 3 scientists. Even if Franklin was alive in 1962, her research would have only been a footnote in Watson and Crick’s paper. She was denied recognition and praise for her work only because she was a woman.

In Watson’s 1968 memoir, The Double helix, he portrayed Franklin as ‘Rosy’ (the name which Franklin disliked being called the most), a bad tempered, arrogant bluestocking who jealously guarded her data from colleagues, even though she was not competent to interpret it. The book was criticized immensely for its sexist views and belittlement of the works of a wonderful female researcher, Rosalind Franklin. Franklin’s friend Anne Sayre published a biography in angry rebuttal to Watson’s account, called Rosalind Franklin and DNA. The biography gave an insight into Franklin’s life and research and told the world the real story. She was cheated of a Nobel Prize by both misogynist colleagues and by an early death. In the past decade people have begun to recognize her works and appreciate them. Currently many honors are given to women researchers in her name and the Rosalind Franklin University of Medicine and Science was founded. But we all know now that she died without the honor and recognition she rightfully deserved.

Esther Lederberg:

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Esther Lederberg during a lecture

Back then, till 1950, it was believed that a bacterial virus or bacteriophage underwent a ‘lytic’ cycle of reproduction – a single viral DNA enters into bacterial cell and it remains a free floating separate molecule to the host DNA, it multiplies in number causing lysis or death of the host; and the multiple viral DNA leave to infect other cells – but in 1951 another type of viral reproduction was discovered in a newly isolated bacteriophage, and it was done by a woman.

On December 18th, 1922, Esther Miriam Zimmer, the first of two children was born to David Zimmer and Pauline Geller Zimmer. A child of the Great Depression, her lunch was often a piece of bread topped by the juice of a squeezed tomato. She attended Evander Childs High School in Bronx, and graduated at the age of 16 with honors in French. When she was a kid, she willed her grandfather to teach her Hebrew. It seems normal to us, but then it was an unusual request because in Orthodox families girls weren’t taught Hebrew. Her grandfather was happy to see her interest and taught her. She learnt Hebrew faster than her cousins and did all the Hebrew reading for the Passover Seders.

She was asked to do work that was offered to women during the war times but she refused, knowing that those jobs will not last. Zimmer had a passion for science, especially genetics. She worked at the New York Botanical Garden, engaging in research on Neurospora crassa. She graduated cum laude at the age of 20.

Zimmer continued to work on Neurospora and published her first work in genetics. She won a fellowship to Stanford University. She did masters program in genetics and worked on bacterial genetics.

On December 13, 1946 she married Joshua Lederberg to become Esther Lederberg. She began work at the University of Wisconsin with her husband.

Esther Lederberg was the first to isolate λ bacteriophage. She observed colonies of mixed culture of Escherichia Coli K-12 and a strain that had been irradiated with ultraviolet light called W-518. It was believed that the lambda was located in the cytoplasm, but Lederberg found out that that wasn’t the case. Her data suggested that the lambda should be located on the chromosome, at a specific locus for ‘lysogeny’.

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Lambda Phage

This resulted in Lederberg discovering the ‘Lysogenic’ cycle of viral reproduction, where the viral DNA exists as a part of the DNA of the host and not as a separate molecule. The host does not recognize the viral DNA, and assumes it to be its own. The viral DNA also remains dormant. When the bacterium reproduces, its daughter cells also contain the viral DNA. The host cells remain unharmed but when exposed to UV radiation or when deprived of nutrients, the viral DNA activates and undergoes the ‘lytic’ cycle as explained earlier. Unlike other viruses that multiply rapidly inside a host cell and kill it, the lambda phage integrates its DNA into that of the infected bacteria. This allows the virus to pass on its genetic instructions to produce progeny viruses to new generations of bacteria without destroying the host organism. She established further that the process was helped by a mediator she called ‘Bacterial Fertility Factor F’.

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This discovery is a major breakthrough. The same cycles are said to occur with Herpes virus and many other deadly viruses that go undetected in humans and other eukaryotes. The Lambda phage found its application as a vector for cloning of recombinant DNA and many other methods in DNA engineering. It is a key tool in molecular biology because it can easily be grown in E-coli and is not pathogenic except in the case of bacteria. It has proven particularly helpful in understanding the transfer of genetic material between bacteria, the mechanisms involved in gene regulation and how pieces of DNA break apart and recombine to make new genes

Lederberg continued to research and went on to invent Replica Plating. This method enables scientists to replicate bacteria colonies on a series of agar plates with exactly the same spatial configuration. Having access to replica bacteria colonies was important for comparing bacterial reactions to environmental changes such as nutrition or temperature.

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Replica Plating

Each of her discoveries was her individual work with comments and suggestions from her husband and colleagues. But it was Joshua Lederberg who received the Nobel Prize in 1958 with two others which did not include Esther Lederberg. Esther Lederberg was responsible for most of the discoveries but since her husband was also a researcher, all her works’ credits went to him. She lived in the shadow of her husband making the most remarkable discoveries which were crucial for Joshua Lederberg’s research. In all of her papers except the one on Lambda phage, her husband and colleagues were mentioned as co-authors and they received credit. Joshua Lederberg, during his speech at the Nobel Prize ceremony and the gala dinner, failed to mention Esther’s contributions to his research.

Beyond Science Esther Lederberg had cultural interests. She was a devotee of Early Music. She was one of the founding members of the Mid – Peninsula Recorder Orchestra and served as president for several years. She also had an eclectic taste in literature.

She received a few honors and was the President of the Stanford Chapter of Sigma Xi. She divorced Joshua Lederberg in 1966 and married Matthew Simon in 1993. Esther Lederberg died of pneumonia and congestive heart failure on November 11, 2006 at the age of 83.

“She [Esther Lederberg] did pioneering work in genetics, but it was her husband who won a Noble price.” said an obituary in the British newspaper The Guardian. “She [Esther Lederberg] had to fight just to be appointed as a researched associate professor, where she surely should have been afforded full professorial rank. She was not alone. Women were treated badly in academia in those days.” Spoke Stanley Falkow, a retired microbiologist at Stanford University during Lederberg’s memorial service.

As far as I’ve searched the internet, there is not one page that is officially dedicated to her, or in the Profiles of Science of the U.S. National Library of medicine website in Esther Lederberg’s name. There’s one page in Joshua Lederberg’s name, which has not a single word of mention about Esther Lederberg.

Martha Chase:

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Dr. Martha Chase and Dr. Alfred Hershey

Most of us would’ve read about the “Hershey – Chase” experiment or simply the “the blender experiment” in our biology text books. It is a simple but very important experiment that showed that the genes were made up of the DNA and not proteins. Till then, scientists were the least bothered about DNA, not knowing that it indeed was the inheritable genetic material. Most of us wouldn’t have realized that Chase was a woman.

            Martha Cowels Chase was born on November 30, 1927 in Cleveland Heights, Ohio. Her father was a medical school professor at Case Western Reserve University. She grew up with science, received her bachelor’s degree from the college of Wooster in 1950. During her undergrad days she did her first genetic experiments on fruit flies.

           Chase began her work as a research technician in the lab of Dr. Alfred Hershey at Cold Spring Harbor Laboratory on Long Island when she was 21. She was part of the ‘Phage group’ which included researchers Salvador Luria, Max Delbruck and Alfred Hershey. They researched bacteriophages which infected bacteria to find out what the genetic material of the phage could be. The bacteriophage has a head which contains DNA and a tail which contains protein. It was strongly believed then that the protein in the tail was the genetic material that was inherited by the following generations, but the theory could not be proved. ‘The Phage group’ was focused on finding the answer.

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Bacteriophages infecting a bacterial cell

In 1952, Hershey and Chase conducted the famous ‘blender experiment’. Hershey strongly believed that the genetic material was protein and wanted to disprove the idea of DNA and hence, with Chase he conducted the experiment.

While the structure of the DNA wasn’t known then, it was known that the DNA contained phosphorus (P) atoms but no sulfur (S) atoms. Contrary to this, a protein contained sulfur but no phosphorus (except in the case when under certain conditions, the enzyme kinase adds phosphate groups to proteins). With this fact and that the protein and DNA have different chemical compositions; they took DNA phages (labeled with P-32, a radio isotope of phosphorous) and infected more E.coli bacteria. They then put the mix into a Warring Blender to sheer-off the parts of the phages that remained stuck on the outside of the bacteria carefully so as not to disrupt the bacteria themselves. After blending, Hershey and Chase separated the bacteria and phage in a centrifuge. A centrifuge spins at high speed with a test tube containing the sample in order to separate the contents based on a size and density (blood samples are tested using a centrifuge). The bigger and heavier cells sank to the bottom of the test tube while the lighter ones remained on the top.

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While they looked at how much radioactive phage material was transferred to the bacteria they found out that the radioactive DNA with P-32 was seen inside the bacterial cells but the radioactive protein with S-35 wasn’t present anywhere in the bacterial cell. These results showed that during infection, the phages were transmitting their DNA, and not their protein, to the bacterial cells. Thus, Hershey and Chase concluded that that DNA is the hereditary material. This contradicted Hershey’s belief which he went on to accept due to the strong experimental data they had. The Hershey and Chase experimental results played a key role in Watson and Crick’s modeling of the DNA which they completed 11 months after the ‘blender experiment’.

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The famous Warring Blender

This experiment marked the pinnacle of Chase’s scientific career but it didn’t make her life easier. In 1953, she left Cold Spring Harbor, and went to the University of Southern California to perform her PhD, which she received in 1964. After that her scientific career saw a downfall. She never gained the credit for her work at Cold Spring Harbor or other places outside. Chase was laid off from her research job at USC. That and a combination of illness made her to move to Cleveland to live with her father, Samuel Chase. In late 1950s, Chase married Richard Epstein, a fellow scientist she had met in California. But they divorced within a year and it left a deep scar.

            In 1969, she witnessed Alfred Hershey and the 2 other male colleagues receive the Nobel Prize, for their contributions to the ‘genetic structure of the viruses.’ She was sidelined by the Nobel committee as merely ‘technical assistance’ for the men who ran the show. Though her name being put on the paper published in the Journal of General Physiology by Hershey, in itself suggests that her role in the discovery was more than mere ‘technical assistance’, Hershey himself provided the biggest insult to Martha Chase by never even mentioning her name or her role during his Noble lecture, titled “Idiosyncrasies of DNA Structure”.

This event of disgrace, her divorce, and the difficulties she faced in her scientific career led her to drink heavily and smoke. It led to her many health problems. Martha Chase suffered from dementia for decades and died of pneumonia on August 8th, 2003. The New York Times obituary for Martha Chase reads, “Martha Chase, 75, Researcher Who Aided in DNA Experiment.” She was often called as a ‘remarkable but tragic person’; but we all know that her tragedy is attributed to the people who surrounded her life rather than her inability to live through the pain. In fact she was an adventurer who, “.. Especially loved going out in the desert after a rain when the flowers were blooming”. Chase enjoyed knitting, sewing and photography.

“The harder the pattern the better she liked it….She was always interested in anything that was a challenge.” said Martha Chase’s Sister Ruth Daziel.

In December 1903, Marie Curie was the first woman to ever be awarded the Nobel Prize.

Makes us happier after reading all the tragic stories, right? There’s an incident behind it too. Like always the Nobel Committee intended to honor only Pierre Curie and Henri Becquerel with the Nobel Prize in Physics, but one of the committee members, an advocate of women scientists, alerted Pierre to this and he filed a complaint. Upon accepting the complaint, Marie’s name was added to the nomination and then she was awarded the Nobel Prize. If like the other men mentioned above, Pierre had decided to ignore Marie then she wouldn’t have ever shared the Prize with him. Marie wasn’t even allowed to give a speech at the Nobel Prize ceremony because she was a woman.

Imagine the pain each of these women and the many more unaccounted had to go through even though they did revolutionizing discoveries with their brilliant minds, in science. They were the reasons new fields of research and study emerged in science. Being a woman was their only crime. Their voices were silenced and they were pushed to the background as ‘assistants’, ‘a set of hands’ which helped while the other men did the important work. They were supposed to be honored and held in high positions when they were alive. Though we realize the injustice done to them, we can only feel proud that they accomplished so much, and guilty that there wasn’t a person in their life to uplift them. In each of the stories, except in the case of Marie Curie, the men in their lives shamelessly took their works and called them their own. The men smiled in the spotlight without a hint of guilt even though they have stolen the hard work of the women who were behind their success. Such was the height of chauvinism at that time. But like we always do, women then kept going on. They kept moving forward ignoring the negatives and doing what they do best for a selfless cause. We can do nothing for them now, but take inspiration from them to remain undeterred and help women gain recognition and applause for all of their achievements; make the Matilda effect non – existent. A world with equal recognition for men and women can be achieved not only by women who stand up for their and every other women’s rights, but also with the help of men who are ready to support and treat women as their equals. The prosperity of a society and humanity as a whole lies in the willingness of men and women to accept and respect each other; to work together without dominance or discrimination.

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