An Interview with Manuel F. Varela and Ann F. Varela: Dr. Marie Daly and Cholesterol, Histones, Hypertension, Atherosclerosis, and Smoking

Sep 18, 2021 by

Dr. Marie Daly

Courage to be is the key to revelatory power of the feminist revolution.”

––Marie Maynard Daly

If I must return to teaching, I would not mind if I could have the opportunity and facilities for continuous research.”

––Marie Maynard Daly

Courage is a habit, a virtue: you get it by courageous acts. It’s like you learn to swim by swimming. You learn courage by couraging.”

––Maynard Maynard Daly

Michael F. Shaughnessy

1) Some people contribute mightily to science—but do not necessarily win the Nobel Prize—Marie Maynard Daly studied the chemistry of histones, the realm of protein synthesis, the link between cholesterol and hypertension, and lastly, creatine—and its uptake by various muscle cells—I get tired just reading about all the work she did—When and where was she born and where did she go to school?

Marie Maynard Daly is well known amongst historians of science for her groundbreaking research on histones, protein translation, cholesterol, atherosclerosis, hypertension, smoking, and creatine biochemistry. Daly was born in the Corona borough of Queens, New York, New York, on April 16, 1921. Her parents were passionate about the value of a good education. Her father, Ivan C. Daly, emigrated from the West Indies as a young man and attended Cornell University to pursue a chemistry degree. Unfortunately, his dream was cut short by a lack of funds to complete his course requirements. Thus, he returned to New York and became a clerk for the United States Postal Service. Daly’s mother, Helen, was raised in Washington, D.C., and was an avid reader. She passed along this trait to her daughters by reading aloud from books mainly about science and scientists. The one book that Daly found particularly fascinating was Paul De Kruif’s well-liked book The Microbe Hunters.

Daly attended an all-girls school in New York City called Hunter College High School. The faculty there fortified and championed her interests in chemistry. She then attended Queens College in Flushing, New York, and lived at home to save money. In 1942, she graduated with magna cum laude honors and was named a Queens College Scholar, which only is granted to the top 2.5% of the graduating class. In 1961, Daly married Vincent Clark.

2) It probably should be noted that she was the first African American to get a chemistry doctorate from Columbia University in New York City. When did this occur? Moreover, what were some surrounding issues?

Significant historical events shaped the life and experiences of Daly. She was a youth during the Great Depression and a young adult during WWII, the integration of schools, voting privileges, and the Civil Rights Act.

Continuing her education required funding. Money was tight, but Daly was fortunate enough to work as a lab assistant at Queens College and simultaneously obtained a fellowship at New York University to pursue her master’s and Ph.D. degrees in chemistry. Daly was both determined and clever. She also took full advantage of what was going on in history. World War II was at its peak, and employers sought women to fill the void left behind by men joining the military and shipping off to fight overseas. The timing was definitely on her side as Daly took her graduate degree in chemistry one year later in 1943 and then enrolled in the doctoral program at Columbia University.

Mary Letitia Caldwell, whose specialty was nutrition, supervised Daly. Their focus was concentrated on how chemicals produced in the body contribute to food digestion. Daly’s thesis centered on “A Study of the Products Formed By the Action of Pancreatic Amylase on Corn Starch.” In 1947, Daly took her Ph.D. in chemistry, becoming the first African American to receive a Ph.D. from Columbia University and the first African American woman to receive a chemistry Ph.D. in the United States.

3) Histones—what are they are? Why are they important?

Histones are proteins that are associated with DNA and are found in the nuclei of living cells. The histone proteins are foundations upon which DNA coils, forming macromolecular structures called nucleosomes. See Figure 1. Furthermore, histones can be thought of as DNA-binding proteins, and their cellular function is to help stabilize genomic and chromosomal DNA to pack efficiently inside the nucleus of the intact cell. The binding of histones to DNA is independent of the nucleotide sequences, unlike many other proteins, which require specific sequences for proper binding to DNA. Eukaryotic and archaeal bacteria, but not prokaryotes, it seems, have histones.

Histones stabilize and pack genomic DNA strands in the cell nucleus, forming nucleosomes connected by linker DNA. During the cell’s chromosome packing, the nucleosomes aggregate to make larger structures called chromatin fibers. In general, there are two types of these fibers. Chromatin that is “active” is called euchromatin, while the inactive fiber forms are called heterochromatin. When a cell undergoes multiplication by mitosis to produce two daughter cells, the chromatin is completely replicated to make two copies of the chromosome. During this duplicative process, the newly synthesized chromatin molecules condense into configurations that can be seen on a microscope.

Figure 1. Schematic representation of a histone bound to DNA to make a nucleosome, the smallest subunit of the chromatin.

File:Complete Histone with DNA.png

While at the Rockefeller Institute, working as a postdoctoral fellow under Alfred E. Mirsky, Dr. Daly pursued an interest in the internal workings of the cell’s nucleus. Daly studied the molecular composition and biochemistry of nuclear protein. At the time, two main types of nuclear protein were known, the protamines and the histones. These two types of proteins were thought to differ in their constitution of amino acids.

In the laboratory, Daly prepared histone material from the blood and sperm of roosters and the livers and thymuses of calves while in a so-called cold room, which was set at two degrees centigrade (°C), about 36 degrees Fahrenheit. Likewise, Daly prepared protamines from rooster sperm, referred to as the sperm of fowl in their 1950 scientific article. The nuclear protein isolation work was painstaking and arduous. Daly worked with various incubation temperatures, plus concentrated acids and alkali. During each of the successive chemical steps in the isolation protocol, she had to ensure the presence of protein with spectrophotometric analyses, confirming that each step was correctly done as indicated by high protein concentration measurements. Furthermore, Daly had to ensure that no confounding nucleic acid material was present in the nuclear protein preparations. Once the histones and protamines preparations were completed, Daly could commence with determining their amino acid composition.

The amino acid analyses for the composition of the cell nuclei protein were just as labor-intensive as the previous set of lab methods used to prepare protein. The histones and protamines first had to be broken up into pieces by conducting a hydrolyzing reflux procedure at least 200 times while using highly concentrated hydrochloric acid for 18 hours straight. Next, Daly used starch chromatographic columns to separate the individual amino acids in the nuclear protein hydrolysates. Next, she analyzed the relative concentrations of the individual amino acids using a spectrophotometer to visualize the heights of various peaks corresponding to their specific amounts.

Daly found that the histones seemed to reside primarily within the somatic cell chromosomes while the protamines were in the sperm nuclei, noting that significant variations were found in the amino acid compositions in the proteins of both types of nuclei. Interestingly, Daly and her colleagues, Mirsky and Hans Ris, coined the term “gallin” to denote the specific protamines they found in the sperm of the Gallic rooster of the Gallus genus. Daly, Mirsky, and Ris would publish together in the Journal of General Physiology in 1950, with Daly as the first author.Importantly, this early work by Daly would later form the basis of our modern biochemistry knowledge about the nature and function of histones.

Besides studying the nuclear amino acid composition and histones, Daly’s work included an analysis of so-called ribonucleoproteins. These complexes of RNA and protein were involved in the protein-making process of translation inside the pancreas and liver cells of laboratory mice.

In the pancreas, Daly prepared sub-cellular structures called microsomes, later known as ribosomes, involved in protein synthesis. These intracellular structures harbored a ribonucleoprotein component, which was studied closely. Daly found that the individual protein and RNA pieces of the microsomes participated in the uptake of the radioactively labeled amino acid glycine. The investigators noticed a correlation between the levels of RNA and the amount of protein synthesized. The levels of the RNA-protein complexes seemed to also correlate with the incorporation of radioactive incorporation of glycine into the newly made protein. In the pancreas, Daly and colleagues noted the presence of two protein groups. One group of proteins seemed to be destined for secretion to the outside of the pancreatic cells. The other set of proteins appeared to be associated with the protein-making machinery of the cell. These data dealing with cellular translation and the functional role of ribonucleoprotein in the pancreas was published in November of 1953 in the Journal of General Physiology. The published work would generate the attention of Nobel Laureates, one of whom would cite Daly’s work in their banquet address.

In the liver studies, Daly and her colleagues prepared the diets of laboratory mice who were either not previously fed for several days or were provided a high glucose diet for a week. The laboratory mice were then injected with glycine, which was radioactively labeled with nitrogen-15. The mice livers were then tested for total protein levels and measurements of radioactivity to examine the rates of nitrogen incorporation into protein and RNA. The new findings showed that liver cells effectively used glycine to produce so-called nucleoprotein molecules. Daly published the work in the Journal of Histochemistry & Cytochemistry in September of 1954.

Dr. Daly was also involved in analyzing the purine and pyrimidine content of DNA in the cell’s nucleus. Interestingly, her studies were performed when DNA was not considered of prime significance as genetic material. Thus, her analysis of nuclear nucleic acids can be regarded as far ahead of her time.

4) Purines and pyrimidines in desoxypentose nucleic acids seemed to be a central aspect of her work. Why is this realm essential, and what did she find?

In modern times, the word desoxypentose of the early 20th century refers to 2-deoxyribose sugar. The term desoxypentose nucleic acids is commonly known today as deoxyribonucleic acid (DNA). Today we know that DNA is famous because it harbors the coded instructions for conferring life’s structure and functions. Marie Daly studied the purine and pyrimidine nitrogenous bases of DNA in the early 1950s.

While the significance of DNA was not widely appreciated in Daly’s day, in the late 1940s, the molecule was indeed studied intensively by her before it became famous amongst the molecular biologists and biochemists of the day. In Mirsky’s laboratory, Daly first devised a chromatographic column technique for separating the purines and pyrimidines, publishing the method in a short paper in the Journal of Biological Chemistry in 1949. See Figure 2. Next, Daly, Mirsky, and V.G. Allfrey set out to address several questions using their new method.

File:Purine and Pyrimidine.png

Figure 2. Purine and pyrimidine molecules.

First, Daly and colleagues were curious whether DNA harbored nitrogenous bases other than the previously known adenine, cytosine, thymine, and guanine, such as, for instance, hypoxanthine or uracil. Astutely, Daly found that after preparing DNA from the blood, organs, and tissues of a variety of living organisms, such as young cows, horses, chickens, turtles, fish, sea urchins, and bacteria, their DNA samples harbored only four nucleotides. We know these bases to be adenosine (A), guanine (G), cytosine (C), and thymine (T). Daly had been correct about her assessment of the nitrogenous base content of DNA in 1949 when it had before been unclear.

Second, Daly addressed the so-called tetranucleotide hypothesis. First proposed in the early 1900s by Phoebus Aaron Levene, Herman Steudel, L.W. Bass, J.A. Mandel, and others, the tetranucleotide hypothesis stated that the four nitrogenous bases were present in DNA in equal concentrations in the cells of living organisms. The tetranucleotide hypothesis was a controversial issue, as not everyone interested in DNA agreed with the idea. Others like J.M. Gulland and Erwin Chargaff had observed different ratios of the four bases in many distinctive organisms. However, their purine and pyrimidine base isolation methods could be criticized in that their calculations of the total recovery of the phosphorous content were presumed to be uniform across all bases.

In contrast, Daly had used a method of DNA base purification showing differences in DNA phosphate recoveries during nucleotide base preparations and took these differences into account, making their base measurements more accurate than had been seen before. After studying the controversial issue herself of the Levine-Steudel-Bass-Mandel school of thought (pro-tetranucleotide hypothesis) versus the Gulland-Chargaff school (anti-tetranucleotide hypothesis), Daly found that the equimolecular proportion of the bases as predicted by the tetranucleotide hypothesis were not, in fact, the case. She thus accurately determined that the tetranucleotide hypothesis was, in her word, “untenable.”

The third question that Daly addressed was related to the nucleic acid composition of various living sources. Namely, she was curious whether the purine-pyrimidine compositions differed in diverse organisms’ cells, tissues, and organs. After studying the various DNA sources closely, considering the correct DNA phosphate concentrations, of course, Daly found that the nucleic acids did not differ considerably in their compositions of purines and pyrimidines. The trio of investigators published the work together in the Journal of General Physiology with Daly as the first author in May of 1950, three years before Watson, Crick, and Franklin would reveal the structural nature of DNA.

5) Cholesterol and sugar—I can remember hearing many scientists say that sugar is “so sweet and yet so deadly.”  Did she do the very preliminary work in this realm?

As many informed individuals know, cholesterol can form plaques with fatty acids in the arteries (atherosclerosis), narrowing these blood vessels, leading to lowered blood flow, and delivering less oxygen to the tissues such as the heart. See Figure 3. This medical condition is known as coronary artery disease or atherosclerotic heart disease. Regarding sugar, it is known to be associated with diabetes type 2 and hypertension, the latter of which is characterized by high blood pressure.

File:2113ab Atherosclerosis.jpg

Figure 3. Atherosclerosis diagram and tissue section.

Dr. Daly was one of the first investigators to experimentally demonstrate the relationships between cholesterol, sugar, hypertension, and coronary artery disease. Specifically, Daly and colleagues provided some of the first evidence that the onset of high blood pressure could lead to atherosclerosis. Further, Daly experimentally showed that a diet laden with high amounts of cholesterol could lead to clogged blood arteries. Daly considered hypertension into the atherosclerotic equation. She found that the pathological condition of the cholesterol-clogged arteries worsened with increasing levels of hypertension. This association was a profound finding, and Daly was a prominent investigator in the studies that supported the notion with clinical and physiological data.

Daly’s first foray into the area of sugar and cholesterol studies occurred in the late 1950s, in which she was part of an investigative team that consisted of medical research scientists like herself. Together the research team published a groundbreaking article. In the 1958 paper, published in the Journal of Experimental Medicine, Daly and colleagues showed that in laboratory rats with induced hypertension, the condition was further intensified after the rats were provided a diet laden with high cholesterol. The so-called “atherogenic” diet-fed laboratory rats showed the telltale pathological signs of atherosclerotic plaque lesions in the arteries lining their hearts. See Figure 3. The investigators found the physiologically determined signs of exceptionally high cholesterol levels in the blood of these laboratory animals. This condition is called hypercholesterolemia. The research team also observed in the rats an excessive concentration of blood lipid, known as hyperlipidemia. Lastly, the carcasses and especially the livers of the laboratory rats showed excessive levels of cholesterol. These early medical scientists, Daly among them, had seen the dietary cholesterol end up in virtually all internal tissues of the rat body. To the research team, one surprising result was that these physiological data were evident despite the concomitant observation that virtually all biosynthesis of cholesterol was stopped in its tracks in the bodies of the high-cholesterol-fed rats.

Later, when Daly considered the effects of high sugar levels, the hypertensive condition was aggravated. In one of these critical studies, Daly was the sole author of the article published in the prestigious American Journal of Physiology in 1976. She had evaluated the effects of aging and hypertension on the ability of the aorta in the laboratory rat to utilize glucose metabolically. Daly studied glucose utilization by measuring the conversion of sugar into lactate and carbon dioxide. She studied young versus older laboratory rats that had renal hypertension. She isolated the aortic blood vessels from these laboratory animals and incubated the tissues with radioactive glucose. Next, Daly measured the levels of carbon dioxide, lactate, and the concentration of lipids in the aortic tissues. The effects on glucose utilization by aging and hypertension were compelling. Daly demonstrated that glucose metabolism was enhanced in these hypertensive laboratory rats. This result and those of other studies performed by Daly were significant because she showed how heart attacks were possible in a physiological sense with sugar and cholesterol.

6) Cigarette smoke, cigarette smoking, and their impact on the lungs—again, she seemed to be before many others in making the connection—am I wrong on this?

Indeed, in the mid-1970s, Dr. Mary Daly participated in a groundbreaking discovery of an experimental animal model for evaluating the effects of chronic cigarette smoking. The new canine lab model involved beagle dogs of the species Canis familiaris. The novel experimental animal model permitted Daly and her colleagues to evaluate how cigarette smoking affected the lungs’ structure and measure the function of the pulmonary defense mechanism against inhaled cigarette smoke.

In the experimental laboratory smoking system, the dogs inhaled cigarette smoke through a mouthpiece apparatus in which the smoke originated from lit cigarettes. The dogs were given periodic diluted doses of cigarette smoke for six months up to one year. Daly and her colleagues found that the cigarette smoke caused the formation of specific lesions in the central airways of the dogs and the membranes of their bronchioles. The dogs in the study also exhibited a specific proliferation of their so-called goblet cells in their airways from the inhaled cigarette smoke. Goblet cells are known for their propensity to secrete mucus into respiratory tracts, and an abnormally large quantity of these cells can produce excessive fluid in the airway, generating new pathophysiological conditions.

An inflammatory response from the cigarette smoke was observed in the dogs’ trachea epithelial cells, a condition known as tracheal basal cell hyperplasia. Physiologically speaking, after the dogs were exposed to cigarette smoke, the macrophages of these lab animals were impaired in their ability to undergo normal phagocytosis behavior against bacteria. See Figure 4. Impairment of such macrophage cell activity by smoke exposure could lead to increased frequencies of infection. Furthermore, the cigarette smoke caused the so-called mucociliary axis machinery to be impaired, triggering reduced clearance of trapped foreign materials from the airway. Daly and her colleagues also noticed an infiltration of inflammatory cells in the dogs’ peribronchiolar tissues after the cigarette smoke exposure.


Figure 4. Stages of normal phagocytosis.

The choice made by these investigators in using dogs was a fortuitous one because the pathology of chronic bronchitis after cigarette smoke exposure was quite similar to the pathophysiology that would be seen in humans. Daly and her co-authors published the new work in a journal called American Review of Respiratory Disease in June of 1977. In later years, chronically inflamed tissues would be correlated with a higher incidence of pulmonary disorders and cancer.

7) Hypertension, the cardiac system—cholesterol and clogged arteries—what did she maintain in this area? Her findings?

As we established in our discussion above, hypertension involves high blood pressure, which is pathological and associated with expanded incidences of heart attacks and coronary artery disease. We also established how Daly examined the relationships between sugar and these sorts of conditions. In 1958, Daly began her study mission in these areas by examining respiration in the aortas of induced hypertensive rats.

In this initial study, Daly focused her attention on cytochrome oxidase’s respiratory enzyme and compared its oxygen uptake activity between healthy versus hypertensive laboratory animals. See Figure 5 for an example of the structure of a cytochrome oxidase, called cytochrome C oxidase or Complex IV. In the respiratory chains of cells, the cytochrome oxidase enzymes play a role in oxidation-reduction and proton translocation across the membrane. As electrons are shuttled to oxygen across the respiratory chain’s complexes, the electrochemical gradient of protons generated can be used to make ATP for the cell’s living purposes.

To study the effects on respiration, Daly induced the hypertensive state in the rats in one of two ways. The first method was implanting a pellet within the skin layers containing desoxycorticosterone acetate and messaging the implant to release the agent, causing hypertension. The second technique involved surgically removing a kidney and then using a silver clip to constrict the renal artery of the animals. Daly measured blood pressure in the feet of the rats to confirm the hypertension induction.

Next, Daly removed the rat aortas that belonged to healthy versus hypertensive animal groups. In the isolated aortas, Daly measured the cytochrome oxidase enzyme activities and oxygen consumption. She found that in both cases (healthy and hypertensive), the biochemical activities were enhanced in the hypertensive lab animals. In early February of 1959, Daly published her findings. She was the first author of the article that appeared in the Journal of Experimental Medicine. The paper concluded that the aortas of hypertensive individuals had higher respiratory rates due to the involvement of additional muscle and connective tissues to form thicker aortas and from the more significant activity of the biochemical machinery inside the cells of thicker aortas undergoing high blood pressure.

File:Cytochrome C Oxidase 1OCC in Membrane 2.png

Figure 5. Cytochrome C Oxidase.

In 1963 Daly turned her attention to cholesterol levels and their biosynthesis in the aortas of hypertensive rats. She had been aware of the problem encountered in the aortas of hypertensive individuals in which atherosclerosis was more pronounced than in non-hypertensive subjects. The aortas stressed by hypertension were believed to be damaged by plaque lesions and abnormally high blood pressure, leading to alterations in the normal flow of blood through the arteries. During the early 1960s, the turbulent blood flow through the atherosclerotic aorta was hypothesized to abnormally retain lipids and cholesterol in the aortic walls.

Daly considered this cholesterol phenomenon experimentally in the blood and aorta of hypertensive laboratory rats. She observed that in these laboratory rats, the cholesterol levels were dramatically higher in the aorta and the blood sera than in healthy rats. The hypertensive rats also had increased rates of cholesterol synthesis in their aortas. In this case, the observed enhancement of cholesterol synthesis was likely due to the need to form new, more rigid aortic tissue to accommodate the induced hypertensive state.

In contrast, in the feeding studies of 1958, Daly saw little cholesterol biosynthesis, as the high dietary levels of cholesterol seemed to supply that need. Today, we know that the membranes of animals and humans are laden with cholesterol to regulate membrane fluidity as a normal process of sterol metabolism. Thus, to enlarge the aorta tissue (hypertrophy), new membranes with cholesterol are needed. Daly published her new results in the Journal of Clinical Investigation in October of 1963.

Afterward, Daly and several of her colleagues followed up on the cholesterol synthesis phenomenon by measuring the biochemical incorporation of radioactive carbon-14 acetate, a precursor to cholesterol, into the tissues of the aorta. They found that the aortas of hypertensive rats incorporated the radioactive tracer more quickly into cholesterol than in so-called normotensive rats. The enhanced rates of cholesterol in hypertensive tissues were confirmed biochemically. Daly published the supporting metabolic data in 1965 in the Journal of Laboratory and Clinical Medicine.

In the early 1970s, Daly investigated the relationship between cholesterol and lipids in the hypertensive tissues of the rat aortas. She showed that in these hypertensive tissues, a lipid derivative of cholesterol, called cholesterol ester, a storage form of the molecule, originated in the blood plasma and ended up in high concentrations within the aortas. Thus, Daly showed that atherosclerosis developed by transferring cholesterol-lipid complexes from the blood plasma to the blood vessels during hypertension. Daly published these remarkable effects of lipids and cholesterol in rat aorta as a single author in Circulation Research in September 1972.

In the mid-1970s, Daly focused on atherosclerosis and hypertension by concentrating on specific enzymes within intracellular lysosomal vesicles of diseased aortas in Rhesus monkeys. Daly and her colleagues found that in the diseased aorta, the lysosomes showed a significant increase in acid phosphatase activity, which removes phosphates from molecules. In the same tissues, Daly observed an increase in the enzyme activity of β-N-acetylglucosaminidase, which removes molecules of N-acetylglucosamine from larger sugar-based molecules of carbohydrates of the aorta. See Figure 6.

Furthermore, Daly and her collaborators found that the concentrations of the lysosomes were increased in coronary blood vessels and an abnormal cellular enhancement of cholesterol amounts in heart vasculature. In April of 1975, Daly and co-workers published these results in Circulation Research. The article would be Daly’s last on the topic of hypertension.


Figure 6. N-acetylglucosamine is also called N-Acetyl-α-D-glucosamine.

8) In 1986, Daly retired from the Albert Einstein College of Medicine—what would you say were her significant contributions?

Dr. Marie Daly had a remarkable career spanning over four decades. She would make meaningful scientific contributions to the biochemistry of nuclear histone proteins, cellular mechanisms of the translational machinery, atherosclerosis, cigarette smoking, hypertension, arterial vasculature physiology, cholesterol metabolism, and creatine biochemistry in muscle.

The latter work of creatine metabolism in muscle would be her last before her retirement. She had characterized creatine formation by studying the energetic behavior of guanidinoacetate methyltransferase, the last enzyme responsible within the pathway for creatine synthesis in cancer cells grown in culture. In a real sense, these disparate scientific investigative fields indicate that Daly can be rightly considered a Renaissance woman of science.

Another pioneering achievement by Dr. Daly lies in the fact that she was the first female African American in the U.S. to garner the coveted Ph.D. in the field of chemistry. Her Ph.D. thesis topic was on the enzyme amylase from the pancreas and the enzyme’s effect on corn starch. One medical news source estimates that only about two percent of African American women held a college degree when Daly’s acquisition of the doctorate occurred.

In academia, Daly was a dedicated educator who taught courses in biochemistry for decades at Howard University and Columbia University in their College of Physicians and Surgeons. Further, Daly is considered a champion mentor who encouraged her students and advisees to enter educational programs in graduate and medical schools. As an influential academic advisor, Daly enhanced the enrollments of countless students in science education. Along these mentorship lines, Daly established a scholarship program at Queens College for minority students in the sciences in honor of her father, who had sacrificed his own higher educational career aspirations because of a lack of funding.

9) Just before the turn of the 20th century, she was acknowledged and recognized as one of the top 50 women scientists of all time. Why have we not heard more about this trailblazer?

The reasons for the late recognition of Dr. Daly and her achievements are uncertain. Interestingly, it has been reported that even James Watson had acknowledged Daly’s contribution to nucleic acid biochemistry in one of his addresses regarding his Nobel Prize. Daly’s 1953 paper cited by Watson and discussed above dealt with the biological role of ribonucleoprotein in the cellular translational mechanism. Her article was explicitly referenced in Watson’s Nobel Lecture, delivered on the evening of December 11, 1962. Unfortunately, however, such an early well-documented recognition of Daly’s published work by one of the world’s leading experts on nucleic acid chemistry would be the climax. In his memoir, Francis Crick refers only to Alfred Mirsky, Daly’s 1953 co-author, rather than Daly herself or any of her work.

Furthermore, in Robert Olby’s thoroughly documented 1974 treatise on The Path to the Double Helix, Mirsky was widely credited for many of his opinions regarding the DNA structure discovery, even his incorrect opinions on the matter. Mirsky is mentioned about 60 times in Olby’s book. No mention of Daly occurs in the same book—not even in a later edition, published twenty years later. Thus, influential early scientists and historians of the fledgling field of molecular biology may have missed the mark by omitting the scientific contributions of Daly early on during the 1960s and 1970s.

The relative resurrection in more recent times of Dr. Marie M. Daly as a quintessential scientific contributor to so many biochemical, physiological, and molecular biological areas may be due to the efforts of several grassroots movements. For example, the Chemical Heritage Foundation, an offshoot of the Science History Institute, and allied with the Association for Women in Science, established a program devoted to Women in Chemistry and featured Daly in one of their historical biographical profiles. Beginning in the 1990s, several books that dealt with the topic of African American scientists featured Daly and her life and achievements. While no full-length biography of Daly has been published to date, one anticipates that the need to know her story will be more deeply felt and will no doubt be a driving force.

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