|Martha Chase in 1953|
The subject of today's post is the Dr. Martha Chase of "Hershey-Chase" fame. Her name will be forever associated with what is considered to be the definitive experiment showing that DNA, not protein, is the inheritable genetic material. Let's rephrase that, because it is an important discovery that we take for granted today: Hershey and Chase showed that genes are made of DNA, not protein. As you can imagine, that was a big deal. Before that, many scientists thought that DNA was frankly not very important and pretty uninteresting. Many thought that genes were instead made out of protein. Hershey and Chase forever changed that with a simple series of experiments.
We'll get into the historical background of the experiments in a moment. If you've read some of the previous posts in this series, you can probably guess that the reason we're talking about Chase is that, despite this impressive experiment that bears her name, Martha Chase watched Alfred Hershey receive a Nobel Prize in 1969 for the discovery, while she sat on the sidelines.
Was this an example of gender bias, or simply a case of giving credit to the more deserving half of the pair? Let's talk about the facts of the case. We'll go through the Hershey-Chase experiment and the somewhat tragic life of a legendary geneticist after the jump.
I want to first mention that one fact that sets Chase apart from some of the previous women we discussed in our series is that Martha Chase's career was cut short by personal set-backs and tragedy. Chase helped to design one of the most elegant experiments in the early history of molecular biology. Hershey and Chase set off the race to discover the structure of DNA. However, that wasn't enough to prevent her scientific career from fizzling out. In contrast, Lise Meitner, Jocelyn Bell Burnell, and Chien-Shiung Wu all had impressive scientific careers and received many honors despite losing out on the Nobel. Martha Chase's story is a little more tragic. It's also very hard to find much information about her life compared with the other women we've already discussed on this blog. Martha Chase is more of an enigma.
|Phages infecting a bacteria cell|
The actual Hershey-Chase experiment was conducted in 1952, between her time in Wooster and California. She started working as a research technician in the lab of Dr. Alfred Hershey at Cold Spring Harbor Laboratory on Long Island, NY in 1950 at the age of 21. Hershey and many other prominent researchers at Cold Spring Harbor were working on bacteriophages (or just phages, for short), which are viruses that can infect bacteria (discussed in a previous blog post). These researchers, including Salvador Luria and Max Delbruck, who we will mention a bit later, became known as "The Phage Group." The work they did with phages helped to identify many of the basic principles of cell and molecular biology.
Because phages infect bacteria and turn them into "factories" for producing more phages (just like viruses that infect your cells use them to make more virus), researchers knew that bacteriophages transmitted some sort of genetic information (ie, the "blueprints" for new phages) to the bacteria when they infected them. Scientists at this time were thus trying to understand genetic inheritance by studying phages and how they transmit this genetic information to their bacteria hosts. From electron micrographs like the one shown above, scientists also knew that phages did not completely enter the bacterial cell. It was hypothesized that they injected something into the bacteria cell, using their tale almost like a hypodermic needle. If only the researchers could figure out what it was that they injected, they knew that there must be some genetic material in there.
Many biologists in the first half of the 20th century believed that the genetic material of cells had to be protein. This idea partly dated back to a scientist named Phoebus Levene. Pheobus Levene made several great contributions to biochemistry; he discovered both ribose sugar (the 5-carbon sugar component of RNA) and deoxyribose sugar (the 5-carbon sugar component of DNA). However, in 1910, Levene proposed an incorrect structure for DNA (called the tetranucleotide structure) that made the molecule seem too simple to be able to carry any sort of complex information with in it.
Hershey and Chase took advantage of the fact that protein and DNA have different chemical compositions. While the structure of DNA was not known exactly, it was still known that DNA contains phosphorus (P) atoms but no sulfer (S) atoms. Protein, on the other hand, contains sulfur (S) atoms within in the amino acids methionine and cysteine (amino acids are the building blocks of proteins). Protein does not contain phosphorous except under certain circumstances when certain enzymes (called kinases) add phosphate groups (which contain P atoms) onto certain proteins. This process is called phosphorylation. But, even then, the P content of proteins is much lower than the P content of DNA. For the purposes of this post, you can consider proteins to be phosphorous (P)-free and consider DNA to be sulfur (S)-free.
|The Hershey-Chase Waring Blender|
They then took the protein-labeled or DNA-labeled phages and infected more E. coli bacteria. They then put the bacteria/phage mix into a Warring blender to sheer-off the parts of the phages that remained stuck on the outside of the bacteria. The did this carefully so as not to disrupt the bacteria themselves; they tried other methods before using the blender, at the suggestion of a fellow genetics researcher, Margaret McDonald. The Warring blender they used, a not-very-elegant steel model, will forever be famously known as an intricate component of the experiment.
After blending their bacterial/phage cultures, Hershey and Chase could then separate out the bacteria from the phages and left over phage parts in a centrifuge. A centrifuge spins a sample to separate things based on a combination of size and density; when Hershey and Chase centrifuged their test tubes containing bacteria and phages, the bigger, heavier bacteria sank to the bottom of the tube (in what is called the pellet) while the phages remained at the top (in what is called the supernatant). This allowed them to separate out the bacteria and phages and look at how much radioactivity transferred from the original radioactive phages to the bacterial cells.
What they found was that the phages that had radio-labeled (P-32-labeled) DNA had passed this radioactivity on to the bacterial cells, while the phages that had radio-labeled (S-35 labeled) protein did not made the bacterial cells radioactive. Almost 80% of the radioactive DNA was transferred from the bacteriophages to the cells; almost none of the radioactive protein transferred to the cells.
|The Hershey-Chase Experiments, in a nutshell|
Now, it is important to note that Hershey himself originally believed that genes must be made of protein; Hershey initially wanted to disprove the original experiments of Avery, MacLeod, and McCarty. However, when Hershey and Chase rechecked their data and repeated their experiments, they found that the results were clear, repeatable, and irrefutable. In science, you have to be willing to sometimes admit to yourself that your ideas are wrong. But, likewise, a fun part of science is being able to form new ideas based on new facts at hand. Hershey was converted to the DNA camp.
While the experiment and its results were fairly simple, the impact was enormous. This intensified the race to determine the molecular structure of DNA. James Watson, co-discoverer of the DNA double helix, wrote:
|Martha Chase and Alfred Hershey, 1953|
Interestingly, Watson's near-immediate appreciation of the Hershey-Chase experiment was not widespread. In his book, The Double Helix, Watson wrote about his experience reading parts of Hershey's recent letter to him at a conference he attended. He wrote that "...almost no one in the audience of over 400 microbiologists seemed interested as I read long sections of the letter."
|Watson and Crick's DNA model|
Unfortunately for Martha Chase, though, the Hershey-Chase experiment marked the pinnacle of her scientific career; it was all downhill from there. Not long afterward in 1953, she left Cold Spring Harbor, though she frequently visited for summer meetings of the Phage Group. After leaving Hershey's lab, she worked briefly at Oak Ridge National Laboratory and at the University of Rochester. Then, in 1959, she went to the University of Southern California to study and perform research for her PhD, which she was awarded in 1964.
After receiving her PhD, however, Chase's scientific career seems to have fizzled out. As you may guess, being a woman didn't exactly help her in gaining the credit she deserved from her time at Cold Spring Harbor. She worked in laboratory jobs at USC for a while, but a combination of illness and being laid off from her research job in the late 1960s led to her moving back to Cleveland Heights and living with her father, Samuel Chase.
While at graduate school in the late 1950s, she had married a fellow scientist whom she had met in California, Richard Epstein, but they divorced after less than a year of marriage. According to a friend and colleague, Walter Szybalski, her divorce "left a deep scar." She never remarried and never had any children. Her divorce, coupled with her scientific career difficulties, apparently led to heavy drinking and smoking that helped create some health problems. Martha Chase died of pneumonia on August 8th, 2003. She was 75, and living in Lorain, Ohio, a Cleveland suburb. For decades before her death, she suffered from a form of dementia that robbed her of her short-term memory. She found joy in the simplicity of knitting. She was survived only by a younger sister. It is difficult to find much more detailed information about Martha's later life beyond that.
|Luria and Delbruck at Cold Spring Harbor, 1953|
Please note that I'm not trying to vilify Luria and Delbruck at all. They deserved a Nobel prize wholeheartedly. Their famous Luria-Delbruck experiment in 1943 demonstrated that genetic mutations in bacteria arise randomly in the absence of selection, not as a consequence of selection; thus, they showed that Darwin's theory evolution by which natural selection acts on random mutations is applicable to both complex organisms (like us) as well as single-celled organisms like bacteria. Their contributions were important and deserving. Hopefully I can discuss the Luria-Delbruck experiment in a future post.
However, the fact that Luria and Delbruck deserved a Nobel prize does not take away from the simple fact that Alfred Hershey received a Nobel Prize while Martha Chase did not. Like all of the other women in our series, we can't know with certainty how much a role her gender played in this decision, but it is hard to imagine that gender did not play some role. It is very likely that, because she was a research technician, she was viewed as simple a "set of hands" with which Hershey performed his experiments. We'll never know exactly how much her gender played in strengthening that viewpoint, but it is very likely that the fact that she was a woman made some believe that she had little intellectual input into the research.
Quite frankly, we don't have any evidence of what the relative intellectual contributions of Chase and Hershey actually were to the experiments, particularly since everyone involved is dead. Unfortunately, no witnesses remain. However, we already saw in the case of Chien-Shiung Wu that even a high-level, brilliant woman scientist could be viewed by the Nobel committee as merely "technical assistance" for the men running the show.
It is particularly interesting to note that it was not common practice in the 1950s to list laboratory assistants as authors on research publications; the paper that Hershey and Chase published in the Journal of General Physiology to describe their famous experiment had both of their names listed as authors. The fact that Hershey approved of putting Chase's name on this paper strongly hints that her role was more than just "technical assistance." Hershey's other actions don't suggest that he was overly generous with credit. In fact, Hershey himself provided perhaps the biggest insult to Martha Chase when giving his Nobel lecture, titled "Idiosyncracies of DNA Structure." In this lecture, he never even bothered to mention Martha Chase's name once.
Still, the fact remains that hundreds of thousands of high school and college students read and learn about the Hershey-Chase experiment every year in biology classes around the world. No one can ever take away that kind of recognition from Martha Chase; her name has reached a legendary status. Unfortunately, though, not all students probably learn that Chase was a woman, and I'm sure that far fewer learn anything about her somewhat tragic story.
Even Chase's New York Times obituary had a diminishing air to it, describing her life by the simple headline, "Martha Chase, 75, Researcher Who Aided in DNA Experiment." The article even went so far as to refer to Chase and Hershey as "Ms. Chase" and "Dr. Hershey," despite the fact that both had PhDs. Was that an example of the "Matilda Effect" or just a coincidental error? We'll never really know for sure.
Text and original color diagrams © 2013 TheMadScienceBlog; photographs are public domain.
Sources and Further Reading
- S. Aldridge. "The DNA Story." Royal Society of Chemistry. Available here.
- O.T. Avery, C.M. MacLeod, M. McCarty. "Studies on the Chemical Nature of the Substance Inducing Transformation of Pneumococcal Types." Journal of Experimental Medicine. 1944. 79:137-159. Available here.
- T.A. Brown. Genomes. 2nd Edition. Oxford: Wiley-Liss. 2002. Ch. 1. "The Human Genome" [Available here] and Ch. 4. "Studying DNA" [Available here].
- E. Chargaff. "Chemical Specificity of Nucleic Acids and the Mechanism of Their Enzymatic Degradation." Experientia. 1950. 6:201-209.
- Cold Spring Harbor Library. "Coming of Phage." Available here. [Contains the picture of the Waring Blender]
- K.E. Cullen. "Chase, Martha (1927-2003). American Geneticist." Encyclopedia of Life Sciences; Vol. 1. 2009. Infobase Publishing p. 182.
- M. Dawson. "Martha Chase Dies." The Scientist. 20 August 2003. Available here.
- A. Hershey and M. Chase. "Independent Functions of Viral Protein and Nucleic Acid in Growth of Bacteriophage." Journal of General Physiology. 1952. 36:39-56. Available here or here.
- S. Jaffe. "Defining DNA as the Hereditary Molecule." The Scientist. 24 Aptil 2004. Available here.
- S. Lavietes. "Martha Chase, 75, Researcher Who Aided in DNA Experiment." New York Times. Available here.
- W. Szybalski. Cold Spring Harbor Laboratory Oral Histories: "Walter Szybalski on Martha Chase." [Available here] and "Walter Szybalksi on The Hershey Chase Experiment." [Available here].
- J.D. Watson and F.H.C. Crick. "A Structure for Deoxyribose Nucleic Acid." Nature. 1953. 171:737-738. Available here.