U n i v e r s i t y o f N e w S o u t h W a l e s

Heroes of Medical Science: Suzanne Cory z5017074FoundationsMFAC1501Word Count:

24 March 2014

Z5017074

Table of Contents

INTRODUCTION 3

PART 1: SUZANNE CORY AND HER CONTRIBUTION TO THE DISCIPLINE OF MOLECULAR BIOLOGY 3 THE DISCIPLINE OF MOLECULAR BIOLOGY, ONCOLOGY AND IMMUNOLOGY

BRIEF BIOGRAPHY

CORY’S CONTRIBUTION TO MOLECULAR BIOLOGY

PART 2: AN EVALUATION OF SUZANNE CORY’S WORK AND THE STATE OF MOLECULAR BIOLOGY FROM 1970-2000 6 MOLECULAR BIOLOGY FROM 1970-2000EVALUATION OF CORY’S WORK TO MOLECULAR BIOLOGY

PART 3: REFLECTION 8

APPENDIX 4

2

Z5017074

Introduction

Science and its progression is attributed to the heroes who have toiled through countless experiments to bring us our knowledge today. Suzanne Cory is one of these heroes and has played a pioneering role not just with her research into the field of molecular biology, but also as a remarkable role model for girls and women in science. This report seeks to encapsulate Cory’s biography and her contribution to medical science with its subsequent impacts on immunology, oncology and medical research. It will also define molecular biology, the state of knowledge at the time of Cory’s research and its underlying importance to the practice of medicine. While Cory’s inspiring position as a role model for female scientists is just as important as her scientific research, I will not be outlining that in my report due to word constraints(Suzanne, 2013). Finally, I will be reflecting on my process of learning in this report.

Part 1: Suzanne Cory and her contribution to the Discipline of Molecular Biology

The Discipline of Molecular Biology, Oncology and Immunology

Molecular biology is the study of the molecules that are associated with living things, particularly proteins and genetic material such as DNA and RNA (Press, 2010). It is an essential discipline for understanding the structure and function of the basic unit of life, the cell. This knowledge in turn, is vital for the understanding of pathology, anatomy, embryology and physiology. (Asifa et al., 2011)

Oncology has been defined as the study and treatment of tumours (abnormal growths)(Chadd, Jean, & Edward, 1999; Press).

Immunology is the discipline associated with the immune system and all its phenomena(Press).

3

Figure 1. A cell undergoing mitosis in the anaphase, an important aspect of molecular biology.

Z5017074

Brief BiographySuzanne Cory was raised in Victoria, Australia and attended high school at Canterbury Girls’ High School and the University High School before enrolling at Melbourne University(Tattam, 2000). It was during her undergraduate studies that Cory became fascinated with DNA, a relatively new discovery at the time. Following her Masters degree, Cory travelled to Cambridge University in England to work in the MRC Laboratory of Molecular Biology (MLB); then known as the “mecca of molecular biology”(Dennis, 2002). Here she met several Nobel Prize winners including Professor Francis Crick, the co founder of the molecular structure of DNA, reinforcing “that there were no half-measures in science – the commitment has to be all or nothing”(Dennis). She also met her husband, Professor Jerry Adams, in Cambridge and together the pair would produce some of the most astounding work in immunology, oncology and genetics(Tattam).

Following her many discoveries in the years to come, Cory was appointed as the first female in the position of Director of WEHI in 1996 as well as the Royal Medal of the Royal Society in 2002(Dennis). She also has a high school (the Suzanne Cory High School) named after her("Professor Suzanne Cory-AC, PhD, PresAA, FRS," 2014). She currently lives with Adams and her two children.

Cory’s contribution to Molecular Biology

Cory’s research has been numerous with at least 162 research articles where she has been referenced as the author. Following her work in Cambridge, Cory and Adam began work in the University of Geneva(Tattam). They studied the genetic sequence of RNA, specifically the R17 bacteriophage’s RNA in order to gain a greater understanding of RNA messaging("Professor Suzanne Cory-AC, PhD, PresAA, FRS," 2014). The pair then returned to Australia to begin work in the Walter and Eliza Hall Institute (WEHI) and introduced gene cloning technology to the relatively new field of molecular biology in Australia(Dennis). Using this technology, Cory and Adams cloned the genetic code of the immune system and discovered how humans are able to produce antibodies with staggering possibilities; the genes for antibodies are actually encoded as separate sections which are able to be combined in incredible diverse ways(Tattam).

Cory and Adam followed up their research by then studying cancer, specifically Burkitt’s lymphoma. The pair were able to deduce that Burkitt’s lymphoma started off as chromosomal translocation, that is, the incorrect arrangement of antibody genes(Tsujimoto, Cossman, Jaffe, & Croce, 1985). Furthermore this “mixing” of the gene code would activate the MYC oncogene (cancer-causing gene) that eventually developed into the blood cancer(J. M. Adams et al., 1985). They provided significant

4

Figure 2. Dr Jerry Adams, Cory's husband and research partner.

Z5017074

evidence by using their new technology and modifying the antibody genes in mice to create mice with lymphomas(J. M. Adams et al., 1985).

Perhaps her most famous work was the explanation of the BCL-2 family of proteins in molecular biology and pathology, specifically its role in cancer(Cory & Adams, 2002). Cory and Adams observed that this family of proteins were crucial in the life cycles of cells

because they acted as regulators of apoptosis (programmed cell death)(Suzanne, David, & Jerry, 2003). Specifically, these proteins were able to control apoptosis by inhibiting the signals that would tell a cell to being dismantling (Jerry M. Adams & Cory, 1998). Furthermore they touched on the “distant relatives” of the BCL-2 proteins that actually prevented apoptosis instead of promoting it. These discoveries were very influential and revolutionary at the time due to a high interest in the causes of cancer and cell life cycles(Hanahan & Weinberg, 2000). Cory and Adams further extrapolated their work and explained the role of BCL-2 in cancers(Jerry M. Adams & Cory, 1998). Prior to Cory’s work, all cancers were found to have originated from excessive cell growth(Hanahan & Weinberg, 2000). Cory showed that human follicular lymphoma was caused by cells that had unnatural life and linked this back to the workings of the BCL-2 protein(Jerry M. Adams & Cory, 1998; Dennis, 2002).

5

Figure 3. Three of the proteins belonging to the BCL-2 family.

Z5017074

Part 2: An Evaluation of Suzanne Cory’s work and the state of molecular biology from 1970-2000

Molecular biology from 1970-2000

In the 1970’s, there were very few molecular biologists in Australia(Tattam, 2000). In fact, when Cory and Adams returned to Australia from their work in Canada they helped introduce the new recombinant gene technology into Australia (Dennis, 2002). The timeline below is a good illustrator of the level of knowledge that scientists had about just the MYC oncogene from 1979 to 2007(Natalie & Linda, 2008). Clearly the field of molecular biology was extremely broad and scientists at the time of Cory’s work had only just began to brush the surface. At the time Cory’s research in the field of oncology and immunology was a relatively new specialty for molecular biology. Her work was conducted in a time when the genetics of cancer was mostly unexplored territory (Natalie & Linda, 2008).

6

Figure 4. A timeline of MYC research.

Z5017074

Evaluation of Cory’s work to Molecular Biology

Cory contribution to molecular biology, oncology and immunology has been numerous and crucial.

Cory’s work in identifying the chromosomal translocation of Burkitt’s lymphoma and the importance of oncogene MYC was part of the pioneering into the genetics of cancers and how they propagated at a molecular level (Hanahan & Weinberg, 2000; Natalie & Linda, 2008; Richard & Andreas, 2008). Indeed her well-documented experiments of mice with the MYC oncogene has been cited 652 times according to Scopus (J. M. Adams et al., 1985), showing the remarkable impression left by Cory and Adams. Furthermore, Natalie and Linda (2008) directly refer to the pair’s work on Burkitt’s lymphoma as a foundation for subsequent understanding in MYC oncogene function, behavior and possible treatments for cancers caused by this gene. All of the above sources indicate that Cory’s early work in molecular biology was essential to today’s knowledge of immunology and oncology.

Building upon her work in genetics and chromosomal translocation, Cory’s discovery of the BCL-2 family of proteins has been regarded as her most outstanding contribution (Dennis, 2002; Tattam, 2000). Prior to Cory and her team’s discovery of the BCL-2 proteins and their function, scientists thought cancers only developed through the multiplication of malignant cells (Dennis, 2002; Richard & Andreas, 2008). Cory was able to discover and show that cancer could also be caused by cells having unnatural lifespans instead; a revolutionary idea in oncology at the time(Jerry M. Adams & Cory, 1998). This paper Furthermore Cory was able to link this idea to the BCL-2 proteins that monitored apoptosis (programmed cell death), providing potential leads for cures and treatments (Jerry M. Adams & Cory, 1998; Hanahan & Weinberg, 2000). Tattam (2000) provides glowing reviews and praise from scientists of Cory’s contribution to immunology and oncology, including Nobel Laureate David

7

Figure 5. The tree of MYC knowledge. This is a clear indicator that Cory’s research into Burkitt’s lymphoma had a significant impact on understanding MYC and its role in cancer.

Z5017074

Baltimore’s (Medicine) who stated: “… their discovery of the MYC translocation in Burkitt lymphomas was a crucial observation and the discovery that BCL-2 can counter cell death was striking.” Clearly, Cory’s investigations into this protein family has been significant to say the least. It is now known that there are several growth patterns associated with cancer, of which evasion of apoptosis is one (Hanahan & Weinberg, 2000). While Cory’s work was outstanding, there is still much to be answered and understood. Cory herself acknowledges that the topic is complex and fundamental concerns such as the exact molecular mechanisms of BCL-2 need to be analysed (Jerry M. Adams & Cory, 1998; Dennis, 2002; Tattam, 2000).

In summary, it is evident that Cory produced plenty of important breakthroughs and advances in her research with Adams. According to the Scopus database, her 162 papers have been cited a staggering 20765 times, allowing us to infer that her work has had significant impacts on the scientific community as a whole. As shown above, it has been acknowledged that her work is leading eventually to the complete understanding and perhaps even cure for some of the cancers associated with the BCL-2 proteins and the MYC oncogenes. These will be outstanding breakthroughs in the practice of medicine.

8

Z5017074

Part 3: Reflection

Beginning this assignment, I honestly had no idea what I was in for. I had very little knowledge about any of the scientists apart from Graeme Clark but decided to choose Suzanne Cory instead. This was primarily because I wanted the challenge of researching and learning a completely new topic without prior knowledge. I’m actually very glad I picked Cory because she hasn’t just been a hero of medical science, but also a hero and role model for women and girls interested in science everywhere. I feel that that I have a greater understanding of molecular biology and its importance in my studies to become a doctor. I remember being able to understand a pathology lecture involving apoptosis in my third week because of my research in this field while studying Cory’s work.

As a typical high school leaver, my first point of call when researching for this assignment was the use of Google and various medical dictionaries. Using these helped me gain a general outline of the topic at hand, but I was also conscious that my online sources weren’t necessarily reputable. I had difficulty using databases to find scholarly material at first, but following the library research tutorials, I began to use Medline, Scopus, Cochrane Library and the Oxford Reference Site. I also had trouble learning how to reference properly, but like above, the library research tutorials really helped me overcome this obstacle. Those two examples above made me realize how difficult “self-directed learning” was, but I also gained new skills which I look forward to applying in future assignments.

My biggest trouble was having too many words. An example of this was not being able to explain Cory’s significance as a highly-acclaimed Australian female scientist. I had initially provided a 300 word section on her impact as a role model but decided that this report was primarily about the science behind her research. I had to reluctantly cut this out, but the knowledge and respect for her work has given me a new perception about contemporary science.

In SG, I handed my draft in to Wendy who was also completing a report on Suzanne Cory. While reading his work, I began to reflect on my own essay. I was inspired by Wendy’s ability to write fluidly which I felt my essay didn’t have. Wendy commented that my essay required deeper understanding in the evaluation part of Cory’s work and that my introduction was too brief. Taking both Wendy’s and my own criticisms, I returned to my draft and reconstructed my introduction as well as the evaluation section. I have learnt that peer reviewing is essential because we can become blind to our faults unintentionally. Peer reviewing will become a necessary part of my assignments in the future.

9

Z5017074

References

Adams, J. M., & Cory, S. (1998). The Bcl-2 Protein Family: Arbiters of Cell Survival. Science, 281(5381), 1322-1326. doi: 10.2307/2896432

Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., . . . Brinster, R. L. (1985). The c- myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature, 318(6046), 533. doi: 10.1038/318533a0

Asifa, A., Elaine, F., Tim, M., Reuben, J. S., Daniel St, J., Andreas, S., . . . Marino, Z. (2011). A decade of molecular cell biology: achievements and challenges. Nature Reviews Molecular Cell Biology, 12(10), 669. doi: 10.1038/nrm3187

Chadd, E. N., Jean, M. T., & Edward, V. P. (1999). MYC oncogenes and human neoplastic disease. Oncogene, 18(19), 3004. doi: 10.1038/sj.onc.1202746

Cory, S., & Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or- death switch. Nature Reviews Cancer, 2(9), 647.

Dennis, C. (2002). Suzanne Cory. Nature medicine, 8(3), 203. Hanahan, D., & Weinberg, R. A. (2000). The Hallmarks of Cancer. Cell, 100(1), 57-70.

doi: 10.1016/S0092-8674(00)81683-9Natalie, M., & Linda, Z. P. (2008). Reflecting on 25 years with MYC. Nature Reviews

Cancer, 8(12), 976. doi: 10.1038/nrc2231Press, O. U. (2010). Concise Medical Dictionary: 'Oxford University Press'.Professor Suzanne Cory-AC, PhD, PresAA, FRS. (2014). from

http://www.suzannecoryhs.vic.edu.au/professor-suzanne-coryRichard, J. Y., & Andreas, S. (2008). The BCL- 2 protein family: opposing activities that

mediate cell death. Nature Reviews Molecular Cell Biology, 9(1), 47. doi: 10.1038/nrm2308

Suzanne, C. (2013). Institutions: Australian academy is fair to women. Nature, 497(7450), 439. doi: 10.1038/497439c

Suzanne, C., David, C. S. H., & Jerry, M. A. (2003). The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene, 22(53), 8590. doi: 10.1038/sj.onc.1207102

Tattam, A. (2000). Suzanne Cory: combining individuality with teamwork. Lancet, 355(9210), 1164.

Tsujimoto, Y., Cossman, J., Jaffe, E., & Croce, C. M. (1985). Involvement of the bcl-2 gene in human follicular lymphoma. Science, 228, 1440.

10

Search Strategy

Topic Source/Database Search Strategy Hits/Results Relevant article(s) selected Comments

Biographical materials on Suzanne Cory

UNSW Library 1. Suzanne Cory 1871 Suzanne, C. (2013). Institutions: Australian academy is fair to women. Nature, 497(7450), 439. doi: 10.1038/497439c

Dennis, C. (2002). Suzanne Cory. Nature medicine, 8(3), 203

Tattam, A. (2000). Suzanne Cory: combining individuality with teamwork. Lancet, 355(9210), 1164.

Excellent sources for the biography of Suzanne Cory. I found them extremely useful and well detailed.

Original Papers by Suzanne Cory

Medline 1. Cory S.au2. BCL-23. 1 and 2

167 Adams, J. M., & Cory, S. (1998). The Bcl-2 Protein Family: Arbiters of Cell

I found Medline quite difficult to use because of the specificity

Z5017074

Survival. Science, 281(5381), 1322-1326. doi: 10.2307/2896432

Cory, S., & Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or- death switch. Nature Reviews Cancer, 2(9), 647.

required. I did find useful research papers but I prefer to use Scopus.

Original Papers by Suzanne Cory

Scopus Author Search:Cory S.

1. Documents2. Citations

162 Adams, J. M., & Cory, S. (1998). The Bcl-2 Protein Family: Arbiters of Cell Survival. Science, 281(5381), 1322-1326. doi: 10.2307/2896432

Adams, J. M., Harris, A. W., Pinkert, C. A., Corcoran, L. M., Alexander, W. S., Cory, S., . . . Brinster, R. L. (1985). The c- myc

All excellent articles that show the work done by Cory. This is just a snapshot of her work and contained many complex details which required extra work. Overall citation count of Cory was 20766 over 162 documents.

12

Z5017074

oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature, 318(6046), 533. doi: 10.1038/318533a0

Cory, S., & Adams, J. M. (2002). The Bcl2 family: regulators of the cellular life-or- death switch. Nature Reviews Cancer, 2(9), 647.

Suzanne, C., David, C. S. H., & Jerry, M. A. (2003). The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene, 22(53), 8590. doi: 10.1038/sj.onc.1207102

Overview of Medline 1. Molecular 194 Asifa, A., Elaine, F., Tim, This was a tough

13

Z5017074

molecular biology at the time

Biology/2. Limit 1 to “review

articles”3. Decade.m.p.4. Overview.m.p.5. 1 and 2 and 36. 1 and 2 and 4

M., Reuben, J. S., Daniel St, J., Andreas, S., . . . Marino, Z. (2011). A decade of molecular cell biology: achievements and challenges. Nature Reviews Molecular Cell Biology, 12(10), 669. doi: 10.1038/nrm3187

find.

Overiew of cancer treatment

Nature Reviews Cancer 556 Natalie, M., & Linda, Z. P. (2008). Reflecting on 25 years with MYC. Nature Reviews Cancer, 8(12), 976. doi: 10.1038/nrc2231

Good journal for finding reviews on any topic in medicine.

14