A Practical Guide to Writing a Ruth L. Kirschstein NRSA Grant

Andrew D. Hollenbach

• Publisher: Academic Press
• Year: 2013
• eBook ISBN: 9780124202368
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

A Practical Guide to Writing a Ruth L. Kirschstein NRSA Grant provides F-Series grant applicants and mentors with insider knowledge on the process by which these grants are reviewed, the biases that contribute to the reviews, the extent of information required in an NRSA training grant, a deeper understanding of the exact purpose of each section of the application, and key suggestions and recommendations on how to best construct each and every section of the application. A Practical Guide to Writing a Ruth L. Kirschstein NRSA Grant is a solid resource for trainees and their mentors to use as a guide when constructing F30, F31, and F32 grant applications.  - Covers F30, F31, and F32 grant applications - Detailed overview of the review process - Key suggestions on how to best construct each section of the application - Includes a checklist of required items

Chapter 1

Ruth L. Kirschstein—The Woman and Her Legacy

Although thousands of people apply for the Ruth L. Kirschstein National Research Service Award (NRSA) training grants every year, few people actually know who Ruth was, what she accomplished in her career, and why these grants serve as her ongoing legacy to scientific training. This chapter provides a brief biography of Ruth L. Kirschstein including information about how her upbringing shaped her ambition and drive, her detail-oriented work as a pathologist leading to the creation of quality control standards for the polio vaccine, her dedication to mentoring and minority issues, her time at the National Institutes of Health (NIH) as the first woman to serve as a director of an NIH institute and as acting director of the NIH, and the lasting changes she implemented during her time at the NIH. A brief section is included describing the five different types of NRSA training grants (F30, F31, F31 Diversity, F32, and F33).

Keywords

Ruth L. Kirschstein; National Institutes of Health; national research service award; polio vaccine safety testing; deputy associate commissioner for science; National Institute of General Medical Sciences; minority access to research careers; honors undergraduate research program; National Center for Biotechnology Information

1.1 Ruth L. Kirschstein—A Brief Biography

The Ruth L. Kirschstein National Research Service Award (NRSA) training grants from the National Institutes of Health (NIH) are one of the most prestigious training awards given to predoctoral students and postdoctoral researchers in the United States. However, very few people actually know who Ruth L. Kirschstein was, what she accomplished in her career, and why these grants serve as her ongoing legacy to scientific training. Ruth Lillian Kirschstein, born in 1926, was the daughter of immigrants fleeing Jewish persecution in Russia whose original name, now forgotten, was changed to Kirschstein by a tired Ellis Island immigration official. She was raised in Brooklyn, the daughter of two teachers who instilled a love of learning in Ruth through a constant exposure to education and culture. As a result of the continual discrimination against Jews at the time, her parents encouraged Ruth to pursue her own interests in life, regardless of societal attitudes. Therefore, Ruth never realized or accepted that there was nothing that she could not accomplish once she set her mind to it. This familial environment also instilled high personal standards of excellence in Ruth. Although classically trained and accomplished in playing the French horn, she realized that her talent was limited and would not allow her to achieve the level of professional excellence that she desired. Therefore, she decided to follow her second love and pursue a career in medicine.

Ruth enrolled in Long Island University in 1943 and after completing college in 1947 applied to medical schools across the country. During this process, she fought gender and ethnic discrimination as a Jewish female, a bias that further exasperated the difficulty of being accepted into medical schools because of the quota system for admitting Jews to professional training programs. Not accepting defeat, she persevered and was finally accepted and enrolled at Tulane University Medical School in New Orleans in Los Angeles, becoming the only student from her Long Island University graduating class to be accepted into medical school. In a class of 109 new medical students, Ruth was one of only 10 women and the only Jewish female enrolled that year. She fully dedicated herself to becoming a doctor, eventually becoming interested in the study of disease and the effects of disease on the human body, which ultimately directed her to a career in pathology.

After completing medical school, Ruth elected to perform her yearlong internship in medicine and surgery at Kings County Hospital in Brooklyn, New York. This decision was made partly so that she could be near her new husband, Al Rabson, who was pursuing his own internship in New York, but also partly because of Kings County Hospital’s humanitarian mission. Kings County Hospital was, and still is, dedicated to providing care to all people regardless of their ability to pay, an attention to social justice that appealed to Ruth and influenced her entire career. During her internship, she was exposed to diseases and infections of all kinds, including tuberculosis, which she contracted and laid dormant in her for years. More importantly, this time in her career exposed her to many different aspects of medicine, training her to become adept at making on-the-spot decisions. A residency in pathology at Providence Hospital in Detroit followed Ruth’s internship until her husband was accepted into the pathology residency program in New Orleans. When Tulane University invited her to continue her pathology training, Ruth accepted.

A year later, in 1955, Ruth and her husband moved from New Orleans to Bethesda, Maryland, where Al accepted a research position in the National Cancer Institute (NCI) and Ruth completed a second year of pathology residency. Despite balancing work, home, and a newborn son, Ruth maintained a positive attitude and an incredible enthusiasm, serving as an excellent parent and role model for their son. At this time Ruth also began fighting for the rights of those commonly discriminated against. Her parents had always stressed and enforced the importance of social justice in their children, an awareness that was later influenced by Franklin D. Roosevelt’s fireside chats in which he made a call to help those in need. Further, her firsthand experience of racial segregation in the Deep South emboldened her desire to fight against the inequity of segregation and discrimination. Ruth brought this desire with her to the NIH where she fought for pay rises for deserving women and minorities in a system and at a time when these merit-based increases were not common.

During her residency, in addition to her clinical duties, Ruth would sometimes perform research studies with her husband. She had the chance to test out new instruments, such as the Coulter counter, which was invented at the NIH and is now a standard in hospital and cell biological laboratories. Further, in the mid- to late-1950s at the NIH, she was surrounded by a rich scientific environment during an exciting time in science. Marshall Nirenburg, PhD, who cracked the genetic code while at the NIH, had an apartment in the same building as Ruth and Al on the NIH campus. She also saw the development of the shift in cancer treatment from the standard of surgery and radiation to the newly-evolving method now known as chemotherapy, In particular the successful treatment of cancer with methotrexate.

After completing her residency, Ruth accepted a job with the NIH Division of Biologics Standards (DBS). As a “free-floating” pathologist, working with scientists in the NCI and the National Institute of Arthritis and Metabolic Disease (NIAMD), Ruth sought out and developed true collaborations where scientists worked with each other instead of for each other. In this collaborative capacity, as with many aspects of her career, Ruth demanded a great attention to detail. This is illustrated by the fact that despite a strong interest in studying the link between viruses and cancer, she refused to allow her name to be included as an author on the now-classic paper by Sarah Stewart, MD, PhD, and Bernice Eddy, PhD, in which they established the link between the SV-40 virus and animal tumors. This refusal to be included as an author on a seminal work derived from the fact that she felt not enough attention to detail had been used in the study. This absolute reliance on accuracy would pay off in her later work where she developed ultimate safety in the worldwide use of the polio vaccine.

Growing up in the mid-twentieth century, Ruth had firsthand knowledge of the fear engendered in the general population by polio, a fear the lasted until 1955 when Jonas Salk’s injectable polio vaccine was declared safe and effective. However, soon after the release of the vaccine, two batches generated from the same company were tainted with infectious virus, resulting in 40,000 illnesses, 50 cases of paralysis, and 5 deaths. It was determined that the cause was the unrealized incomplete inactivation of the virus by the method being used at the time to create a “safe” vaccine. To address this issue, the NIH developed a committee to develop new methods of inactivating the virus and hired Ruth to perform safety testing on the resulting vaccine. Tapping into her attention to detail, she developed the most effective and reproducible procedure for testing the safety of the vaccine in animals. Around this time Albert Sabin, MD, developed his oral polio vaccine that utilized an attenuated form of the virus, which had its own potential public health problems. In response to these concerns, the NIH developed a committee to develop standards for determining the safety of new batches of polio vaccine. Once again, through her hard work Ruth developed a method to test the safety of the vaccine in a manner that was reliable and reproducible. She taught this method to manufacturers around the world, subsequently becoming the standard by which all produced lots of polio vaccine were tested for safety.

As a result of the excellent work performed on vaccine safety, Ruth was named the chief of the DBS Laboratory of Pathology in 1965, a mere 8 years after joining the division. As the chief, she was known for her evenhanded management of individuals and for her treating everyone with respect. She was known as an excellent mentor, being nurturing yet allowing her trainees and employees to shine on their own. She also recognized talent and nurtured it, especially when that talent was present in a minority individual. Her energy and enthusiasm for science was a major draw for all who worked for her and inspired many to work hard and dedicate themselves to protecting public health. This leadership style led her group to develop safety tests for other viruses and vaccines, such as hepatitis B; work that led to future vaccine development.

In 1972, the DBS was transferred from the NIH to the Food and Drug Administration (FDA), where Ruth was made deputy associate commissioner for science. Immersing herself in the position, she learned all aspects associated with the job, including law, bureaucracy (and how to avoid being snared in it), and administrative finesse; all talents that would serve her well in her future career. After one and a half years, she applied for, interviewed, and in 1974 successfully became, the first female director of an NIH institute, the National Institute of General Medical Sciences (NIGMS). As director, she staffed the institute with highly qualified individuals whom she insured for quality by interviewing personally. She developed a team who could effectively balance smart decision-making, team play, and hard work, thereby increasing morale at the institute, which ultimately strengthened the NIGMS. She was involved in all aspects of the institute, almost to the point of micromanaging. However, by bringing her great attention to detail to an administrative position, she was acutely aware of everything that happened within all levels of the institute.

As director, Ruth understood that basic research does not necessarily rely on a specific outcome but instead results from a growth of knowledge through incremental advances essential for progress. Up until her tenure as director, money for basic research and money for research training, in the form of the NRSA, were separate entities. However, Ruth felt that these two programs should be integrated because the combination of training and research would ensure the long-term support of both. Further, she developed solid relations with politicians on Capitol Hill through her persistence and honesty. She had an uncanny ability to describe difficult concepts in clear terms and to relate the necessity for funding by relating health issues to the personal lives of senators and representatives. As a result of her hard work, the NIGMS budget quadrupled during her tenure.

Soon after starting her position as director, Ruth was asked to chair an NIH committee whose goal was to evaluate the grant peer-review process. She recognized that the process was prone to human error and natural human bias and that the system needed revamping to provide protections from both. Further, she noted the “incestuous” nature of selecting reviewers, in which a reviewer nominated a replacement when they rotated off. This, combined with gender and ethnic biases in the review process resulted in a process that contained few women and few minorities. Her year-long study developed policies that she introduced and are still in place today, changes were made which included members self-nominating for inclusion on a review panel, applicants being allowed to see the critiques from their review, and allowing applicants to argue their case if they believe an unfair or biased critique was given.

Ruth also worked hard to diversify the NIH and examined the programs that targeted underrepresented minorities. She noted that the diversity program at the time, Minority Access to Research Careers (MARC), while being a solid program, didn’t do enough to fully address the issues and only affected a small number of minorities at a handful of institutions. From this realization she developed a new program, the Honors Undergraduate Research Program (HURP), which became a component of MARC. In this program, a series of science honors classes and summer research programs could be implemented at minority institutions to pique interest in science and science careers. Within 10 years of implementing this program, 76% of the program trainees had enrolled in graduate or professional schools. Further, and more generally, Ruth believed that the quality of training depended on its symbiosis with research; and that by investing in training, either to pique an interest in minorities or to support the training of professional school students, the future of science would be strengthened. By being such a strong proponent of training, Ruth was honored in 2002 by having her name added to the NIH’s main training program, which thereafter was known as the Ruth L. Kirschstein NRSA training grants.

In addition to fighting for women and minorities in employment and in education, she also fought to change the way people thought about these populations, particularly women, from a scientific and medical standpoint. She knew that science upheld the fact that women and men were not necessarily the same in terms of clinical responses to treatment or even the health issues they dealt with. However, at the time women, by law, were excluded from clinical trials. Through her work, she became the driving force behind changing the laws about the inclusion of women in clinical studies, raised awareness about the importance of addressing men and women differently in terms of medical and clinical issues, and was instrumental in developing what would become the Office of Research on Women’s Health.

As director of the NIGMS, Ruth oversaw many programs and initiatives that are widely known today. She formed the Recombinant DNA Risk Assessment Committee whose task was to develop guidelines for recombinant DNA research. The results of this committee revolutionized this field producing research that resulted in several Nobel Prizes. She oversaw the development of a database of DNA sequences, which eventually became GenBank, and after years helped develop this program into the National Center for Biotechnology Information (NCBI). She also assisted in working to develop policies that became the Human Genome Project in 1990, a project whose goal was to sequence the entire human genome. She even became a subject in a clinical trial for combination chemotherapy and multimodal treatment when she was diagnosed with inflammatory breast cancer, a treatment that saved her life and is commonly used today.

In 1993, she became the acting director of the NIH while Harold Varmus awaited his approval by Congress. When Varmus took over the reins, Ruth left the NIGMS to become deputy director of the NIH. In this capacity she worked with Varmus, not always agreeing with his opinions, but working hard to make his visions reality and to truly transform the NIH. During this time, too, as science moved fast in many different avenues, Ruth and Varmus worked hard to explain science and its relevance to politicians, the media, and the population at large. Her position as deputy director continued until 2000, when Varmus left the NIH and Ruth once again became the acting director. During her subsequent 2-year tenure she saw the completion of the Human Genome Project, the development of ClinicalTrials.gov, a database where volunteers could search for ongoing medical studies, the establishment of the National Center on Minority Health and Health Disparities, the creation of the National Institute of Biomedical Imaging and Bioengineering, the establishment (in accord with a new law by George W. Bush) of the NIH Guidelines for Research Using Human Embryonic Stem Cells, and supported the creation of the Biomedical Research Infrastructure Network, a program aimed at broadening the geographic distribution of NIH funds. Attesting to her true leadership abilities, she led the NIH through the terrorist attacks of September 11, 2001, and oversaw the transformation of the NIH security in response to that tragedy.

After stepping down as acting director, Ruth stayed on at the NIH serving as senior advisor to the new director, Elias Zerhouni, MD. She continued to work at the NIH until her death at age 83 in 2009, a death that occurred as she wished: with her family by her side, at a place that she loved, the NIH Clinical Center. Ruth L. Kirschstein was a truly amazing person. Her life experiences, growing up the child of Jewish immigrants, both of whom were teachers who instilled an attitude of achieving whatever you put your mind to, along with the attention to social responsibility, created a sense of justice and determination that allowed her to persist through any challenges and accomplish great things. She made an impact on everything she did as a clinician, a scientist, and an administrator; addressing issues of public health, health disparities, inequities in science, and creating many aspects of the NIH that are thriving programs today. Most importantly, she was a teacher, mentor, and advisor to many. Ruth loved to harness peoples’ passions, tapping into those passions to develop unnoticed talents through her mentoring and nurturing. She was a tough mentor, but fair and caring, just like the teacher in school who pushed you to your limits because they saw what you were capable of even when you couldn’t see it for yourself. People were always the main focus for her and she loved the role of teacher. Finally, she believed strongly that providing excellent training to young scientists was the way to ensure the future of scientific endeavors, something she worked tirelessly to...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Dedication
• Acknowledgments
• Preface
• Chapter 1. Ruth L. Kirschstein—The Woman and Her Legacy
• Chapter 2. The People Behind the Curtain—Understanding the Review Process
• Chapter 3. Who Are You?—The Fellowship Applicant
• Chapter 4. Who’s the Boss?—Sponsor, Collaborators, and Consultants
• Chapter 5. Blind Them with Science—The Research Training Plan
• Chapter 6. Last but Not Least: Institutional Environment, Training Potential, and Other Scored Items
• Chapter 7. Details, Details, Details—Nonscored Items, Formatting, and the Cover Letter
• Chapter 8. Now What?—Resubmission
• Appendix. Checklist of Required Items