On 23 April 2008, the US Government Accountability Office, or GAO, released a report titled, “Abstinence Education: Assessing the Accuracy and Effectiveness of Federally Funded Programs,” hereafter “Abstinence Education,” in which it investigated the scientific accuracy and effectiveness of abstinence-only education programs sanctioned by individual states and the US Department of Health and Human Services, or HHS. GAO is a government agency whose role is to examine the use of public funds, evaluate federal programs and activities, and provide nonpartisan support to the US Congress. In “Abstinence Education,” GAO found that as of August 2006, a variety of factors in such programs, such as inaccurate medical information, contributed to overall conclusions that abstinence-until-marriage programs were unsuccessful at reducing the rates of adolescent pregnancy. In “Abstinence Education,” GAO recommends that HHS implement procedures to better assure the accuracy of educational materials used in abstinence programs and to set standards that measure the effectiveness of those programs.

Henrietta Lacks, born Loretta Pleasant, had terminal cervical cancer in 1951, and was diagnosed at The Johns Hopkins University in Baltimore, Maryland, where researchers collected and stored her cancer cells. Those cells went on to become the first immortal human cell line, which the researchers named HeLa. An immortal cell line is an atypical cluster of cells that continuously multiply on their own outside of the organism from which they came, often due to a mutation. Lacks’s cancer cells enabled scientists to study human cells outside of the human body, though that was controversial since she did not voluntarily donate her cells for such research. Science writer Rebecca Skloot chronicled Lacks’s life in her book, The Immortal Life of Henrietta Lacks, which became a movie in 2017. Lacks’s HeLa cell line has contributed to numerous biomedical research advancements and discoveries and her story has prompted legal and ethical debates over the rights that an individual has to their genetic material and tissue.

The HeLa cell line was the first immortal human cell line that George Otto Gey, Margaret Gey, and Mary Kucibek first isolated from Henrietta Lacks and developed at The Johns Hopkins Hospital in Baltimore, Maryland, in 1951. An immortal human cell line is a cluster of cells that continuously multiply on their own outside of the human from which they originated. Scientists use immortal human cell lines in their research to investigate how cells function in humans. Though the HeLa cell line has contributed to many advancements in biomedical research since the twentieth century, its usage in medical research has been controversial because Lacks did not consent to having her cells used for such purposes. As of 2020, scientists continue to use the HeLa cell line for numerous scientific advancements, such as the development of vaccines and the identification of many underlying disease mechanisms.

The 1981 Adolescent Family Life Act, or AFLA, is a US federal law that provides federal funding to public and nonprofit private organizations to counsel adolescents to abstain from sex until marriage. AFLA was included under the Omnibus Reconciliation Act of 1981, which the US Congress signed into law that same year. Through the AFLA, the US Department of Health and Human Services, or HHS, funded a variety of sex education programs for adolescents to address the social and economic ramifications associated with pregnancy and childbirth among unmarried adolescents. AFLA received several criticisms for directly emphasizing and funding abstinence-only education programs from religious organizations. However, when US citizen Chan Kendrick brought the case Bowen v. Kendrick before the Supreme Court in 1988, the Court upheld that AFLA was constitutional. Although numerous evaluations have shown minimal scientific evidence supporting abstinence-only education, as of 2020, the federal government still provides funding for such programs through AFLA.

Published in 2002, prostate cancer researcher John R. Masters authored a review article HeLa Cells 50 Years On: The Good, The Bad, and The Ugly that described the historical and contemporary context of the HeLa cell line in research in Nature Reviews Cancer. The HeLa cell line was one of the first documented immortal cell lines, isolated from cervical cancer patient Henrietta Lacks in 1951 at The Johns Hopkins Hospital in Baltimore, Maryland. An immortal cell line is a cluster of cells that continuously multiply on their own outside of the original host. Though the HeLa cell line has contributed to many biomedical research advancements such as the polio vaccine, its usage in research has been controversial for many reasons, including that Lacks was a Black woman who did not knowingly donate her cells to science. In the article “HeLa Cells 50 Years On: The Good, The Bad, and The Ugly,” Masters describes that, despite the benefits of the HeLa cell line, it has caused significant negative impacts on research due to its propensity to contaminate other cell lines, which can potentially invalidate research findings.

On 29 June 1988, in Bowen v. Kendrick, the US Supreme Court ruled in a five-to-four decision that the 1981 Adolescent Family Life Act, or AFLA, was constitutional. Under AFLA, the US government could distribute federal funding for abstinence-only sexual education programs, oftentimes given to groups with religious affiliations. As a federal taxpayer, Chan Kendrick challenged the constitutionality of AFLA, claiming it violated the separation of church and state. The Supreme Court found that although AFLA funded programs that aligned with certain religious ideologies, it was constitutional because it did not encourage government involvement in religion, and it held a valid secular purpose in seeking to prevent adolescent pregnancy and premarital sexual relations. By upholding AFLA, Bowen v. Kendrick enabled the US government to continue funding abstinence-only education, which researchers have found to be ineffective.

In “Explaining Recent Declines in Adolescent Pregnancy in the United States: The Contribution of Abstinence and Improved Contraceptive Use,” hereafter “Explaining Recent Declines,” researchers John S. Santelli, Laura Duberstein Lindberg, Lawrence B. Finer, and Susheela Singh discuss what led to the major decline in US adolescent pregnancy rates from 1995 to 2002. Working with the Guttmacher Institute, a reproductive health research organization, they found that the decline in US adolescent pregnancy rates between 1995 and 2002 was primarily due to improved contraceptive use. They published their article in 2007 after the US government had increased funding for abstinence-only education between 1998 and 2007. “Explaining Recent Declines” challenged US policies by asserting that there was minimal evidence to support abstinence-only sex education as the primary strategy to prevent adolescent pregnancy.

On 9 July 1990, in Moore v. Regents of the University of California, the Supreme Court of California ruled in a four-to-three decision that individuals do not have rights to a share in profits earned from research performed on their bodily materials. In its decision, the Supreme Court of California ruled that cancer patient John L. Moore did not have personal property rights to samples or fluids that his physicians took from his body for research purposes. Moore created the precedent in California that although physicians are required to disclose their research interests to their patients, patients do not have property-related claims to any samples that their physicians take from their body. The Supreme Court of California’s decision in Moore v. Regents of the University of California enabled physicians and researchers to retain legal ownership on samples taken from their patients’ bodies so that they can conduct what the court describes as socially important medical research, such as work on reproductive cancers or developmental disorders.

In cancer, various genetic and epigenetic alterations cause cancer cells to hyperproliferate and to bypass the survival and migration mechanisms that typically regulate healthy cells. The focal adhesion kinase (FAK) gene produces FAK, a protein that has been implicated in tumor progression in various cancers. Compared with normal tissue counterparts, FAK is overexpressed in many cancers. FAK is therefore a promising cancer drug target due to its demonstrated role in cancer invasion and metastasis and inhibition of FAK is important to achieve an optimal tumor response. Small molecule FAK inhibitors have been shown to decrease tumor growth and metastasis in several preclinical trials. However, these inhibitors focus narrowly on the enzymatic portion of FAK and neglect its scaffolding function, leaving FAK’s scaffolding of oncogenic drivers intact. Paxillin, a major focal adhesion-associated protein, binds to FAK, enabling it to localize to focal adhesions, and this is essential for FAK’s activation and function. Therefore, disrupting the protein-protein interaction between FAK and paxillin has been hypothesized to prevent tumor progression. The binding of FAK to paxillin at its focal adhesion targeting (FAT) domain is mediated by two highly conserved leucine-rich sequences, the leucine-aspartic acid (LD) motifs LD2 and LD4. The purpose of this project was to develop novel stapled LD2 peptide analogs that target the protein-protein interaction of FAT to LD2. Peptide stapling was performed to enhance the pharmacological performance of the LD2 peptide analogs. Based on the native LD2 peptide sequence, stapled LD2 peptide analogs were developed with the intent to improve efficacy of cell permeability, while maintaining or improving FAK binding. The LD2 peptide analogs were characterized via surface plasmon resonance, fluorescence polarization, immunofluorescence, and circular dichroism spectroscopy. Successful LD2 stapled peptide analogs can be therapeutically relevant inhibitors of the FAT-LD2 protein-protein interaction in cancer and have the potential for greater efficacy in FAK inhibition, proteolytic resistance, and cell permeability, which is key in preventing tumor progression in cancer.