Congress passed the Genetic Information Nondiscrimination Act of 2008 (GINA) in order to remove a perceived barrier to clinical genetic testing. By banning health insurance companies and employers from discriminating against an individual based on his or her genetic information, legislators hoped that patients would be encouraged to seek genetic testing that could improve health outcomes and provide opportunities for preventive measures. Their explicit legislative goal was to fully protect the public from discrimination and allay their concerns about the potential for discrimination, thereby allowing individuals to take advantage of genetic testing, technologies, research, and new therapies.

However, GINA left a number of issues unresolved, most notably failing to define the concept of disease manifestation. GINA was structured such that it only provides protection against misuse of genetic information up until the point when an individual's disease has manifested. It protects an individual with a genetic predisposition for a disease, but not an individual actively suffering from that disease.

Criticisms of the traditional clinical research pathway and its extensive oversight often focus on proposals for deregulation or assert that as in clinical treatment, clinical research should always offer benefit to patient-subjects. Proponents of medical innovation take a different, middle path, arguing that innovation is distinguishable from both research and treatment. This article considers this third pathway by examining stem cell-based innovation.

Stem cell-based medical innovation is one pathway toward clinical translation. In fact, such an approach was taken in developing umbilical cord blood transplantation, which is now widely viewed as a safe and effective means for treating a range of malignant and non-malignant conditions. While the Guidelines for the Clinical Translation of Stem Cells created by the International Society for Clinical Research (ISSCR) provide an approach to clinical translation that involves “responsible innovation” as an alternative to clinical research, there are at least four sets of unanswered questions regarding the use of an innovation pathway in this context that warrant careful attention.

Pediatric participation in non-therapeutic research that poses greater than minimal risk has been the subject of considerable thought-provoking debate in the research ethics literature. While the need for more pediatric research has been called morally imperative, and concerted efforts have been made to increase pediatric medical research, the importance of protecting children from undue research risks remains paramount.

United States research regulations are derived largely from the deliberations and report of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The authors of this report specifically designated children as a vulnerable population and suggested additional protections, most of which became U.S. law. One of the more contested sets of regulations surrounds non-therapeutic research, e.g., research that does not offer the potential for direct benefit to participants. Federal regulations allow local Institutional Review Boards (IRBs) to approve non-therapeutic research posing a minor increase above minimal risk when it involves children who have the disease or medical condition that the research addresses (Table 1).

There are not many public health issues where views are as extremely polarized as those concerning vaccination policies. Ever since its Fast Track approval by the U.S. Food and Drug Administration (FDA) in 2006, Merck's human papilloma virus (HPV) vaccine Gardasil has been sparking controversy. Initially, the criticism has been focused at Merck, due to their overly aggressive marketing strategies and lobbying campaigns. According to a 2007 editorial in Nature Biotechnology, Surrounded by a chorus of disapproval, Merck cracked. As Nature Biotechnology went to press, the company announced a cessation of all efforts to lobby for US state laws requiring compulsory vaccination. Subsequently, questions have been raised whether it was appropriate for vaccine manufacturers to partake in public health policies when their conflicts of interests were so obvious. Some of their advertising campaign slogans, such as cervical cancer kills x women per year and your daughter could become one less life affected by cervical cancer, seemed more designed to promote fear rather than evidence-based decision making about the potential benefits of the vaccine versus any risks.

Institutional Review Board (IRB) decisions hinge on the availability and interpretation of information. This is demonstrated by the following well-known historical example. In 2001, 24-year-old Ellen Roche died from respiratory distress and organ failure as a result of her participation in a study at Johns Hopkins Asthma and Allergy Center. The non-therapeutic physiological study, “Mechanisms of Deep Inspiration-Induced Airway Relaxation,” was designed to examine airway hyperresponsiveness in healthy individuals in order to better understand the pathophysiology of asthma. Participants inhaled hexamethonium, a chemical ganglionic blocker that was not FDA-approved for use as specified in the experimental protocol. Risks of inhaling hexamethonium, including lung damage, had been reported in the 1950s and ‘60s. An investigation conducted after Roche's death determined that the study's principal investigator had failed to adequately search the medical literature; the protocol submitted for IRB review cited articles indexed in online literature databases that went back only as far as the 1970s.

The physician-researcher conflict of interest, a long-standing and widely recognized ethical challenge of clinical research, has thus far eluded satisfactory solution. The conflict is fairly straightforward. Medical research and medical therapy are distinct pursuits; the former is aimed at producing generalizable knowledge for the benefit of future patients, whereas the latter is aimed at addressing the individualized medical needs of a particular patient. When the physician-researcher combines these pursuits, he or she serves two masters and cannot — no matter how well-intentioned — avoid the risk of compromising the duties owed in one of the professional roles assumed. Because of the necessary rigidity of a research protocol, the more demanding of the two masters is frequently the research.

The problem of the physician-researcher conflict has been evident since the first attempts to regulate human research in the United States. Otto E. Guttentag, a physician at the University of California School of Medicine in San Francisco, addressed the conflict in a 1953 Science magazine article.

From the earliest days of the Human Genome Project, the holy grail of genomics was the ability to perform whole-genome sequencing quickly, accurately, and relatively inexpensively so that the benefits of genomics would be widely available in clinical settings. Although the mythical $1,000 genome sequence seemed elusive for many years, next-generation sequencing technologies and other recent advances clearly indicate that inexpensive whole-genome sequencing is at hand.

Whole-genome sequencing has demonstrable value in elucidating the genetic etiology of rare disorders, in identifying atypical variants in common diseases, in determining pharmacogenomically appropriate drugs and dosages, in performing tumor genome sequencing, and in aiding other clinical applications for the diagnosis and treatment of individuals who are symptomatic or whose family health history places them at substantial risk. Undoubtedly, the clinical applications of wholegenome sequencing will increase in the future.

Promoting and protecting the public's health in the United States and abroad are intricately tied to laws and policies. Laws provide support for public health measures, authorize specific actions among public and private actors, and empower public health officials. Laws can also inhibit or restrict efforts designed to improve communal health through protections for individual rights or structural principles of government. Advancing the health of populations through law is complex and subject to constant tradeoffs. This column seeks to explore the role of law in the interests of public health through scholarly and applied assessments across a spectrum of key issues. The first of these assessments focuses on a critical topic in emergency legal preparedness.

Deception, cheating, and loopholes within the IRB approval process have received significant attention in the past several years. Surveys of clinical researchers indicate common deception ranging from omitting information to outright lying, and controversy surrounding the FDA's decision not to ban “IRB shopping” (the practice of submitting protocols to multiple IRBs until one is found that will approve the protocol) has raised legitimate concerns about the integrity of the IRB process. One author has described a multicenter trial as being withdrawn from consideration at one institution when rejection was imminent, in order to avoid informing other IRBs reviewing the protocol of the study's rejection (a requirement under the federal regulations for emergency research with an exception from informed consent). This practice and IRB shopping seem at odds with the spirit, if not the “letter,” of the regulations. While at first blush these practices seem to cast aspersions on the integrity of clinical researchers, the moral issues raised go deeper than the ethics of cheating.

In the last several years, Brazil has gained international attention as an emerging BRIC economy, was awarded the 2014 World Cup and 2016 Olympics, and elected its first female president. This has led many to declare that Brazil is emerging as a potential world power for the 21st century. In addition to improving its international stature, in the last several decades Brazil has also significantly improved the availability and quality of health care within the country. Despite these gains, however, Brazil still suffers from poor maternal health. In fact, Brazil's Maternal Mortality Ratio is five to ten times higher than the rates in high-income countries. Last year, these conditions lead the United Nations Committee on the Elimination of Discrimination against Women to issue a decision declaring that Brazil was violating its international obligations to provide pregnant women with adequate health care, and to call for a reduction in preventable maternal deaths. It is against this backdrop that Brazil enacted a new law last December, Provisional Measure 557 (MP 557), to require pregnant women to register with the state.

A number of unique problems plague human research protection efforts at United States (US) State and Territorial Departments of Health (DOHs). The first problem is related to the number of Institutional Review Boards (IRBs) operated by and Federalwide Assurances (FWAs) held by DOHs. The lack of these two essential regulatory human research protection program mechanisms points to a possible inadequacy of infrastructure at DOHs for protecting human subjects. The second and third problems are related to the use and interpretation of research protection laws and regulations at DOHs. Parsing public health activities into research or practice (1) can be vexing and (2) likely produces variability in (a) how individual DOHs make the determination between research and practice and (b) the outcomes of such decisions for the same or similar projects. A related problem is that DOH or Institutional Review Board (IRB) officials might misclassify public health practice activities as research (and vice versa), which can have costly, adverse consequences.

In much the same way that genomic technologies are changing the complexion of biomedical research, the issues they generate are changing the agenda of IRBs and research ethics. Many of the biggest challenges facing traditional research ethics today — privacy and confidentiality of research subjects; ownership, control, and sharing of research data; return of results and incidental findings; the relevance of group interests and harms; the scope of informed consent; and the relative importance of the therapeutic misconception — have become important policy issues over the last 20 years because of the ways they have been magnified by genomic research efforts. Research that examines the ethical, legal, and social implications (ELSI) of human genomics research has become a burgeoning international field of scholarship over the last 20 years, thanks in part to its support first by the genome research funding bodies in the U.S. and then by national science agencies in other countries.

Access to clear and concise medication information is essential to support safe and effective use of prescription drugs. Patient misunderstanding of medication information is a common reason for non-adherence to medication regimens and a leading cause of outpatient medication errors and adverse drug events in the U.S. Medication errors are the most common source of risk to patient safety, leading to poor health outcomes, hospitalizations, and deaths. Over half a million adverse drug events occur in the outpatient setting each year at a cost of approximately $1 billion annually.

Nearly half of adults in the U.S. experience difficulty understanding and acting upon health information. Even individuals with high levels of general literacy may find medication information difficult to understand or use. The risk of misunderstanding medication information is compounded for patients with limited English proficiency (LEP) who may not have access to this information in their own language.

Major advances, ground-breaking scholarship, and new programs in public health law over the past several decades have helped define and reform the field. The extent to which public health law is established as a distinct topic for graduate academic study, however, is uncertain. In the early 1990s, the numbers of academics whose work focused largely on public health law were few. Only a handful of schools of law, public health, and medicine regularly offered core courses in public health law (although many graduate courses in health law, bio-ethics, or public health policy featured select public health law topics). Collectively, these courses laid a strong foundation of instruction in public health law. Still, questions remain as to whether public health law has progressed as a topic of academic pursuit in American graduate institutions. Who is teaching core courses in public health law? Where are these courses taught? How are they designed and what specific topics are covered?

Increasingly, genomic analysis is being utilized to diagnose children with developmental delay or dysmorphic facial features suggestive of a congenital disorder. Genetic testing has rapidly evolved, and the genome-wide tests that we use today are significantly different from the more targeted single-gene tests of the last decade. Chromosomal microarray analysis (CMA) is now a first line test for children with multiple birth defects, children with intellectual impairment (including autism), and children with an unusual constellation of symptoms that do not fit with a known disease. There are three types of CMA that are currently clinically available. CMA by oligonucleotide array-based comparative genomic hybridization (aCGH) compares the hybridization signal from the patient's DNA to that of a reference DNA sample for each oligonucleotide on the array. Depending on the specific array, this can range from tens of thousands to hundreds of thousands of oligonucleotides.