Commentary

Successful translation of modern molecular immunology into effective cancer immunotherapy is threatened by regulatory barriers and challenges to the development of novel agents and combinatorial strategies through effective public-private partnerships. For its promise to be fully realized, both the National Cancer Institute and Food and Drug Administration must take active steps to help academic investigators and companies jointly navigate the pathways from laboratory to clinic.

Research groups worldwide are trying to make immunogens intended to elicit neutralizing antibody responses as part of a prophylactic vaccine to counter the spread of HIV-1. The relative merits of different designs can only be gauged properly through comparative studies, and particularly by evaluating human or animal antisera under identical, or comparable, conditions. Hence there is a need for assay standardization and for the creation of a centralized testing facility that could distribute consensus protocols and reagents.

Biobanks will have a crucial role in the identification of genes associated with disease — a prerequisite to designing adequate diagnostic and therapeutic tools. To maximize their impact and chances of success, collaboration at a global scale is highly desirable.

The question “When are research risks reasonable in relation to anticipated benefits?” is at the heart of disputes in the ethics of clinical research. Institutional review boards are often criticized for inconsistent decision-making, a problem that is compounded by a number of contemporary controversies, including the ethics of research involving placebo controls, developing countries, incapable adults and emergency rooms. If this pressing ethical question is to be addressed in a principled way, then a systematic approach to the ethics of risk in research is required. Component analysis provides such a systematic approach.

Obese people, who are already subject to adverse health effects, are additionally victimized by a social stigma predicated on the Hippocratic nostrum that weight can be controlled by 'deciding' to eat less and exercise more. This simplistic notion is at odds with substantial scientific evidence illuminating a precise and powerful biologic system that maintains body weight within a relatively narrow range. Voluntary efforts to reduce weight are resisted by potent compensatory biologic responses. This article will review some of this evidence, together with promising avenues of research. Further progress in understanding and treating obesity will come not from repetition of anachronistic preconceptions but rather from the rigorous scientific approach that has driven advances in so many other areas of medicine.

Human/nonhuman stem cell chimeras will be increasingly applied to study human cells in developing nonhuman animals. Such experiments raise a number of issues that may create further controversy in the stem cell field. Here we outline the scientific value and ethical ramifications of such studies, and suggest how such experiments may be conducted ethically.

Several lines of evidence indicate that development of an effective vaccine for HIV-1 is going to be, at best, extremely difficult. The inability to solve fundamental scientific questions is the root cause for why a successful vaccine is not currently within our grasp. A renewed, organized, focused effort is needed to overcome these scientific obstacles.

Using stem cells to generate new neurons and replace those lost in diseases such as Parkinson and amyotrophic lateral sclerosis would be a major breakthrough, but significant hurdles remain before this goal can be realized. Instead, a more practical short-term approach may be to use stem cells to protect neurons dying in these diseases.

Scaling up access to antiretroviral drugs (ARVs) for HIV-infected adults and children in developing countries can no longer be refused for medical or economic reasons, or on the grounds of inequality, lack of infrastructure, risk of viral resistance or alternative priorities. Access to ARVs is an appropriate, rational and cost-effective investment choice in developing countries.

Between the first analysis of patient samples in early 1983 and the determination of the sequence of HIV-1 in 1985, a vast amount of data was accumulated on HIV through the integrated efforts of clinicians, virologists, immunologists, molecular biologists and epidemiologists. These early years of HIV research quickly led to strategies for the diagnosis, monitoring and treatment of HIV/AIDs

Although the future of HIV science is uncertain, we need to reappraise HIV diversity, pathogenesis and immunity. The AIDS pandemic threatens the success of existing vaccine programs and may accelerate the emergence of new infectious diseases.

From the identification of HIV as the agent that causes AIDS, to the development of effective antiretroviral drugs, the scientific achievements in HIV research in the past 20 years have been formidable. Some of the other important areas of accomplishment include the development of blood tests for HIV and increased knowledge of the molecular virology, epidemiology and pathogenesis of this virus.

S-nitroso-hemoglobin (SNOHb) has been proposed to regulate blood flow and tissue oxygenation through allosterically controlled binding and delivery of nitric oxide (NO) and oxygen in the vasculature. This precept and the experiments that test it have provoked both ardent support and expanding dissent. An alternative view suggests that a physiologically tightly regulated balance of NO scavenging by hemoglobin and NO production by endothelial cells determines NO bioavailability.

At the crossroads of academia and industry, translational research provides the vehicle for the application of medical discoveries and developments. A productive and expanded relationship between these two sectors is essential for the continued success in translating basic research findings to the clinic.

Chromosomal translocations occur in leukemias, lymphomas, sarcomas and some epithelial tumors and some generate unique fusion proteins. These translocation products may provide tumor-specific targets for the development of new therapeutic strategies tailored to a malignant cell.