Time for a change: addressing R&D and commercialization challenges for antibacterials

The antibacterial therapeutic area has been described as the perfect storm. Resistance is increasing to the point that our hospitals encounter patients infected with untreatable pathogens, the overall industry pipeline is described as dry and most multinational pharmaceutical companies have withdrawn from the area. Major contributing factors to the declining antibacterial industry pipeline include scientific challenges, clinical/regulatory hurdles and low return on investment. This paper examines these challenges and proposes approaches to address them. There is a need for a broader scientific agenda to explore new approaches to discover and develop antibacterial agents. Additionally, ideas of how industry and academia could be better integrated will be presented. While promising progress in the regulatory environment has been made, more streamlined regulatory paths are still required and the solutions will lie in global harmonization and clearly defined guidance. Creating the right incentives for antibacterial research and development is critical and a new commercial model for antibacterial agents will be proposed. One key solution to help resolve both the problem of antimicrobial resistance (AMR) and lack of new drug development are rapid, cost-effective, accurate point of care diagnostics that will transform antibacterial prescribing and enable more cost-effective and efficient antibacterial clinical trials. The challenges of AMR are too great for any one group to resolve and success will require leadership and partnerships among academia, industry and governments globally.     

Fragment-based approaches to enzyme inhibition

Fragment-based approaches have provided a new paradigm for small-molecule drug discovery. The methodology is complementary to high-throughput screening approaches, starting from fragments of low molecular complexity and high ligand efficiency, and building up to more potent inhibitors. The approach, which depends heavily on a number of biophysical techniques, is now being taken up by more groups in both industry and academia. This article describes key aspects of the process and highlights recent developments and applications.     

Enhancing ties between academia and industry to improve health

Concerns about conflicts of interest have driven a wedge between academia and the pharmaceutical and devices industries. Although elevated concern for bias is justified, particularly when academics may affect drug sales, partnerships between industry and academia are essential to achieve the full promise of health improvement from the public investment in biomedical research. New models for such partnerships are developing and should be encouraged.     

Recent advances in the discovery of organometallic catalysts using high-throughput screening assays

Combinatorial techniques were developed initially to accelerate the identification of molecules with biological activity. The successes of these techniques inspired the design of high-throughput methods to assist in the discovery of new catalysts. Over the past year, many groups in academia and industry have utilized high-throughput screening assays to reduce the time required to identify catalysts for asymmetric processes, cross-coupling reactions and other metal-catalyzed transformations. The continued success of combinatorial techniques in organometallic chemistry should propagate the development of new and improved methods to facilitate catalyst discovery.     

Regulating innovative crop technologies in Canada: the case of regulating genetically modified crops

The advent of genetically modified crops in the late 1980s triggered a regulatory response to the relatively new field of plant genetic engineering. Over a 7-year period, a new regulatory framework was created, based on scientific principles that focused on risk mitigation. The process was transparent and deliberately sought the input of those involved in crop development from non-governmental organizations, industry, academia and federal research laboratories. The resulting regulations have now been in place for over a decade, and the resilience of the risk-mitigating regulations is evident as there has been no documented case of damage to either environment or human health.     

The need for academic generalists

Academia should be willing to shoulder some of the responsibility for the current dearth of new therapeutic drugs. Our research funding is predicated on the assumption that it will bring value to society, but our emphasis on scientific specialization hinders our ability to add value when a broader vision is required. A solution is the creation of an academy of science generalists motivated to bring together clinical and basic scientists, academia and the private sector, government legislators and industry. A small investment in academic generalists could yield benefits far beyond its modest cost.     

Journal Impact Factor Shapes Scientists’ Reward Signal in the Prospect of Publication

The incentive structure of a scientist’s life is increasingly mimicking economic principles. While intensely criticized, the journal impact factor (JIF) has taken a role as the new currency for scientists. Successful goal-directed behavior in academia thus requires knowledge about the JIF. Using functional neuroimaging we examined how the JIF, as a powerful incentive in academia, has shaped the behavior of scientists and the reward signal in the striatum. We demonstrate that the reward signal in the nucleus accumbens increases with higher JIF during the anticipation of a publication and found a positive correlation with the personal publication record (pJIF) supporting the notion that scientists have incorporated the predominant reward principle of the scientific community in their reward system. The implications of this behavioral adaptation within the ecological niche of the scientist’s habitat remain unknown, but may also have effects which were not intended by the community.     

Promising antifungal agents: A minireview

In the recent past, prevalence of life threatening fungal diseases have increased rapidly in immune-compromised cases such as acquired immunodeficiency syndrome (AIDS), cancer, organ transplant etc. Side by side, the appearance of drug resistance to the presently available antifungal therapeutics is on a rapid rise. It has become a top priority for the academia and pharmaceutical industries to develop new antifungal agents able to combat this resistance, and at the same time, possess potential broad spectrum of activity and minimum toxicity. An understanding of the pharmacological interactions between antifungal agents and their targets offers opportunities for design of new therapeutics. This review discusses the various methodology of drug design, structure activity relationships (SARs), and mode of action of variety of new antifungal agents.     

Leaks in the pipeline: separating demographic inertia from ongoing gender differences in academia

Identification of the causes underlying the under-representation of women and minorities in academia is a source of ongoing concern and controversy. This is a critical issue in ensuring the openness and diversity of academia; yet differences in personal experiences and interpretations have mired it in controversy. We construct a simple model of the academic career that can be used to identify general trends, and separate the demographic effects of historical differences from ongoing biological or cultural gender differences. We apply the model to data on academics collected by the National Science Foundation (USA) over the past three decades, across all of science and engineering, and within six disciplines (agricultural and biological sciences, engineering, mathematics and computer sciences, physical sciences, psychology, and social sciences). We show that the hiring and retention of women in academia have been affected by both demographic inertia and gender differences, but that the relative influence of gender differences appears to be dwindling for most disciplines and career transitions. Our model enables us to identify the two key non-structural bottlenecks restricting female participation in academia: choice of undergraduate major and application to faculty positions. These transitions are those in greatest need of detailed study and policy development.     

Small and lethal: searching for new antibacterial compounds with novel modes of action.

The discovery of drugs used to combat infectious diseases is in the process of constant change to address the ever-worsening problem of antibiotic resistance in pathogens and a lack of recent success in discovering new antibacterial drugs. In the past 2 decades, research in both academia and industry has made use of molecular biology, genetics, and comparative genomics, which has led to the development of key technologies for the discovery of novel antibacterial agents. Genome-scale efforts have led to the identification of numerous molecular targets. Chemical diversity from synthetic combinatorial libraries and natural products is being used to screen for new molecules. A wide variety of approaches are being used in the search for novel antibiotics, and these can be categorized as being either biochemically focused or cell based. The over-riding goal of all methods in use today is to discover new chemical matter with novel mechanisms of action against drug-resistant pathogens.     

The Innovative Vector Control Consortium: improved control of mosquito-borne diseases

Few new insecticides have been produced for control of disease vectors for public health in developing countries over the past three decades, owing to market constraints, and the available insecticides are often poorly deployed. The Innovative Vector Control Consortium will address these market failures by developing a portfolio of chemical and technological tools that will be directly and immediately accessible to populations in the developing world. The Bill and Melinda Gates Foundation has supported this new initiative to enable industry and academia to change the vector control paradigm for malaria and dengue and to ensure that vector control, alongside drugs, case management and vaccines, can be better used to reduce disease.     

The role of modern biology and medicine in drug development in academia and industry

This symposium addresses careers in drug development in industry; the performance of translational research by academia, industry, and both; and numerous factors pertinent to alliances essential to drug discovery and development. Drug development is a complex process that regularly involves effective collaborations between academic and physician scientists and industry. There are specific occupational factors affecting recruitment of scientists and physicians in drug development programs in industry; ideal backgrounds for successful applicants for positions in industry in drug development; ethical and regulatory considerations particularly germane to the performance of scientists and physicians in drug development programs in industry and at universities; and particular gratifications available to scientists in industry working on drug development. Both similarities and differences characterize the performance of translational research in industry compared with academia. In industry, logistic, operational, and scientific oversight is complex, especially because it often involves relationships with clinical enterprises outside of the corporation. The process is long and arduous from formulation of a good idea in discovery to acceptance of a novel drug in the marketplace. Collaborations and partnerships by industry often involving academia and confrontation of multiple issues are pivotal.     

Whole-cell living biosensors—are they ready for environmental application?

Since the development of the first whole-cell living biosensor or bioreporter about 15 years ago, construction and testing of new genetically modified microorganisms for environmental sensing and reporting has proceeded at an ever increasing rate. One and a half decades appear as a reasonable time span for a new technology to reach the maturity needed for application and commercial success. It seems, however, that the research into cellular biosensors is still mostly in a proof-of-principle or demonstration phase and not close to extensive or commercial use outside of academia. In this review, we consider the motivations for bioreporter developments and discuss the suitability of extant bioreporters for the proposed applications to stimulate complementary research and to help researchers to develop realistic objectives. This includes the identification of some popular misconceptions about the qualities and shortcomings of bioreporters.     

Mode of action of adjuvants: Implications for vaccine safety and design

For decades, the search for new vaccine adjuvants has been largely empirical. A series of new adjuvants and related formulations are now emerging that are acting through identified immunological mechanisms. Understanding adjuvant mechanism of action is crucial for vaccine design, since this allows for directing immune responses towards efficacious disease-specific effector mechanisms and appropriate memory. It is also of great importance to build new paradigms for assessing adjuvant safety at development stages and at regulatory level. This report reflects the conclusions of a group of scientists from academia, regulatory agencies and industry who attended a conference, organized by the International Association for Biologicals (IABS), on the mode of action of adjuvants on 29–30 April 2010 in Bethesda, Maryland, USA, particularly focusing on how understanding adjuvants mode of action can impact on the assessment of vaccine safety and help to develop target-specific vaccines. More information on the conference output can be found on the IABS website, http://www.iabs.org/.     

Drug discovery and development for neglected parasitic diseases

Diseases caused by tropical parasites affect hundreds of millions of people worldwide but have been largely neglected for drug development because they affect poor people in poor regions of the world. Most of the current drugs used to treat these diseases are decades old and have many limitations, including the emergence of drug resistance. This review will summarize efforts to reinvigorate the drug development pipeline for these diseases, which is driven in large part by support from major philanthropies. The organisms responsible for these diseases have a fascinating biology, and many potential biochemical targets are now apparent. These neglected diseases present unique challenges to drug development that are being addressed by new consortia of scientists from academia and industry.     

A sponsorship action plan for increasing diversity in STEMM

There are numerous structural and cultural barriers to the progression of women and marginalized groups to leadership in academia, especially in Science, Technology, Engineering, Mathematics and Medicine (STEMM). A range of interventions have been described to address this inequity, with varying success. Here, we suggest that sponsorship could be one effective intervention and propose an institutional action plan to implement a sponsorship program in academia. We outline why sponsorship could be an effective strategy, especially if implemented through a deliberate program by an institution. We then detail the three components of an action plan to be considered in implementation: the elements of the program, the activities that sponsorship in academia likely encompasses, and the selection of sponsors and protégés. The plan could also be enacted by academic leadership in the absence of an institutional program and could serve as a guide to individuals in academia aspiring to address diversity and inclusion in STEMM.     

Putting the Predictive Toxicology Challenge into perspective: reflections on the results

MOTIVATION: Chemical carcinogenicity is of primary interest, because it drives much of the current regulatory actions regarding new and existing chemicals, and its experimental determination involves time-consuming and expensive animal testing. Both academia and private companies are actively trying to develop SAR and QSAR models. This paper reviews the new Predictive Toxicology Challenge (PTC) results, by putting them into the context of previous attempts. RESULTS: A marked dependency of the prediction ability of the different algorithms on the training sets was observed, pointing to a still insufficient coverage of the chemical carcinogens 'universe'. A theoretical treatment of the possible developments of the Artificial Intelligence approaches is sketched.     

Knowledge networks in the age of the Semantic Web

The Web has become the major medium for various communities to share their knowledge. To this end, it provides an optimal environment for knowledge networks. The web offers global connectivity that is virtually instantaneous, and whose resources and documents can easily be indexed for easy searching. In the coupled realms of biomedical research and healthcare, this has become especially important where today many thousands of communities already exist that connect across academia, hospitals and industry. These communities also rely on several forms of knowledge assets, including publications, experimental data, domain-specific vocabularies and policies. Web-based communities will be one of the earlier beneficiaries of the emerging Semantic Web. With the new standards and technologies of the Semantic Web, effective utilization of knowledge networks will expand profoundly, fostering new levels of innovation and knowledge.     

Get that next job—how to break out of the postdoc trap

In the past, the majority of graduate students and postdoctoral researchers were focused on careers in academia. Times have changed, and many are now considering careers outside of academia and are aware of numerous exciting career opportunities in industry and nonprofit and government organizations. However, although it is easy to find resources about academic careers, the same cannot be said for positions outside the ivory tower. Here, on the basis of my experience as a scientist and as someone who works with graduate students and postdocs to help them enter nonacademic career paths, I provide a perspective on career development and how to find a job.     

Group sequential and adaptive designs - a review of basic concepts and points of discussion

In recent times, group sequential and adaptive designs for clinical trials have attracted great attention from industry, academia and regulatory authorities. These designs allow analyses on accumulating data - as opposed to classical, "fixed-sample" statistics. The rapid development of a great variety of statistical procedures is accompanied by a lively debate on their potential merits and shortcomings. The purpose of this review article is to ease orientation in both respects. First, we provide a concise overview of the essential technical concepts, with special emphasis on their interrelationships. Second, we give a structured review of the current controversial discussion on practical issues, opportunities and challenges of these new designs.