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.     

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.     

Exploring the therapeutic potential of staphylococcal phage formulations: Current challenges and applications in phage therapy

Unconstrained consumption of antibiotics throughout the expanse of the 21st century has resulted in increased antimicrobial resistance (AMR) among bacterial pathogens, a transpiring predicament affecting the public healthcare sector. The upsurge of multidrug-resistant pathogens, including Staphylococcus aureus, synchronously with the breakdown of the conventional antibiotic pipeline has led to the exploration of alternate strategies. Phage therapy applications have thus gained immense prominence among the scientific community to conquer this notorious pathogen associated with wide-ranging clinical manifestations, especially in immunosuppressed individuals. In this direction, a plethora of phage formulations like topical solutions, medicated dressings impregnated with phages, liposomal entrapments, etc., have been considered as an effective and upcoming strategy. Owing to the synergistic effect of phages with other antibacterial agents, they can be easily exploited for biomedical application. This review primarily focuses on the therapeutic implications of S. aureus phages in the biotechnological and medical arena. Through this review article, we have also discussed the current status and the incurring challenges in phage therapy.     

Accelerating the development of innovative cellular therapy products for the treatment of cancer

The field of cell therapy is rapidly emerging as a priority area for oncology research and drug development. Currently, two chimeric antigen receptor T-cell therapies are approved by the US Food and Drug Administration and other agencies worldwide for two types of hematologic cancers. To facilitate the development of these therapies for patients with life-threatening cancers with limited or no therapeutic options, science- and risk-based approaches will be critical to mitigating and balancing any potential risk associated with either early clinical research or more flexible manufacturing paradigms. Friends of Cancer Research and the Parker Institute for Cancer Immunotherapy convened an expert group of stakeholders to develop specific strategies and proposals for regulatory opportunities to accelerate the development of cell therapies as promising new therapeutics. This meeting took place in Washington, DC on May 17, 2019. As academia and industry expand research efforts and cellular product development pipelines, this report summarizes opportunities to accelerate entry into the clinic for exploratory studies and optimization of cell products through manufacturing improvements for these promising new therapies.     

Digital biology: an emerging and promising discipline

This article examines the role of computation and quantitative methods in modern biomedical research to identify emerging scientific, technical, policy and organizational trends. It identifies common concerns and practices in the emerging community of computationally-oriented bio-scientists by reviewing a national symposium, Digital Biology: the Emerging Paradigm, held at the National Institutes of Health in Bethesda, Maryland, November 6th and 7th 2003. This meeting showed how biomedical computing promises scientific breakthroughs that will yield significant health benefits. Three key areas that define the emerging discipline of digital biology are: scientific data integration, multi-scale modeling and networked science. Each area faces unique technical challenges and information policy issues that must be addressed as the field matures. Here we summarize the emergent challenges and offer suggestions to academia, industry and government on how best to expand the role of computation in their scientific activities.     

Anything but Conventional Chromatography Approaches in Bioseparation

While packed bed chromatography, known as conventional chromatography, has been serving the biopharmaceutical industry for decades as the bioseparation method of choice, alternative approaches are likely to take an increasing leading role in the next few years. The high number of new biological drugs under development, and the need to make biopharmaceuticals widely accessible, has been driving the academia and industry in the quest of anything but conventional chromatography approaches. In this perspective paper, these alternative approaches are discussed in view of current and future challenges in the downstream processing field.     

Adapting immunity with subunit vaccines: case studies with group A Streptococcus and malaria

Although vaccines have widely been regarded as the most cost-effective way to improve public health, for some organisms new technological advances in vaccine design and delivery, incurring additional developmental costs, will be essential. These organisms are typically those for which natural immunity is either slow to develop or does not develop at all. Clearly, such organisms have evolved strategies to evade immune responses and innovative approaches will be required to induce a type of immune response which is both different to that which develops naturally and is effective. This article describes some approaches to develop vaccines for two such organisms (malaria parasites and Streptococcus pyogenes (group A Streptococcus)) that are associated with widespread mortality and morbidity, mostly in the poorest countries of the world. At this stage, the challenges are primarily scientific, but if these hurdles are surmounted then the challenges will become financial ones--developing much needed vaccines for people least able to afford them.     

Genome Elimination: Translating Basic Research into a Future Tool for Plant Breeding

During the course of our history, humankind has been through different periods of agricultural improvement aimed at enhancing our food supply and the performance of food crops. In recent years, it has become apparent that future crop improvement efforts will require new approaches to address the local challenges of farmers while empowering discovery across industry and academia. New plant breeding approaches are needed to meet this challenge to help feed a growing world population. Here I discuss how a basic research discovery is being translated into a potential future tool for plant breeding, and share the story of researcher Simon Chan, who recognized the potential application of this new approach—genome elimination—for the breeding of staple food crops in Africa and South America.

This article is part of the PLOS Biology Collection “The Promise of Plant Translational Research.”

     

Combination drugs, an emerging option for antibacterial therapy

The emerging and sustained resistance to antibiotics and the poor pipeline of new antibacterials is creating a major health issue worldwide. Bacterial pathogens are increasingly becoming resistant even to the most recently approved antibiotics. Few antibiotics are being approved by regulatory organizations, which reflects both the difficulty of developing such agents and the fact that antibiotic discovery programs have been terminated at several major pharmaceutical companies in the past decade. As a result, the output of the drug pipelines is simply not well positioned to control the growing army of resistant pathogens, although academic institutions and smaller companies are trying to fill that gap. An emerging option to fight such pathogens is combination therapy. Combinations of two antibiotics or antibiotics with adjuvants are emerging as a promising therapeutic approach. This article provides and discusses clinical and scientific challenges to support the development of combination therapy to treat bacterial infections.     

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.     

A blueprint for advancing genetics-based cancer therapy

In the era of next-generation sequencing, there are significant challenges to harnessing cancer genome information to develop novel therapies. Key research thrusts in both academia and industry will speed this transition, and lessons learned for cancer will more broadly shape the process for genetic contributions to the therapy of disease more broadly.     

Bactericidal,quorum quenching and anti-biofilm nanofactories: a new niche for nanotechnologists

Despite several conventional potent antibacterial therapies, bacterial infections pose a significant threat to human health because they are emerging as the leading cause of death worldwide. Due to the development of antibiotic resistance in bacteria, there is a pressing demand to discover novel approaches for developing more effective therapies to treat multidrug-resistant bacterial strains and biofilm-associated infections. Therefore, attention has been especially devoted to a new and emerging branch of science “nanotechnology” to design non-conventional antimicrobial chemotherapies. A range of nanomaterials and nano-sized carriers for conventional antimicrobial agents have fully justified their potential to combat bacterial diseases by reducing cell viability, by attenuating quorum sensing, and by inhibiting/or eradicating biofilms. This communication summarizes emerging nano-antimicrobial therapies in treating bacterial infections, particularly using antibacterial, quorum quenching, and anti-biofilm nanomaterials as new approaches to tackle the current challenges in combating infectious diseases.     

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.     

Genomics: Applications,Challenges, and Opportunities for the U.S. Environmental Protection Agency

Genomics information has great potential to enhance assessment of risks to human health and the environment. Although understanding genomic responses with respect to adverse ecological and human health outcomes is not, as yet, established, it is important to consider the likely future impacts of genomics technologies on risk assessment and decision-making. Four areas are identified as those likely to be influenced by the generation of genomics information within, and the submission of such information to, the U.S. Environmental Protection Agency (USEPA): risk assessment, prioritization of contaminants and contaminated sites, monitoring, and reporting provisions. For each of these risk assessment and regulatory applications, representative activities are presented to illustrate the application. Three major challenges for the USEPA associated with genomics are also identified in the areas of research, technical development, and capacity. The USEPA's initial activities to address these challenges are discussed. The Agency recognizes it must be prepared to use genomics information, and that many scientific, policy, ethical, and legal concerns will need to be addressed. The USEPA also recognizes it is essential to continue to collaborate with other federal agencies, academia, the regulated community, and other stakeholders in order to benefit from ongoing advances in genomics in the wider scientific and regulatory communities.     

ECVAM-ICCVAM: prospects for future collaboration

The level and complexity of testing for hazard and risk assessment of marketed products and environmental agents has increased substantially over time, resulting in the use of greater numbers of both animals and humans for testing. Today, industry and regulatory bodies worldwide face increasing pressures to demonstrate responsible utilisation of laboratory animals, to limit their use, and to employ alternative non-animal tests. Institutions have also been established to identify, encourage development of, conduct research on, and validate new, improved, and surrogate test methods that will reduce and replace animal use. Two such organisations are ECVAM and the Interagency Coordinating Committee for the Validation of Alternative Methods (ICCVAM). As the evolutionary changes occurring in the field of toxicology result in an unprecedented increase in the introduction of alternative methodologies, these will strain the capacities of such alternative methods institutions. That realisation is causing a shift in thinking and creating an impetus to seek approaches by which to collaborate and develop more-efficient operational procedures for the validation and regulatory acceptance of alternative methods. Similarities in objectives, functions, scientific standards, and commitment to the principles of validation and animal welfare support the value of a cooperative arrangement between ECVAM and ICCVAM, to minimise duplication of effort, maximise productivity, and influence the international adoption of alternative tests. Opportunities for ECVAM-ICCVAM collaboration are discussed, which illustrate the feasibility and potential benefits of such a partnership.     

Industry's challenge to academia: changing the bench to bedside paradigm

The need for interdisciplinary collaboration is arising as a result of accelerating advances in basic science, including massive research and development funding by both government and industry, which has spurred the so-called "nanotechnology revolution" and developments at the intersection of the life and physical sciences, increasing emphasis by federal research funding agencies on interdisciplinary and inter-institutional research and by market influences. A number of barriers presently limit the interaction between academics and industry, including the typically very time-consuming and slow pace of technology transfer, which is compounded in the case of interdisciplinary and inter-institutional licensing, as well as the natural, and understandable, antipathies that exist between academia and industry as a result of their differing missions and approaches to scientific discovery. Moreover, if mechanisms are not in place at the outset of an inter-university collaboration, then the transition of inventions to clinical applications can be fraught with additional complexities and barriers. Policies suggested by the National Nanotechnology Initiative offer a number of ideas for overcoming barriers to multidisciplinary and inter-institutional research and illustrate some of the ways in which academia can structure partnerships with industry that will not only provide needed funding for multidisciplinary and inter-institutional biomedical research in an era of diminishing federal resources, but may permit academia, on the one hand, and industry, on the other, to benefit from the strengths provided by the other without compromising either academia's or industry's basic missions.     

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.     

The development, regulation and use of biopesticides for integrated pest management

Over the past 50 years, crop protection has relied heavily on synthetic chemical pesticides, but their availability is now declining as a result of new legislation and the evolution of resistance in pest populations. Therefore, alternative pest management tactics are needed. Biopesticides are pest management agents based on living micro-organisms or natural products. They have proven potential for pest management and they are being used across the world. However, they are regulated by systems designed originally for chemical pesticides that have created market entry barriers by imposing burdensome costs on the biopesticide industry. There are also significant technical barriers to making biopesticides more effective. In the European Union, a greater emphasis on Integrated Pest Management (IPM) as part of agricultural policy may lead to innovations in the way that biopesticides are regulated. There are also new opportunities for developing biopesticides in IPM by combining ecological science with post-genomics technologies. The new biopesticide products that will result from this research will bring with them new regulatory and economic challenges that must be addressed through joint working between social and natural scientists, policy makers and industry.     

Molecular characterization of genetically-modified crops: Challenges and strategies

Molecular characterization lays a foundation for safety assessment and subsequent monitoring of genetically modified (GM) crops. Due to the target-specific nature, conventional polymerase chain reaction (PCR)-based methods cannot comprehensively detect unintended gene insertions, let alone unknown GM events. As more and more new developed GM crops including new plant breeding technology (NPBT) generated crops are in the pipeline for commercialization, alternative -omics approaches, particularly next generation sequencing, have been developed for molecular characterization of authorized or unauthorized GM (UGM) crops. This review summarizes first those methods, addresses their challenges, and discusses possible strategies for molecular characterization of engineered crops generated by NPBT, highlighting needs for a global information-sharing database and cost-effective, accurate and comprehensive molecular characterization approaches.     

Will genomics revolutionize antimicrobial drug discovery?

Utilizing genome sequence data from bacterial and fungal pathogens for the discovery of new antimicrobial agents has received considerable attention, both practical and critical, from the pharmaceutical and biotechnological communities. Although no new drugs derived from genomics-based discovery have been reported to be in a development pipeline, the utilization of genomics has revolutionized many aspects of drug discovery. The application, utility, opportunity, and challenges afforded by many of these new approaches are discussed.