Choosing a career in industry: An interview with Rachel Haurwitz.

Scientists often contemplate careers in academia versus the biotech industry. We spoke with Dr. Rachel Haurwitz about her career trajectory, being a female scientist in the biotech world, how research in academia compares to industry, and career advice for young scientists thinking about venturing outside of academia into this area.

In conversation with Nigel Scrutton.

Nigel Scrutton FRS is Professor of Molecular Enzymology and Biophysical Chemistry at the University of Manchester and former Director of the Manchester Institute of Biotechnology (MIB). He obtained a first degree in Biochemistry from King's College London and followed this with a PhD at the University of Cambridge. His doctoral research, undertaken in Richard Perham's laboratory, yielded fundamental breakthroughs in enzyme redesign that have stood the test of time. Nigel was awarded a ScD degree by the University of Cambridge in 2003. After faculty positions at the University of Leicester, Nigel was appointed Professor at the University of Manchester in 2005. Over the last 15 years, he has cemented his reputation as a world leader in the fields of enzyme engineering and biocatalysis, synthetic biology, biophysics and biomanufacturing, notably by establishing and directing the Synthetic Biology Research Centre 'SYNBIOCHEM' and UK Future Biomanufacturing Research Hub. In recognition of his scientific contributions, he has received many academic awards and accolades, including being elected as Fellow of the Royal Society earlier this year. In this interview, he highlights how fundamental studies of enzymatic catalysis and mechanisms are driving key advances in biotechnology and biomanufacturing, and describes how the experiences and mentors of his formative years helped to shape his successful career at the interface between discovery and application-focused science.

From conception to COVID-19: an arduous journey of tribulations of racism and triumphs.

Growing up in a densely wooded tropical forest enhanced my curiosity in plants and reading biography of Marie Curie profoundly influenced pursuit of my research career. Early in my career, I developed in vitro functional chloroplasts, capable of expressing foreign genes and this laid the foundation for the chloroplast genetic engineering field. Four decades of research has advanced chloroplast bioreactors for production of industrial enzymes or biopharmaceuticals by small or large companies. Because I experienced firsthand horrors of expensive vaccines or medicines, I devoted most of my career to develop affordable therapeutics. During this long journey, I suffered institutional racial discrimination but was rescued by several guardian angels. This biography gives readers a glimpse of tribulations and triumphs of my journey and recognizes important contributions made by my mentees.

Forty years of study on the thermostable ß-glycosidase from S. solfataricus: Production, biochemical characterization and biotechnological applications.

The aim of this paper is to make the point on the fortieth years study on the ß-glycosidase from Sulfolobus solfataricus. This enzyme represents one of the thermophilic biocatalysts, which is more extensively studied as witnessed by the numerous literature reports available since 1980. Comprehensive biochemical studies highlighted its broad substrate specificity for ß-d-galacto-, gluco-, and fuco-sides and also showed its remarkable exo-glucosidase and transglycosidase activities. The enzyme demonstrated to be active and stable over a wide range of temperature and pHs, withstanding to several drastic conditions comprising solvents and detergents. Over the years, a great deal of studies were focused on its homotetrameric tridimensional structure, elucidating several structural features involved in the enzyme stability, such as ion pairs and post-translational modifications. Several ß-glycosidase mutants were produced in the years in order to understand its peculiar behavior in extreme conditions and/or to improve its functional properties. The ß-glycosidase overproduction was also afforded reporting numerous studies dealing with its production in the mesophilic host Escherichia coli, Saccharomyces cerevisiae, Pichia pastoris, and Lactococcus lactis. Relevant applications in food, beverages, bioenergy, pharmaceuticals, and nutraceutical fields of this enzyme, both in free and immobilized forms, highlighted its biotechnological relevance.

30 Years of Biotherapeutics Development-What Have We Learned?

Since the birth of biotechnology, hundreds of biotherapeutics have been developed and approved by the US Food and Drug Administration (FDA) for human use. These novel medicines not only bring significant benefit to patients but also represent precision tools to interrogate human disease biology. Accordingly, much has been learned from the successes and failures of hundreds of high-quality clinical trials. In this review, we discuss general and broadly applicable themes that have emerged from this collective experience. We base our discussion on insights gained from exploring some of the most important target classes, including interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), IL-6, IL-12/23, IL-17, IL-4/13, IL-5, immunoglobulin E (IgE), integrins and B cells. We also describe current challenges and speculate about how emerging technological capabilities may enable the discovery and development of the next generation of biotherapeutics.

Current research into snake antivenoms, their mechanisms of action and applications.

Snakebite is a major public health issue in the rural tropics. Antivenom is the only specific treatment currently available. We review the history, mechanism of action and current developments in snake antivenoms. In the late nineteenth century, snake antivenoms were first developed by raising hyperimmune serum in animals, such as horses, against snake venoms. Hyperimmune serum was then purified to produce whole immunoglobulin G (IgG) antivenoms. IgG was then fractionated to produce F(ab) and F(ab')2 antivenoms to reduce adverse reactions and increase efficacy. Current commercial antivenoms are polyclonal mixtures of antibodies or their fractions raised against all toxin antigens in a venom(s), irrespective of clinical importance. Over the last few decades there have been small incremental improvements in antivenoms, to make them safer and more effective. A number of recent developments in biotechnology and toxinology have contributed to this. Proteomics and transcriptomics have been applied to venom toxin composition (venomics), improving our understanding of medically important toxins. In addition, it has become possible to identify toxins that contain epitopes recognized by antivenom molecules (antivenomics). Integration of the toxinological profile of a venom and its composition to identify medically relevant toxins improved this. Furthermore, camelid, humanized and fully human monoclonal antibodies and their fractions, as well as enzyme inhibitors have been experimentally developed against venom toxins. Translation of such technology into commercial antivenoms requires overcoming the high costs, limited knowledge of venom and antivenom pharmacology, and lack of reliable animal models. Addressing such should be the focus of antivenom research.

History, Current State, and Emerging Applications of Industrial Biotechnology.

The past 150 years have seen remarkable discoveries, rapidly growing biological knowledge, and giant technological leaps providing biotechnological solutions for healthcare, food production, and other societal needs. Genetic engineering, miniaturization, and ever-increasing computing power, in particular, have been key technological drivers for the past few decades. Looking ahead, the eventual transition from fossil resources to biomass and CO2 demands a shift toward a 'bio-economy' based on novel production processes and engineered organisms.

Development of thin-layer cascades for microalgae cultivation: milestones (review).

In this work, the key moments of the development of the so-called thin-layer cascades (TLC) for microalgae production are described. Development started at the end of the 1950s when the first generation of TLCs was set-up in former Czechoslovakia. Since, similar units for microalgae culturing, which are relatively simple, low-cost and highly productive, have been installed in a number of other countries worldwide. The TLCs are characterized by microalgae growth at a low depth (< 50 mm) and fast flow (0.4-0.5 m/s) of culture compared to mixed ponds or raceways. It guarantees a high ratio of exposed surface to total culture volume (> 100 1/m) and rapid light/dark cycling frequencies of cells which result in high biomass productivity (> 30 g/m2/day) and operating at high biomass density, > 10 g/L of dry mass (DW). In TLCs, microalgae culture is grown in the system of inclined platforms that combine the advantages of open systems-direct sun irradiance, easy heat derivation, simple cleaning and maintenance, and efficient degassing-with positive features of closed systems-operation at high biomass densities achieving high volumetric productivity. Among significant advantages of thin layer cascades compared to raceway ponds are the operation at much higher cell densities, very high daylight productivities, and the possibility to store the culture in retention tanks at night, or in unfavourable weather conditions. Concerning the limitations of TLCs, one has to consider contaminations by other microalgae that limit cultivation to robust, fast-growing strains, or those cultured in selective environments.

Sarah-Maria Fendt: Driving scientific discovery through collaboration.

Sarah-Maria Fendt is a principal investigator at the Flemish Institute for Biotechnology (VIB) in Belgium, and her laboratory focuses on cellular metabolism and metabolic regulation. Recent work from Sarah's laboratory has shown that pyruvate available in the metastatic niche enables cancer cells to shape their environment and promote metastatic outgrowth. We contacted Sarah to find out more about her journey in science so far.

LeRoy Walters's Legacy of Bioethics in Genetics and Biotechnology Policy.

LeRoy Walters was at the center of public debate about emerging biological technologies, even as "biotechnology" began to take root. He chaired advisory panels on human gene therapy, the human genome project, and patenting DNA for the congressional Office of Technology Assessment. He chaired the subcommittee on Human Gene Therapy for NIH's Recombinant DNA Advisory Committee. He was also a regular advisor to Congress, the executive branch, and academics concerned about policy governing emerging biotechnologies. In large part due to Prof. Walters, the Kennedy Institute of Ethics was one of the primary sources of talent in bioethics, including staff who populated policy and science agencies dealing with reproductive and genetic technologies, such as NIH and OTA. His legacy lies not only in his writings, but in those people, documents, and discussions that guided biotechnology policy in the United States for three decades.

Between mice and sheep: Biotechnology, agricultural science and animal models in late-twentieth century Edinburgh.

In this paper, we investigate the ways in which a group of scientists in Edinburgh worked across mice and sheep during the last quarter of the twentieth century. With this local episode, we show the utility of an interspecies perspective to investigate recent historical transformations in the life sciences. We argue that the emergence of animal biotechnology was the result of interactions between neoliberal policymakers, science administrators, molecular biologists, agricultural breeders, and the laboratory and farm organisms with which they worked. During the early 1980s, all these actors believed that the exportation of genetic engineering techniques from mice to farm animals would lead to more effective breeding programmes in the agricultural sciences. However, the circulation of people, money, expertise and infrastructures that the experiments required, as well as the practical constraints of working with mice and sheep, resisted a simple scaling-up from one organism to the other. This displaced the goals of the Edinburgh scientists from the production of transgenic sheep to stem cell research and human regenerative medicine. We account for this unexpected shift by looking at the interplay between science policy and its implementation via collective action and bench work across different organisms. The emergence of animal biotechnology in Edinburgh also provides historiographical insights on the birth of Dolly the sheep and, more generally, on the interactions between the molecular and the reproductive sciences at the fall of the twentieth century.

Recent Patents Applications in Red Biotechnology: A Mini-Review.

BACKGROUND: The different fields of biotechnology can be classified by colors, as a "rainbow" methodology. In this sense, the red biotechnology, focused on the preservation of health, has been outstanding in helping to solve this challenge through the provision of technologies, including diagnostic kits, molecular diagnostics, vaccines, innovations in cancer research, therapeutic antibodies and stem cells. OBJECTIVE: The main goal of this work is to highlight the different areas within the red Biotechnology. In this sense, we revised some patents regarding red biotechnology as examples to cover this subject. METHODS: A literature search of patents was performed from the followings Patents Database: INPI, USPTO, Esp@cenet, WIPO and Google Patents. RESULTS: Our analysis showed the following numbers from patents found: cancer research (8), diagnosis kit (9), vaccines (8), stem cells (9) and therapeutic antibodies (5), where the United States is the leader for most filled patents in Red Biotechnology. CONCLUSION: This mini-review has provided an update of some patents on Recent Patents in Red Biotechnology. As far as we know, this is the first mini-review report on Red Biotechnology based on patents.

[Monoclonal antibodies at the forefront of health care economic analyses]. / Les anticorps monoclonaux à l'aune de l'économie de la santé - Les accords de l'industrie pharmaceutique.

Therapeutic antibodies have been used for several decades and their associated market (project numbers, approvals…) continues to grow. Remarkably, a new threshold was crossed in the early 2010's to make this decade the decade of immunotherapy. Over the past 10 years, 62 antibodies have been approved, the number of annual transactions between stakeholders has increased to more than 300 (three times more in 2018 than in 2009). The revolution of immunotherapy in cancer treatment and the recent use of antibodies as first-line treatment are the major turning points in oncology. Thus, the last three years alone represent two thirds of the most important deals of the decade involving immunotherapies. Immunotherapy is currently experiencing a golden age that has resulted in many successes, especially in France where biotechnology companies and large pharmaceutical companies have achieved impressive therapeutic and financial results.

TITLE: Les anticorps monoclonaux à l'aune de l'économie de la santé - Les accords de l'industrie pharmaceutique. ABSTRACT: Bien que les anticorps thérapeutiques existent depuis maintenant plusieurs décennies et que le marché associé (nombre de projets en développement, nombre d'anticorps mis sur le marché…) soit en croissance, un palier a été franchi au début des années 2010 pour faire de cette décennie celle de l'immunothérapie. Pendant ces 10 dernières années, 62 anticorps ont obtenu une autorisation de mise sur le marché et le nombre d'accords (acquisitions, participations, partenariats) annuels entre les différents acteurs a dépassé la barre des 300 (avec trois fois plus d'accords en 2018 qu'en 2009). La révolution de l'immunothérapie dans le traitement des cancers et la récente utilisation d'anticorps en première ligne thérapeutique dans celui-ci sont les tournants majeurs de l'oncologie. Les trois dernières années (2016-2019) regroupent d'ailleurs à elles seules les deux tiers des plus importants accords de la décennie impliquant des immunothérapies. L'immunothérapie connaît donc actuellement un âge d'or qui se traduit par de nombreuses success stories, notamment en France, où sociétés de biotechnologie et big pharma présentent des résultats très positifs au plan tant thérapeutique que financier.